Patent Publication Number: US-8113196-B2

Title: Dispensing device

Description:
BACKGROUND OF THE INVENTION 
     1. Field of Invention 
     The present invention relates to a dispensing device for dispensing a preferably medical formulation, in particular containing or consisting of a drug or mixture of drugs. 
     2. Description of Related Art 
     Drugs delivered through dispensing devices, in particular inhalers, are intended to optimally target specific sites in the pulmonary system. These sites include the nasal passages, the throat, and various locations within the lungs, such as the bronchi, bronchioles and alveolar regions. The ability to deliver drugs to a target area depends inter alia on the aerodynamic sizes of the particles or droplets. As currently believed to be understood, particles having an aerodynamic diameter of less than 2 micrometer are considered to be potentially optimal for deposition in the alveolar region of the lung. Particles that have an aerodynamic diameter of between 2 and approximately 5 micrometer may be more suitable for delivery to the bronchiole or bronchi regions. Particles with an aerodynamic size range greater than 6 micrometer, and more preferably 10 micrometer, are typically suitable for delivery to the laryngeal region, throat or nasal passages. 
     In most cases, it is desired to achieve a high inhalable fraction and a high delivery efficiency, i.e., the fraction of the initial dose of drug that reaches the desired region, in particular in the lung. This depends on various factors, in particular on the characteristics of the generated spray plume, such as propagation velocity of the plume, particle size and its distribution, fraction of small particles, fraction of gas or the like. In the present invention, the desired spray plume characteristics include preferably a small particle size, a high fraction of drug particles with a diameter of 6 micrometer or less, a low propagation velocity and/or a long duration of spray generation and possible inhalation. 
     Most powder inhalers are of the passive type where the powder is inhaled by the patient without the aid of an additional energy source. The problem with passive inhalers is that the inhalable fraction, or the proportion of powder that actually enters the lungs, is largely dependent on the breathing of the patient. The transfer and de-agglomeration of the powder and hence the inhalable fraction is a function of the flow rate of inhaled air through the device and, therefore, varies greatly from patient to patient. 
     Dry powder inhalers are subdivided into single dose and multi-dose devices or inhalers. Multi-dose inhalers are further subdivided into pre-metered types where the doses are stored individually and into metering inhalers where each powder dose is metered in the device. 
     Multi dose pre-metered inhalers have the advantage that the single doses are metered under strict factory conditions and the powder can quite easily be isolated from the atmosphere. In many applications the active drug powder is mixed with a carrier such as lactose. The lactose and/or active drug(s) tend to absorb humidity from the atmosphere, which makes them stick together and difficult to transfer and de-agglomerate. 
     The present invention relates in particular to an active, gas (preferably air) powered, pre-metered multi-dose dispensing device for dispensing a formulation containing or consisting of a drug, such as a dry powder inhaler. 
     U.S. Pat. No. 4,627,432 A discloses a device for administering medicaments to patients, namely an inhaler. The inhaler comprises a disk-like blister pack having a plurality of blister pockets arranged in a circle. Each blister pocket contains a dose of the powder. A plunger can open a blister pocket. When a blister is opened, the medicament can be withdrawn by a patient inhaling through a mouthpiece. 
     International Patent Application Publication 2005/002654 A2 discloses a passive device for dispensing individual doses of powder. The doses are contained in respective pockets of a disc-shaped carrier and opened by outwardly rupturing a lidding foil in axial direction by means of pressure on an opposite side surface. The pockets are moveable in axial direction into an airstream generated by breathing of a patient for dispensing a dose of powder from the pocket. The device provides individual respective deaggregation flow paths for each pocket, split airstreams allowing improved entrainment of powder, a cam mechanism for outwardly rupturing the pockets, an indexing mechanism linked to the cam mechanism, and a dose counter. 
     It is difficult to empty the respective pocket completely during a dispensing operation. Incomplete emptying results in decreased delivery efficiency. Some powder may be lost in the inhaler and not dispensed because the known solutions require relatively long paths for the powder until the powder reaches a nozzle and is actually dispensed. This might reduce the delivery efficiency further. In addition, de-agglomeration of the powder is difficult. 
     International Patent Application Publication WO 2006/037636 A2 discloses an active dispensing device with an air pump for dispensing powder separately from storage chambers in a common carrier. Preferably, an individual deaggregation and outlet duct having a flat cross-section is associated to each storage chamber. 
     SUMMARY OF THE INVENTION 
     The present invention relates to the dispensing of a preferably medical formulation. The term “formulation” relates in particular to powder, but may include or relate to liquid as well. Consequently, the fine “particles” may be either solid or liquid. The term “liquid” has to be understood preferably in a broad sense covering inter alia solutions, suspensions, suslutions, mixtures thereof or the like. More particularly, the present invention relates to the dispensing of formulations for inhalation, such as medical formulations containing or consisting of at least one drug. 
     In the following, the description will focus mainly on powder formulations. However, the same applies for liquid formulations. 
     In particular, the present invention is concerned with dry powder inhalers for the delivery of drugs to the lungs. Many dry powder inhalers are on the market or have been proposed. There are two main types, namely the passive ones and the active ones. In passive inhalers all the energy required for de-agglomerating the powder and transferring the powder to the lungs is provided by the breathing of a user, respectively the patient. In active inhalers there is an additional source of energy to help to transfer and de-agglomerate the powder. 
     A primary object of the present invention is to provide an improved dispensing device, in particular wherein a compact construction, easy handling or operation, a high delivery efficiency and/or desired spray plume characteristics can be achieved. 
     According to the present invention, the dispensing device or storage device comprises means for limiting the movement of the inserts. This allows a compact and simple construction and easy handling or operation. 
     The above object is achieved by a dispensing device for dispensing a formulation as a spray, wherein the dispensing device is adapted to receive or comprises a storage device with multiple separate and pre-metered doses of the formulation in receptacles that, preferably, are annularly arranged, each receptacle comprising a moveable insert with a respective dose of formulation, and wherein a means for reinserting the inserts into the respective receptacles after use is provided. 
     According to another aspect of the present invention, an actuator, in particular a grip, of the dispensing device is radially movable or operable to rotate the storage device to the next receptacle and/or to radially move the connecting element in order to individually open the respective receptacle and/or to connect a gas supply or pump to the respective receptacle and/or to push an insert out of the respective receptacle. This allows a compact construction and/or easy handling or operation. 
     Another preferred aspect of the present invention is that the dispensing device comprises a means for preventing a backstroke of the connecting element during dispensing. This allows easy handling or operation and ensures high delivery efficiency and/or desired spray plume characteristics. 
     According to a further preferred aspect of the present invention, the dispensing and storage device comprise means for aligning the connecting element and the respective receptacle, wherein said means comprise guiding portions formed at or by the storage device and/or the receptacles. This ensures correct alignment and, thus, the desired dispensing with high delivery efficiency and/or desired spray plume characteristics, wherein compact construction and easy handling or operation are possible. 
     According to a further preferred aspect of the present invention, the dispensing device comprises means for reinserting the inserts into the respective receptacles after use. This allows a compact and simple construction and/or easy handling or operation. 
     According to another further aspect of the present invention, the storage device comprises a common carrier, wherein the receptacles are separate parts mounted on the carrier by clipping, snapping, pressing and/or clamping. This allows a compact and simple construction and, in particular, an optimized filling of the receptacles, preferably of inserts of the receptacles, with the dosed formulation. 
     According to another preferred aspect of the present invention, the storage device comprises an empty or hollow or dummy receptacle into which the connecting element can engage in a state before first use or when mounting the dispensing device. This allows a compact and simple construction and, in particular, facilitates mounting of the dispensing device. 
     According to a further preferred aspect of the present invention, the dispensing device comprises multiple, in particular three, life span blocking means. In particular, the blocking means are at least partly formed by the storage device, preferably by a common carrier supporting multiple receptacles of the storage device. This allows a compact and simple construction and/or easy and secure handling and operation. 
     According to another preferred aspect of the present invention, the storage device comprises inserts that are moveable within respective cavities or receptacles for dispensing, wherein each insert comprises a tip portion or other opening means and/or is tapered in order to facilitate opening of an associated seal by movement of the respective insert against or through the seal. This allows a compact and simple construction and/or easy and secure handling and operation. 
     According to a further preferred aspect of the present invention, the dispensing device comprises detection means for detecting inhalation or breathing in and/or trigger means for triggering dispensing of the respective dose by means of pressurized gas. This allows easy and simple handling and operation. 
     Preferably, each insert comprises at least one channel and/or nozzle arrangement in order to directly form the spray during use. Thus, the spray is generated by the respective insert when pressurized gas is supplied. This makes it possible to respectively generate sprays with the desired spray plume characteristics with high accuracy. 
     Further aspects, advantages and features of the present invention will be apparent from the following detailed description of preferred embodiments in conjunction with the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic sectional view of a dispensing device with a storage device according to one embodiment of the present invention during dispensing; 
         FIG. 2  is a schematic section of the storage device with an insert; 
         FIG. 3  is a schematic sectional view of the insert; 
         FIG. 4  is a schematic sectional view of the insert taken along line IV-IV of  FIG. 3 ; 
         FIG. 5  is a schematic sectional view of another insert; 
         FIG. 6  is a schematic sectional view similar to  FIG. 4  of the insert, but taken along line VI-VI of  FIG. 5  and with a carrier and an inserted piercing element; 
         FIG. 7  is a schematic perspective view of a dispensing device according to a further embodiment of the present invention; 
         FIG. 8  is a schematic view of inner components of the dispensing device according to  FIG. 7  with retracted air assembly; 
         FIG. 9  is a schematic view of inner components of the dispensing device according to  FIG. 7  with advanced air assembly in an activated state; 
         FIG. 10  is a schematic view of inner components of the dispensing device according to  FIG. 7  with advanced air assembly after dispensing; 
         FIG. 11  is a schematic view of a receptacle of a storage device; 
         FIG. 12  is a schematic view of a carrier of the storage device; 
         FIG. 13  is a partial enlarged view of the carrier according to  FIG. 12 ; 
         FIG. 14  is another partial enlarged view of the carrier according to  FIG. 12 ; 
         FIG. 15  is a schematic perspective view of a needle holder of the air assembly; 
         FIG. 16  is a schematic, partially sectional perspective view of the dispensing device according to  FIG. 7  with a pulled grip; and 
         FIG. 17  is a schematic view of a half of the housing of the dispensing device according to  FIG. 7 . 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     In the figures, the same reference signs are used for the same or similar parts and components, wherein preferably the same or similar features, aspects and/or advantages are achieved in the different embodiments, even if a repetition of the respective description is omitted. 
       FIG. 1  shows in a schematic sectional view—for illustration purposes not in scale—a dispensing device  1  according to the present invention. The dispensing device  1  is preferably an active device, in particular gas powered. Preferably, the dispensing device  1  is an oral or nasal inhaler, in particular, a dry powder inhaler, for a user, respectively, the patient (not shown). 
     Preferably, the dispensing device  1  is portable and/or hand-held. 
     The dispensing device  1  may be used for dispensing any formulation  2  as defined in the introductory part of the description. In particular, a medical formulation  2  or a formulation  2  for inhalation will be used. The formulation  2  preferably contains or consists of at least one drug. When the formulation  2  is dispensed, a spray  3  is generated as indicated in  FIG. 1 . The spray  3  includes or consists of fine particles (solid and/or liquid) and preferably has the desired spray plume characteristics. 
     The formulation  2  may be a liquid, in particular a solution, a suspension or any mixture thereof, i.e., a so-called suslution. Preferably, when different drugs are dispensed simultaneously, a suslution may be used. The principle of the suslution is based on that different drugs may be combined in one formulation simultaneously as a solution and as a suspension. In this respect, reference is made to European Patent Application EP 1 087 750 A1, which is incorporated herein as additional disclosure in this respect. 
     Preferably, the formulation  2  is a powder. The powder may be a pure drug or a mixture of at least two drugs or any other mixture of at least one drug. In addition, the powder may contain at least one other material, in particular a drug carrier such as lactose. In the following, the description focuses on powder as formulation  2 . However, this applies in a similar manner if a liquid formulation  2  is used. 
     Preferably the mean diameter of the powder particles is about 2 to 7 micrometer, in particular 6 micrometer or less. This applies in particular if the powder does not contain any drug carrier such as lactose. 
     If the powder contains a drug carrier, such as lactose, and at least one drug, the powder  2  may have a particle size of 20 to 300 micrometer, in particular about 30 to 60 micrometer. However, the de-agglomeration, which will be described later in more detail, may result even in this case in a spray  3  with a smaller particle size, e.g., of about 10 micrometer or less. In particular, the drug may be separated from the drug carrier during de-agglomeration so that primarily the drug will be inhaled due to its small particle size of about 2 to 6 micrometer and the larger drug carrier will be swallowed when using the dispensing device as an inhaler. Alternatively or additionally, breaking or opening of the drug carrier is possible during de-agglomeration. 
     The diameters mentioned above and below may be understood as mass medium aerodynamic diameters and/or may apply to the particle size or a fraction of the particles of the spray  3 . 
     Preferably, the formulation  2  is premetered in separate or individual doses, which can be discharged one after the other by the dispensing device  1 , in particular, for inhalation. 
     The dispensing device  1  is adapted to receive or comprises a storage device  4  for storing preferably multiple and pre-metered doses of the formulation  2 . The storage device  4  may be integrated into the dispensing device  1  or form part of the dispensing device  1 . Alternatively, the storage device  4  may be a separate part that can be inserted or connected with the dispensing device  1  and optionally replaced. 
       FIG. 2  shows a schematic cross-section of the preferably ring-like storage device  4 . 
     The storage device  4  preferably comprises a carrier  5  and at least one insert  6 , preferably multiple inserts  6 . In particular, the carrier  5  may comprise or support 20 to 100 inserts, but preferably 30 to 60 inserts  6 . Each insert  6  preferably contains one pre-metered dose of the formulation  2 . However, each insert  6  may also contain more than one formulation  2 , i.e., different formulations  2 . Additionally or alternatively, different inserts  6  may contain different formulations. In context of the present invention, “different” means, in particular, that the formulations  2  differ in at least one of the composition, the drug, the dose or amount, the concentration, and consistence of the formulation  2 , e.g., liquid or dry powder. 
     The storage device  4  or carrier  5  preferably comprises multiple cavities  7  or receptacles for receiving or containing the inserts  6 . In particular, each insert  6  is located in a separate cavity  7 . Preferably, the cavities  7  are separate from each other, and in particular, are sealed relative to each other. 
     In the present embodiment, each cavity  7  comprises at least one opening  8 , in particular two preferably opposed openings  8  (here, at the radially inner and outer circumference or periphery). 
     The cavities  7  or its openings  8  are covered by respective covers or seals  9  which are preferably formed by heat-sealed foils on opposite sides of the respective cavity  7  or the carrier  5 . In the present embodiment, the seal  9  is in particular metallic foil, such as aluminum foil, plastic foil, a multi-layer arrangement or the like. The seal  9  preferably protect the inserts  6  and/or formulation  2  against humidity, dirt, moisture and/or the like. The seals  9  are respectively resistant and/or impermeable, in particular gas-tight. 
     In this preferred embodiment, the storage device  4  or carrier  5  is ring-like and the cavities  7  extend at least substantially in radial direction. The cavities  7  are distributed around the perimeter of or along the storage device  4  or carrier  5 , preferably equally spaced relative to the adjacent cavities  7 . 
     In the present embodiment, the storage device  4 /carrier  5  is preferably rotatable around axis “A” shown in  FIG. 1 . In particular, the dispensing device  1  can be opened and the storage device  4 /carrier  5  can be inserted or replaced. 
     The carrier  5  may be a molded element, a ring, a strip, a cartridge, a blister or a container. Preferably, the storage device  4  or carrier  5  is rigid or at least essentially stiff. 
     Preferably, the carrier  5  is made of foil, plastic, ceramic and/or composite material, in particular, of thermoplastics or thermoplastic elastomer. 
     Each cavity  7  or receptacle preferably forms a guide for the associated insert  6 , in particular so that the insert  6  is moveable in at least or only one direction and/or at least or only partially out of the cavity  7  or receptacle. 
       FIG. 1  shows a situation, where the insert  6  on the right side has already been pushed partially out of its associated cavity  7  and/or the outer opening  8  and/or through the respective seal  9  of its associated cavity  7  for opening the seal  9 . The insert  6  shown on the left side of  FIG. 1  is still within its closed and sealed cavity  7 . 
     Each insert  6  is preferably produced filled with the respective dose of formulation  2  separately from the storage device  4  or carrier  5  and, then, inserted into its respective cavity  7  or receptacle. 
     Preferably, each insert  6  is molded and/or made of foil, plastic, ceramic and/or composite material, in particular of a thermoplastic or thermoplastic elastomer and for seals of an elastomer or silicone. 
     According to a preferred embodiment, the carrier  5  and/or the inserts  6  are made of at least one of the following materials or any mixture or blend thereof: ABS (acrylonitril-butadiene-styrene copolymer); SAN (styrene-acrylonitril-copolymer); PBT (polybutylene terephthalate); PC (polycarbonate); CA (cellulosic acetate); EVA (ethylene vinylacetate copolymer); PA (polyamide); PE (polyethylene); PP (polypropylene); PMMA (polymethylmethacrylate); POM (polyoxymethylene, polyacetal); PPS (polyphenylene sulfide); PS (polystyrene); PBTP (polybutylene terephthalate); TPU (thermoplastic polyurethane); blend of PC and PBTP; blend of PC and ABS; LCP (liquid crystal polymers); PHCS (polypyrrolor polythiophene); PPA (polyphthalamide); PSU (polysulfone); PTFE (polytetrafluorethylene); PUR (polyurethane); SB (styrene-butadiene copolymer); PIB (polyisobutylene); PAN (peroxyacyInitrate); PET (polyethylene terephthalate); AMMA (acrylonitril-methymethacrylat copolymer); PAR (polyarylate); PEEK (polyetheretherketone); COC (cycloolefine copolymer). 
     Each insert  6  may form a preferably block-like unit and/or be rigid. Alternatively, the inserts  6  may be flexible. In particular, each insert  6  may be a unitary unit or consists of multiple elements. In particular, the insert  6  forms one component or is made of one piece. Each insert  6  may be a molded element, a cartridge, a blister, a capsule, a container or the like. 
     In the following, a preferred construction of one insert  6  is explained. Preferably, all inserts  6  are identical. However, it is also possible that the (all or some) inserts  6  are different. For example, two or more groups of different inserts  6  can be provided. It is possible that one group has a different dose or different formulation  2  than the other group. For example, the inserts  6  of the different groups could be arranged alternately one after the other so that a patient or user may use for example each morning an insert  6  of one group and each evening an insert  6  of the other group. 
     Each insert  6  preferably comprises a storage chamber  10  for a single dose of the formulation  2 . The schematic sectional view according to  FIGS. 2 and 3  and the schematic sectional view according to  FIG. 4  along line IV-IV of  FIG. 3  show one preferred embodiment of the insert  6 . The insert  6  comprises a storage chamber  10  for the formulation  2 . In the present embodiment, the storage chamber  10  is preferably formed in a molded base member  11  of the insert  6 . 
     The insert  6 /base member  11  further comprises a duct  12  or the like for deagglomerating and/or discharging the formulation  2  during the dispensing operation. The formulation  2  is dispensed through the duct  12  during the dispensing operation, in particular for de-agglomerating the powder and/or forming the spray  3 . 
     Preferably, the duct  12  is flat and/or rectangular in cross section. In particular, the cross section corresponds to a hydraulic diameter of less than 1 mm. In particular, the duct  12  is designed as described in International Patent Application Publication WO 2006/037636 A2, which is incorporated by reference. 
     According to another (unillustrated) embodiment, the duct  12  can also be used as a reservoir (storage chamber  10 ) for the formulation  2 . In this case, the separate storage chamber  10  is not required. Then, the duct  12  is designed to enable sufficient mixing of the gas with the formulation  2  and sufficient de-agglomeration of the powder formulation  2 . 
     Preferably, the spray  3  having its desired spray characteristics is directly ejected or discharged from the insert  6 /duct  12 . 
     As noted above, the insert  6  is formed as a unitary component or is made of one piece. The insert  6  or duct  12  can comprise a nozzle arrangement  13  preferably at an outlet  15  or end of duct  12  or formed by duct  12 , as shown in the schematic longitudinal sectional view of another embodiment according to  FIG. 5 . 
     Preferably, the storage chamber  10  and/or the duct  12 /nozzle  13  is formed by or in the base member  11 , in particular by a recess, groove or the like in the base member  11  and by an associated cover member  14  as shown in  FIG. 4 . In particular, the duct  12  forms a channel from the storage chamber  10  to the outlet  15  of the insert  6  in particular for directly discharging or dispensing the formulation  2  as spray  3  as shown in  FIG. 1 . Preferably, the base member  11  is molded and/or rigid. Preferably, the cover member  14  is rigid and/or welded to the base member  11 . 
     It is noted that the inserts  6  may be or are preferably open, i.e., not sealed, in particular, at their respective outlet  15  only since experiments have shown that seal of the carrier  5 /the cavity  7  is sufficient. The duct  12 /nozzle arrangement  13  is preferably so small in cross section or provided with a bursting element or any other suitable means that insures that the formulation  2  is not discharged, even with opened seal  9  and/or during strong shaking of the dispensing device  1 /storage device  4 , but only when gas (air) is forced through the insert  6  and duct  12 . 
     The storage device  4  may comprise only one insert  6  with one storage chamber  10  for a single dose or can be provided with multiple storage chambers  10  with different formulations  2 . In the preferred embodiment, each insert  6  is for single dose and/or use only, but the storage device  4  preferably comprises multiple inserts  6 , and thus, contains multiple doses of the formulation  2 , which can be dispensed subsequently. 
     Further, the inserts  6  and cavities  7  are preferably adapted to each other such that the seals  9  contact end faces of the inserts  6 , and thus, cover the outlets  15 . This may (further) prevent any formulation  2  from dissipating through the duct  12 /outlet  15  before the desired dispensing. In order to increase the seal or cover effect of seal  9 , the inserts  6  may be slightly longer than the cavities  7  and/or protrude at its outlet side and/or be pressed with their outlets  15  against the seals  9  or vice versa. 
     Preferably, the nozzle arrangement  13  forms a means for slowing down the velocity as shown in the embodiment of  FIG. 5 . This means forms here a multiple jet impinging means. The means forms multiple—at least two—jets P which impinge, i.e., hit each other, as indicated in  FIG. 5 . In this embodiment, the duct  12  divides into two sections  12   a ,  12   b  that are designed such that the openings or outlets  15  are inclined relative to each other so that the jets P ejected from the sections  12   a ,  12   b  are angled toward each other so as to impinge. For example, a flow divider  11   a  or any other guiding means can be located in the flow path to form the at least two sections and/or last sections  12   a ,  12   b  of the duct  12  as shown in  FIG. 5 . 
     The embodiment according to  FIG. 5  is also suitable for impinging more than two jets P. For example, it is possible to have similar arrangements in the cross sectional planes perpendicular to the drawing plane resulting in four outlet directions and jets P arranged on the surface of a conus. However, multiple other arrangements with similar effects are possible. 
     The impinging angle W between the jets P is between 30 and 180 degrees, preferably at least 90 degrees for powder, in particular, about 90 to 150 degrees. 
     The impinging of the jets P results in a decrease of the velocity of the spray  3  and/or in a de-agglomeration of the powder or forming of small droplets and/or in separation of drug particles from a carrier and/or in better focusing of the spray  3 . These effects depend on the impinging angle W. A larger impinging angle W tends to result in better effects. In contrast to liquid jets, an impinging angle W of 90 degrees or more is possible and preferred for powder. 
     Alternatively, the nozzle  13  or any other suitable nozzle arrangement could be used instead of or in any other combination with duct  12 . 
       FIG. 6  shows a schematic sectional view of the insert  6  along line VI-VI of  FIG. 5 , wherein the insert  6  is housed in its cavity  7 /storage device  4 , but already moved somewhat outward of one opening  8 . 
     The insert  6  preferably has an inlet for supplying preferably pressurized gas into the storage chamber  10  to force the formulation  2  through the duct  12 /nozzle arrangement  13  and directly generate the described spray  3 . In the present embodiment, the inlet is preferably formed by a weak or thinned portion and/or is designed as a preferably tube-like recess  16  or blind bore formed in the base member  11 . Preferably, the recess  16  is not directly connected to the storage chamber  10 , but is separated by a seal or an intermediate or thinned wall or the like. This wall can be penetrated e.g., by a piercing element  17  such as a needle as shown schematically in  FIG. 6  or by any other suitable opening, connecting and/or supply means, in particular when the respective insert  6  is connected to a gas supply as explained in the following. Preferably, the piercing element  17  is a hollow needle with a solid or closed tip  17   a  and a side opening  17   b  adjacent the tip  17   a  for supplying the pressurized air into the insert  6 /storage chamber  10 . 
     In the present invention, the expression “piercing element  17 ” preferably covers also all other suitable types of means for opening and/or connecting the storage device  4 , the carrier  5 , a cavity  7  and/or an insert  6  and/or for directly or indirectly supplying gas to an insert  6  or its respective storage chamber  10 . 
     It is noted that the cross sections of the inserts  6  and the cavities  7  are preferably polygonal, in particular rectangular or that other guiding means are preferably provided, in order to avoid that the inserts  6  rotate within the cavities  7 . However, if the inserts  6  are rotatably symmetrical with respect to the recess  16  or any other connection/inlet for gas supply and with respect to its outlet  15 , the inserts  6  may also be cylindrical and/or can rotate within the cavities  7 . This may facilitate insertion of the inserts  6  into the cavities  7  during production. 
     The duct  12  is preferably at least tangentially connected to the storage chamber  10  as shown in  FIGS. 3 &amp; 5 . Preferably, the duct  12  is connected at one axial end of the preferably cylindrical chamber  10 , and the gas inlet (recess  16 /piercing element  17 ) is connected or connectable to the other axial end of the chamber  10  as indicated in  FIG. 6 . In particular, the gas inlet is connected also tangentially to the storage chamber  10 , such that swirls are generated by the entering gas with a swirl direction supporting discharge of the mixture of gas and formulation  2  through the duct  12 , which connects tangentially to the rotational direction of the swirl. 
     The dispensing device  1  uses preferably pressurized gas, in particular air, to force the formulation  2  through the duct  12 /nozzle arrangement  13  to de-agglomerate the powder and/or to generate the spray  3  with fine powder particles. Preferably, the dispensing device  1  comprises a means for providing pressurized gas, in the present embodiment an air pump  18 , as indicated in  FIG. 1 , which can preferably be actuated or operated manually, e.g., as indicated by a handle or actuator  19  and/or by a spring means as shown later in another embodiment. In particular, the air pump  18  comprises or is formed by a bellows. But, it could also be a piston-cylinder-arrangement. Instead of the air pump  18 , the means for providing pressurized gas can be e.g., a capsule, container or the like containing pressurized or liquefied gas for powering the dispensing device  1 , i.e., dispensing the formulation  2  as desired. Therefore, the term “means for pressurizing gas” is to be understood in a broad sense to cover these and similar alternatives to the pump  18  as well. 
     The means for providing pressurized gas/air pump  18  may provide a gas pressure of less than 300 kPa, in particular about 50 to 200 kPa. This is preferably sufficient for operating the dispensing device  1 . If liquefied gas or a container with pressurized gas is used, the gas pressures might range from 100 kPa to about 700 kPa. Then, the pressure may be reduced or throttled to the preferred pressure range before supplying the gas to the storage device  4 , in particular the storage chamber  10  of the respective insert  6 . 
     Preferably, all pressure values mentioned in the present description are gauge pressures, i.e., pressure differences. All pressure values relate to the pressure in a gas storage such as a container with pressurized or liquefied gas or provided by air pump  18  or relate to the pressures acting in the chamber  10  and/or in the duct  12 . 
       FIG. 1  shows that the dispensing device  1  preferably comprises a mechanism  20  for individually opening the cavities  7 , for individually moving the inserts  6 , preferably radially (here outwardly) and/or through an associated opening  8  and/or seal  9 , and/or for individually connecting the inserts  6  to the gas supply, in particular to the air pump  18 . The mechanism  20  comprises preferably the piercing element  17  and/or any other suitable connecting or actuation element. 
     In particular, in a first operation phase the piercing element  17  penetrates the seal  9  and, then, is inserted into the recess  16  and through the intermediate, end or weakened wall into the storage chamber  10 , and thus, connects the respective insert  6  to the gas supply. Before, simultaneously or afterwards, e.g., during the further movement, the mechanism  20  pushes the insert  6  through the other or outer opening  8  and through the respective seal  9  at least partially out of its cavity  7 . Preferably, the mechanism  20  acts directly on the respective insert  6  to cause its movement. Here, the piercing element  17  is preferably provided with a shoulder or abutment or sleeve  21  (shown schematically in  FIG. 6 ) abutting at the insert  6  to positively cause the desired movement of the insert  6  when moving the mechanism  20 /piercing element  17 . The final situation is shown in  FIG. 1  on the right side and in  FIG. 6  with protruding insert  6 . 
     It is noted that any other driving mechanism can be used to move the insert  6  to open one opening  8 /one seal  9 /respective outlet  15  or the insert  6  itself. In particular, it is possible to realize the preferred pushing of the insert  6  through the seal  9  independently of the connecting or piercing of the insert  6 . 
     In order to facilitate opening of the respective seal  9 , the insert  6  comprises preferably an opening means, in particular a tip portion  11   b , and/or is tapered at its outlet end. In particular, the insert  6  or its base  11  comprises an inclined or tapered portion  11   c —preferably at least or only on one flat side of the insert  6  or base  11 —so that the insert  6 /base  11  is inclined or tapered towards the outlet  15 , as shown schematically in  FIGS. 4 &amp; 6 . Thus, it is possible to form a tip or tip portion  11   b , which forms a front face with reduced or minimal surface. It is even possible to form a cutting edge at the outlet end and/or by the illustrated tip portion  11   b  or any other edge of the insert  6 . 
     Alternatively or additionally, it is possible to form or provide any other suitable cutting element as opening means at the insert  6 , in particular at its outlet end. 
     In particular, the stroke or outward movement of the insert  6  is adapted and preferably sufficiently long, such that the desired opening of the seal  6  is ensured, and in particular, that the broken, cut and/or ruptured parts of the opened seal  9  cannot hinder or cover or interfere with the outlet  15  of the insert  6 . In the present embodiment, the seal  9  substantially ruptures at one side of the opening  8  where the tip portion  11   b  of the insert  6  is located. The short remainder of the seal  9  mounted on this side of the opening  8  cannot interfere with the outlet  15  of the protruding insert  6  because it is preferably shorter than the outward stroke of the insert  6 . The longer part of the seal  9  connected to the other side of the opening  8  will be bent or pivoted away by the insert  6 . 
     In the present embodiment, the opening and/or cutting of the seal  9  takes place at one side or adjacent to one edge of the preferably rectangular opening  8  when the respective insert  6  is moved outward of its cavity  7  for activating and later dispensing. The opening means, tip portion  11   b , cutting element or the like is located at one side of the insert  6  and, in particular, adjacent to one side of its cavity  7  and opening  8  so that the mentioned opening of the respective seal  9  occurs as described when the insert  6  is moved outward. In other words, the location of the opening or cutting means may be and, in particular, is used to ensure or cause a desired opening pattern and/or location of the respective seal, in particular at one side and/or adjacent to one edge of the opening  8 . However, other opening locations can be chosen. For example, it is also possible to open the respective seal  9  in the center. Additionally or alternatively, the insert  6  may be adapted—in particular by provision of two or more opening or cutting means—to open or rupture or cut the respective seal  9  at multiple regions subsequently or simultaneously. 
     In the present embodiment, the insert  6  is preferably moveable radially and/or outwardly and/or away from the airpump  18  and/or in its longitudinal direction and/or in the main discharge direction and/or in the main extension of the mouthpiece  24 . However, other movements are also possible. In the present case, only a translational movement is produced. However, a rotational or pivotal movement can be produced additionally or alternatively or superposed. 
     Preferably, the storage device  4 , the carrier  5  and/or the cavities  7  comprise means for limiting the possible or maximum movement of the inserts  6 . Preferably, this means stops the insert(s)  6  by form-fit. In the present embodiment, the means comprise stops  22 , e.g., shoulders, protrusions or the like, which interact with a respective abutment, such as a shoulder  23 , of the respective insert  6  so that the insert  6  is limited in its movement out of the respective cavity  7  as shown schematically in  FIG. 6  where the shoulder  23  abuts the respective stop  22  and, thus, prohibits any further outward movement of the insert  6 . However, it is noted that any other technical solution having the same effect can also be used. 
     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) generates a respective flow in the storage chamber  10  to mix gas and powder and to force the dose through the duct  12 . 
     The powder will be discharged—in particular forced through the duct  12 —with a comparatively low gas pressure (preferably less than 300 kPa, in particular about 50 to 200 kPa). This low gas pressure, which is significantly lower than the gas pressures in the prior dispensing devices, enables a respectively low discharge velocity and, therefore, a slow spray  3  with slow propagation velocity. 
     Preferably the storage chamber  10  forms a mixing chamber for mixing the gas with the powder. The chamber  10  is preferably designed such that the gas can generate swirls or eddies for better mixing the powder with the gas. Preferably, the chamber  10  is substantially circular in cross section, in particular cylindrical. However, other shapes are also possible. 
     Further, the chamber  10  is formed with no sharp edges, corners or the like, but has a smooth contour so that the gas can sweep all chamber surfaces to prevent powder accumulating on said 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 located opposite to the outlet, i.e., duct  12  and/or nozzle  13 , with regard to the axial or outlet direction. 
     During the dispensing operation, the spray  3  is preferably directly or only generated by the respective insert  6  or its duct  12 /nozzle arrangement  13  and output into a mouthpiece  24  of the dispensing device  1  as shown in  FIG. 1  for inhalation by a patient or user (not shown). 
     After dispensing one dose or before or for dispensing the next dose, the piercing element  17  will be withdrawn from the connected insert  6 . Preferably, the respective insert  6  is also retracted or pushed back into its cavity  7 . 
     Then, the carrier  5  will be indexed one step further or to the next insert  6 , in particular rotated by means of an indexing or transport mechanism (not shown). This mechanism is preferably operated by actuating actuator  19  or any other actuator, by opening a cap or cover of the dispensing device  1  or the like, as already mentioned. 
     It is noted, that the present invention, in particular, the dispensing device  1  and/or the storage device  4 , can be used for dispensing one drug, a blend of drugs or at least two or three separate drugs. In the latter case, the separate drugs are stored in separate storage chambers  10  and, during the dispensing operation, the drugs are mixed with a gas either in a common mixing chamber or in their respective storage chambers  10 . Further, the separate drugs can be discharged through a common duct  12  or nozzle arrangement  13  or through separate ducts  12  or nozzles  13 . In the latter case, the separate drugs will be mixed after leaving the separate ducts  12 /nozzles  13  or in the mouthpiece  24  or in any other suitable (additional) mixing chamber. It is also possible to mix the separate drugs by impinging jets of the separate drugs. For dispensing the separate drugs, it is preferred to use a common gas supply or means for pressurizing gas such as air pump  18 . 
     Preferably, the spray  3  has a mean velocity (taken 20 cm from the outlet  15  or mouthpiece  24 ) of less than 2 m/s, in particular less than 1 m/s. Preferably, the mean duration of the spray  3  is at least 0.2 or 0.3 s, in particular about 0.5 to 25. 
     In the preferred embodiment according to  FIG. 1 , the cavities  7  are orientated in tangential or radial direction of the storage device  4  or carrier  5 . Consequently, the inserts  6  can be individually moved in tangential or a radial direction, in particular, outwardly, in order to open the respective outer seal  9  for dispensing the respective dose of the formulation  2  as indicated in  FIG. 1 . Accordingly, the mechanism  20  preferably operates in a radial direction for connecting the inserts  6  individually to a gas supply and for pushing the inserts  6  individually at least partially out of the respective cavity  7  and/or through the respective seal  9 . This radial movement allows a very compact design of the dispensing device  1 , in particular in axial direction. 
     Preferably, the mouthpiece  24  and the dispensing direction extends in a radial or tangential direction as shown in  FIG. 1 . 
     Preferably, the dispensing device  1  comprises a lever or handle (not shown) or the actuator  19  or any other driving or actuation means for preferably manual actuation in order to index the carrier  5  one step further, i.e., to the next insert  6 , and/or to operate the mechanism  20 , preferably to connect the respective insert  6  to the gas supply and/or to move/push the respective insert  6  and/or to open the respective seal  9  for dispensing the respective dose of the formulation  2 . 
     It is noted that the dispensing device  1  operates preferably only mechanically. 
     According to another embodiment (not shown), the inserts  6  may be formed as capsules or the like without any duct  12 , nozzle  13  or the like. Instead, each insert  6  is connected individually to a gas supply and to a common outlet arrangement, such as a duct  12 , nozzle  13  or the like for dispensing the respective dose of the formulation  2 . 
     According to another embodiment, a secondary packaging may be used for packing and protecting the storage device  4 /carrier  5 , in particular for storage purposes before inserting the storage device  4 /carrier  5  into the dispensing device  1 . Additionally, the whole device  1  including the storage device  4 /carrier  5  may be stored in a secondary water vapor proof packaging. 
     According to a further embodiment, the dispensing devise  1  may be breath activated, in particular wherein the formulation  2  is only released after the patient&#39;s or user&#39;s inhalation rate has reached a predetermined level, preferably by the use of a pressure sensitive means, such as a bursting element, membrane or valve, or any other mechanism. 
     According to another embodiment, the dispensing device  1  may also be a passive inhaler wherein a patient or user (not shown) produces an airflow through the respectively opened insert  6 , when breathing in so that this airflow entrains the formulation  2  and forms the desired spray  3  in the mouthpiece  24  for inhalation by the patient/user. 
     It is noted that the term “dispensing device” has to be understood preferably in a broad sense to include other discharge devices, dispensers or the like, preferably wherein the formulation  2  or any other fluid is sprayed or atomized only when needed, in particularly discontinuously. 
     In the following, a further preferred embodiment of the dispensing device  1  will be explained with reference to the further drawings. The following description will focus on relevant differences between the further embodiment and the previous embodiments. In particular, the previous explanations and descriptions apply accordingly and/or additionally, even if not repeated. 
       FIG. 7  shows the further embodiment of the dispensing device  1  in a perspective view. The dispensing device  1  comprises a cover  25  for covering the mouthpiece  24 . Preferably, the cover  25  is mounted to pivot for opening or uncovering the mouthpiece  24  as shown. Preferably, the mouthpiece  24  is snapped to a housing  26  of the dispensing device  1 . 
     The dispensing device  1  comprises the actuator  19  at one side of its housing  26 , preferably on the side opposite the mouthpiece  24  and/or opposite the main spray direction (preferably in radial direction) of the dispensing device  1 . The actuator  19  preferably forms a grip or handle. Therefore, the term “grip” will be used in the following. 
     The grip  19  is preferably moveable in radial direction for actuating the dispensing device  1  as explained later in more detail. In particular, the grip  19  can be pulled radially outwardly from the initial position shown in  FIG. 7  and pushed back into its initial position. These operations are, for convenience, named “pulling” and “pushing,” respectively, in the following. However, it is noted that these operational movements could also be realized by any other direction or type of movement, such as a non-translational movement. 
     First of all, the basic principle of the dispensing device  1  will be explained with reference to  FIGS. 8 to 10 .  FIGS. 8 to 10  show only very rudimentary schematic views (not to scale) of inner components of the dispensing device  1  for explaining the principle. In particular, the housing  26  and the grip  19  have been omitted. Further, the storage device  4  is shown only in a schematic manner, in particular, incompletely or partially only in  FIGS. 9 &amp; 10 . In particular, multiple details, such as seals  9 , outlets  15  or the like, have been omitted. The preferred construction of the storage device  4  will be explained later after explaining the basic functional principle of the present dispensing device  1 . 
     The dispensing device  1  is an active atomizer or inhaler. The means for pressurizing gas is preferably also constructed as air pump  18 . Here, the air pump  18  comprises a bellows  27  as pumping element. However, any other suitable pumping element could be used. 
     The dispensing device  1 /air pump  18  further comprises an energy or spring store, in particular a spring  28 , for actuating the pumping element, i.e., the bellows  27 . 
     The air pump  18  (bellows  27  and spring  28 ) is preferably radially moveable, in particular in a sliding manner or like a sled. Preferably, the air pump  18  forms a slider  29  or is supported thereof. In particular, the air pump  18  and slider  29  will be named “air assembly” in the following. 
     Preferably, the air assembly forms or includes the mechanism  20  already mentioned with respect to the previous embodiments. For this purpose, the air assembly preferably comprises a needle holder  30  holding the piercing element/needle  17 . The piercing element  17  may be pressed and/or glued or molded into the needle holder  30 . Preferably, the bellows  27  is pressed or clamped onto the needle holder  30 . 
     The needle holder  30  may be designed such that it can push the respective inserts  6  outwardly in case that the sleeve  21  or any other abutment fails. 
     The needle holder  4  preferably closes or completes the slider frame  31 . For example, the needle holder  30  may comprise holds for pins of the slider frame  31 , which pins may be heatriveted. 
     The needle holder  30  is connected to or formed by a slider frame  31 , which, in turn, holds the spring  28  and/or moveably guides a tension element  32  associated to the bellows  27  and/or spring  28 . 
     In the illustrated embodiment, the bellows  27  is arranged between the needle holder  30  and the tension element  32 . The spring  28  is arranged behind the bellows  27 , e.g., on the opposite side of the tension element  32 . 
     The tension element  32  holds the bellows  27  in order to secure the filling of the bellows  27  during pulling. Namely, the grip  19  preferably retracts the tension element  32  during pulling. 
     The air pump  18  or air assembly is preferably located in the center of the dispensing device  1  and/or within the storage device  4  and/or ring-like carrier  5  and/or is preferably radially moveable. 
       FIG. 8  shows the situation after the grip  19  (not shown) has been pulled out. The bellows  27  is extended and filled with air. The spring  28  is compressed or tensioned, i.e., the energy store has stored energy. The tension element  32  is retracted and locked in its position to hold the spring  28  in its compressed state. The air assembly/slider  29  is retracted so that the piercing element  27  is retracted from the storage device  4 , in particular so that the storage device  4  can be indexed or moved, in particular rotated. 
     When the grip  19  is pushed back, preferably a transportation operation and a connecting operation will be performed. In the first phase of the movement of the grip  19 , a transport mechanism  33  is actuated. In particular a cogwheel  34  of the transport mechanism  33  (shown in  FIG. 9 ) at least temporarily meshing with a preferably inner teeth  35  of the storage device  4  or carrier  5  is rotated to move or index the storage device  4  by one insert  6  or cavity  7  and/or to the next insert  6  or cavity  7 . However, it is noted that this transportation operation could also be performed partly or completely during pulling. 
     Preferably after termination of the transportation operation, i.e., during a second phase of pushing, the connecting operation is performed. The air assembly/slider  29  is moved forward and/or radially so that the piercing element  17  connects to the next/aligned insert  6 /cavity  7 . In particular, the piercing element  17  pierces into the insert  6  to connect to its storage chamber  10 . Before, simultaneously and/or subsequently, the insert  6  is moved radially and/or outward and/or pushed through the outer seal  9 . As a result, the insert  6 /duct  12 /outlet  15  is opened. This situation is shown in  FIG. 9 , wherein the connected and opened insert  6  is protruding radially outwardly from the storage device  4  and/or its cavity  7 . 
     The spring  28  is still biased or compressed. This situation is also named “activated state.” The dispensing device  1  is ready for dispensing the dose of formulation  2  from the opened/protruding inserts  6  shown in  FIG. 9 . 
     To initiate delivery (discharge) of the formulation  2  and to generate the spray  3 , a release button  36  (shown in  FIG. 7 ) or any other suitable element is actuated, in particular depressed. Thus, the tension element  32  or its associated locking means is unlocked (preferably by depressing/compressing the elastic snap  32   a ), and the spring  28  is released and compresses the bellows  27 . The bellows  27  compresses the air contained therein. Thus, the air is pressed through piercing element  17  into the connected insert  6 . The resulting air stream is forced through the connected insert  6 , entrains the powder/formulation  2  of the insert  6  and ejecting it as spray  3  (not shown). 
       FIG. 10  shows the final state after discharge. The spring  28  has expanded and the bellows  27  compressed. The tension element  32  has been moved forward to the needle holder  30 /piercing element  17 . The piercing element  17  is still connected to the emptied insert  6 , and the emptied insert  6  is still protruding outward. In this state, the dispensing device  1  can be closed and transported. Therefore, this state is also named “transportation state.” 
     For the next use, the grip  19  is pulled. In a first phase of the movement, the slider  29 /air assembly is retracted together with the piercing element  17  so that the piercing element  17  is retracted from the storage device  4 , i.e., out of the cavity  7  of the last insert  6 . In a second phase of movement, which can also happen simultaneously, but is preferably performed after the slider  29  has stopped, the tension element  32  is retracted within the slider  29 /slider frame  31  so that the bellows  27  is extended and the spring  28  is compressed or biased until the tension element  32  is locked in its retracted position as shown in  FIG. 8 . During the extension of the bellows  27 , air is sucked into the bellows  27 , preferably through piercing element  17  and/or optionally through a suitable inlet valve (not shown). 
     It is noted that the release button  36  is preferably lifted only during the last phase of pushing the grip  19 . Further, the lifted or activated or primed release button  36  preferably blocks pulling of the grip  19  until the release button  36  has been actuated or depressed, i.e., until the dispensing device  1  has been triggered. In particular, the release button  36  is tilted during actuation or depressing. 
     In the following, further details, aspects, features and advantages of the present dispensing device  1  and/or of its components will be explained. 
     Preferably, the storage device  4  comprises multiple receptacles  37  respectively containing only or at least one insert  6 , as schematically shown in  FIGS. 8 to 10 . In particular, the receptacles  37  are produced as separate parts that are placed or mounted on the carrier  5 . 
     The receptacles  37  may be made of the same material as the storage device  4 /carrier  5 , in particular of plastic. Preferably, the receptacles  37  are rigid and form a guide for the inserts  6 . 
     Each of the receptacles  37  comprises one or more cavities  7  for receiving the respective insert(s)  6 . 
     Preferably, the receptacles  37  are provided with the inserts  6  already filled with the respective dose of formulation  2 , and then, mounted on the comment carrier  5 . 
     The receptacles  37  are preferably sealed separately, i.e., independently from each other and/or with separate seals  9 . The receptacles  37  may be sealed before or after placement on the carrier  5 . The receptacles  37  are preferably sealed on opposite sides and/or on longitudinal end faces. 
       FIG. 11  shows in a schematic perspective view one receptacle  37  before placement on the carrier  5 . Preferably, the receptacle  37  has an essentially cuboid and/or longitudinal form. 
     The carrier  5  preferably supports the receptacles  37  fixedly and/or in a form-fit manner. Preferably, the receptacles  37  are snapped on to or into the carrier  5 . 
     In the present embodiment, the receptacles  37  comprise a protrusion  38  for mounting the respective receptacle  37  to carrier  5 . The carrier  5  comprises a series of corresponding recesses  39 , such as slits or grooves, as shown in  FIGS. 9 &amp; 10 . In the embodiment shown in  FIG. 11 , there are bores for receiving the protrusions  38 . In particular, the receptacles  37  can be snapped, clipped, clamped or pressed with their protrusions  38  into the recesses  39  of the carrier  5 . For this purpose, the protrusions  38  may comprise a preferably annular portion  38   a  with increased diameter or the like.  FIG. 12  shows in a schematic perspective view a preferred embodiment of the carrier  5  with the bores being provided as recesses  39 . Preferably, the recesses and/or protrusions  38  are arranged adjacent to the inner surfaces of the storage device  4 , to the inner openings  8  and/or to the side at which piercing or pushing of the respective inserts  6  occurs. However, other mechanical solutions or designs are possible to connect the receptacles  37  with the carrier  5 . 
     Alternatively or in addition to the recesses or bores  39 , the carrier  5  may comprise means for fixing and/or aligning the receptacles  37  on the carrier  5 . In the illustrated embodiment, the carrier  5  preferably comprises an inner ring wall  40  and/or holding elements  41 . 
     The inner ring wall  40  may form an abutment or stop for the inserts  6  which prevent the inserts  6  from being pulled out of their cavities  7  when retracting the piercing element  17 . 
     The holding elements  41  are preferably located at the periphery of the carrier  5  and protrude preferably upwardly so that each receptacle  37  can be placed between two adjacent holding elements  41 . In particular, the holding elements  41  align the receptacles  37  on the carrier  5  correctly and/or radially. 
     Preferably, the receptacles  37  can be snapped or clamped between adjacent holding elements  41 . For this purpose, the receptacles  37  may comprise noses  42  or other suitable engaging means on its respective sides which can be engaged or hooked by the preferably flexible and/or arm-like holding elements  41 . Thus, it is possible to hold or fix the receptacles  37  at its outer periphery and/or such that any tilting can be avoided, even when the piercing element  17  is retracted. 
     It is noted that the carrier  5  preferably comprises a “dummy” receptacle  43  without any insert  6  for receiving the piercing element  17  in the initial transportation state (delivery state) of the dispensing device  1 , i.e., before first use of the dispensing device  1 , wherein the assembly is in the position shown in  FIG. 10 , but the piercing element  17  extends into the dummy receptacle  43 . 
       FIG. 13  shows in a partial, enlarged view of the carrier  5  the preferably hollow dummy receptacle  43 . In particular, the dummy receptacle  43  is axially open at one side (slit  43   a ) and/or is radially open at its inner side so that the piercing element  17  can be axially inserted when mounting the dispensing device  1 . 
     Further,  FIG. 13  shows that the holding elements  41  are preferably provided with undercuts or transversely extending portions at their free ends or other suitable means to surely hold the receptacles  37  between the holding elements  41  by engaging the noses  42 . 
       FIG. 14  shows a partial, enlarged view of the carrier  5  from the other side. 
     The dispensing device  1  comprises preferably a lifespan block (LSB). After using or operating the dispensing device  1  for the predetermined number of uses (number of doses or inserts  6 ), in the present embodiment e.g.,  30  applications, the dispensing device  1  is locked up completely in order to avoid any further inadvertent applications. Preferably, the dispensing device  1  has multiple independently working LSB locks. In particular, the locks are unlockable and/or lock by form-fit. 
     The first LSB lock may be formed by an abutment, such as a rib  44  as shown in  FIG. 14  or the like, on the storage device  4  or its carrier  5 . The abutment limits the rotation of the storage device  4 /carrier  5  in that it abuts at a respective stop provided by the housing  26  or any other suitable, in particular, rigid or stationary part of the dispensing device  1  when the last insert  6 /cavity  7  has been aligned with respect to the air assembly or piercing element  17 . 
     A second LSB lock may be formed by a snap nose  45  formed on the storage device  4 , in particular the carrier  5  as shown in  FIG. 13 , for locking the release button  36  in its actuated or depressed position after the last use of the dispensing device  1 . Thus, any further triggering or any further pump operation would be prevented. 
     A third LSB lock may be formed by a snap hook  46  also provided at the storage device  4 , in particular the carrier  5 , for locking the grip  19  in the inner or pushed position (as shown in  FIG. 7 ) when the storage device  4 /carrier  5  has reached its end position and the storage device  4 /carrier  5  has reached its last position/receptacle  37 . In particular, the grip  19  may hook with one holding arm or two holding arms  57  (shown in  FIG. 16 ) to the snap hook  46  in the locked state. 
     Preferably, the storage device  4 /carrier  5 /receptacles  37  interact with an air assembly/slider  29  such that a correct alignment of the piercing element  17  and the respective receptacle  37  or insert  6  is ensured before the piercing element  17  pierces or opens the respective receptacle  37 , cavity  7  and/or insert  6 . For this purpose, the air assembly or slider  29  preferably comprises an engagement portion, in particular a fork portion  47  ( FIG. 15 ), which interacts with the storage device  4 , carrier  5  and/or the respective receptacle  37  to achieve the desired (fine) alignment. 
     In the present embodiment, the engagement portion or fork portion  47  protrudes from the air assembly, in particular from the needle holder  30 , which is shown in detail in  FIG. 15 . The engagement portion or fork portion  47  preferably interacts with alignment means or guiding portions associated to each insert  6 . In the present embodiment, these alignment means or guiding portions are preferably formed by the protrusions  38 , which protrude through the recesses  39  and extend outwardly or axially from the carrier  5 . Thus, a direct and optimized (fine) alignment can be positively achieved between the piercing element  17  and the respective insert  6  with minimal tolerances. 
     Preferably, the inserts  6  are restricted in their backward movement as already mentioned so that the piercing element  17  can be retracted and uncoupled from the respective insert in a definitive manner when the air assembly/slider  29  is retracted into the position shown in  FIG. 8 . This restriction or limitation is preferably achieved by a respective stop or abutment at the storage device  4  or carrier  5 . In particular, this stop or abutment is formed by the inner ring wall  40  or any other suitable means. 
     The dispensing device  1  preferably comprises a counter for counting or showing the used or unused doses or operations. Preferably, the counter device is formed by a numbering  48  on the storage device  4 , in particular on the carrier  5  as shown in  FIG. 14 . The numbering  48  is visible through a respective window or transparent portion (not shown) of the housing  26 . 
     The dispensing device  1  preferably comprises a means for preventing a backstroke of the air assembly, in particular of the piercing element  17 , when discharge of a dose of formulation  2  is triggered (by actuating release button  36 ) and the spring  28  moves forward and the gas or air is forced through the respective insert  6 . Preferably, this means is realized by respective locking of the grip  19  against pulling. In particular, the grip  19  has to be decoupled before it can be pulled. In the present embodiment, the decoupling can be achieved by depressing a portion  49  of the grip  19 , in particular by pressing opposite portions  49  of the grip  19  together so that a respective undercut or snap engagement between the grip  19  and the housing  26  can be unlocked. In particular, the grip  19  consists of two grip parts or halves  50  as shown in  FIG. 16 . Preferably, each half  50  comprises a flexible or depressible portion  49  with an associated snap portion  51 . The snap portion can engage into a recess or undercut  51   a  formed in the housing  26  as schematically shown in  FIG. 16  to lock the grip  19  in the pushed position ( FIG. 16  shows the grip  19  in the pulled position). 
     The dispensing device  1  comprises preferably a means for moving or pressing the used inserts  6  back into their respective cavities  7  or receptacles  37 . This means preferably comprises at least one preferably stationary and/or rigid guiding element  52 , here multiple rib-like guiding elements  52  are arranged inside the housing  26  adjacent to the outer periphery of the storage device  4  and after the mouthpiece  24 , in particular on or in one half  53  of the housing  26  as shown in  FIG. 17 . Due to the relative movement of the storage device  4  and the housing  26  or guiding elements  52 , inclined surfaces  52   a  of the guiding elements  52  press or push the used insert  6  back into the storage device  4  or its respective cavity  7  or receptacle  37 , preferably in multiple steps. Alternatively or additionally the inclined portions  11   c  of the inserts  6  may be used to move, press or urge the used inserts  6  back into their cavities  7 , in particular in cooperation with a preferably stationary guiding element  52  or the like. 
     In the present embodiment, a locking means is provided for locking the tension element  32  in the retracted position. Here, the locking means comprises at least one snap hook or arm  32   a , preferably two or more snap arms  32   a  engaging into respective undercuts, recesses or snap openings  32   b  preferably formed by or in a back shield  32   c  of the slider  29  or slider frame  31  or vice versa. However, other constructional solutions are possible. 
     The dispensing device  1  is preferably an active powder inhaler, i.e., the powder is discharged by pressurized gas, in particular air. Nevertheless, the dispensing operation may be triggered by the inhalation or breathing in of a patient (not shown). In particular, the dispensing device  1  comprises detection means for detecting inhalation or breathing in and/or trigger means for triggering dispensing of the respective dose. 
     Preferably, the detection means comprises a sensor  55  for detecting at least one of a pressure, a pressure drop, a velocity, an increase of velocity or any associated value thereof regarding the air flowing through the dispensing device, in particular, the mouthpiece  24 , when a patient breathes in. The respective detection signal indicating breathing in of a patient may be used by the trigger means in order to trigger dispensing of the respective dose by means of pressurized gas. In particular, the trigger means comprises a controller  54  and/or a valve  56  associated with the means for pressurizing gas, in particular the air pump  18 , a gas supply line, the piercing element  17  or the like controls or triggers the flow of pressurized gas to and through the respective storage chamber  10  or the like for dispensing the respective dose of formulation  2 . 
     Preferably, the trigger means operates electrically, electronically, pneumatically or mechanically. For example, the detection means and trigger means may be formed only by an appropriate valve  65  that opens the supply of pressurized gas through the respective receptacle  37 , insert  6  and/or storage chamber  10  when the pressure in the mouthpiece  24  drops due to breathing in of a patient. Then, the valve  56  preferably stays open until the flow of pressurized gas stops or the gas pressure reaches or drops bellow an appropriate pressure limit. Such a functionality may be realized without using electric or electronic components. 
     There are multiple other mechanisms possible. According to another embodiment, a sealed outer case can have a flexible diaphragm, e.g., made of rubber, mounted within its wall with one surface facing the inside and the other exposed to atmosphere. A linkage with mechanical advantage (amplification) connects the diaphragm to the tension element  32  ( FIGS. 8 &amp; 9 ) or to the valve  56  or any other suitable means to control gas supply. When the user or patient inhales via the mouthpiece  24  the sealed case ensures a pressure reduction due to which the diaphragm bends into the case activating or acting on the mechanical link, and thus, triggers dispensing, in particular, by releasing tension element  32 , opening valve  56  or the like. 
     According to another embodiment, a flap can be seally positioned within the mouthpiece  24  and connected to the tension element  32 , the valve  56  or the like via a linkage with mechanical advantage or amplification. When the user or patient inhales, the air flow/pressure difference opens or actuates the flap activating or operating the link, and thus, triggers dispensing, in particular, by releasing tension element  32 , opening valve  56  or the like. 
     According to another embodiment, an electronic system can be used. A pressure sensitive actuator can be connected to tension element  32  so that tension element  32  can be released when detecting inhalation or breathing in of a user or patient. 
     Preferably, the automatic triggering or dispensing is only possible when the dispensing device  1  has been activated and/or dispensing has been allowed, in particular by actuating the release button  36  or any other actuator, before the trigger means may eventually trigger the dispensing when breathing in is detected. 
     Preferably, the grip  19  and the tension element  32  interact directly or indirectly such that the tension element  32  can be moved by pulling the grip  19  to compress the spring  28 , but can move back into the position with decompressed spring  28  without movement of grip  19  when triggering dispensing. For this purpose, the tension element  32  engages preferably into a slit portion  58 , in particular formed by grip  19 . 
     Preferably, the insert  6 , the cavities  7  and/or the receptacles  37  are annually arranged. However, any other arrangement, in particular a linear arrangement or the like, is also possible. 
     In particular, the dispensing device  1  is a preferably oral and/or active inhaler, a hand-held device and/or preferably only manually operated. Most preferably, the dispensing device  1  is a dry powder inhaler. 
     Individual features and aspects of the individual embodiments may also be combined with one an other as desired or used in other constructions of atomizers, inhalers, dispensers or the like. 
     Some preferred ingredients and/or compositions of the preferably medicinal formulation  2  are listed below. As already mentioned, they are in particular powders or liquids in the broadest sense. Particularly preferably the formulation  2  contains the following: 
     The compounds listed below may be used in the device according to the invention on their own or in combination. In the compounds mentioned below, W is a pharmacologically active substance and is selected (for example) from among the betamimetics, anticholinergics, corticosteroids, PDE4-inhibitors, LTD4-antagonists, EGFR-inhibitors, dopamine agonists, H1-antihistamines, PAF-antagonists and PI3-kinase inhibitors. Moreover, double or triple combinations of W may be combined and used in the device according to the invention. Combinations of W might be, for example:
         W denotes a betamimetic, combined with an anticholinergic, corticosteroid, PDE4-inhibitor, EGFR-inhibitor or LTD4-antagonist,   W denotes an anticholinergic, combined with a betamimetic, corticosteroid, PDE4-inhibitor, EGFR-inhibitor or LTD4-antagonist,   W denotes a corticosteroid, combined with a PDE4-inhibitor, EGFR-inhibitor or LTD4-antagonist   W denotes a PDE4-inhibitor, combined with an EGFR-inhibitor or LTD4-antagonist   W denotes an EGFR-inhibitor, combined with an LTD4-antagonist.       

     The compounds used as betamimetics are preferably compounds selected from among albuterol, arformoterol, bambuterol, bitolterol, broxaterol, carbuterol, clenbuterol, fenoterol, formoterol, hexoprenaline, ibuterol, isoetharine, isoprenaline, levosalbutamol, mabuterol, meluadrine, metaproterenol, orciprenaline, pirbuterol, procaterol, reproterol, rimiterol, ritodrine, salmefamol, salmeterol, soterenol, sulphonterol, terbutaline, tiaramide, tolubuterol, zinterol, 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]sulphonyl}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-3-one   6-hydroxy-8-{1-hydroxy-2-[2-(ethyl 4-phenoxy-acetate)-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]-formamide   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)-benzylsulphonamide   3-(3-{7-[2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino]-heptyloxy}-propyl)-benzylsulphonamide   4-(2-{6-[4-(3-cyclopentanesulphonyl-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 the racemates, enantiomers, diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates or hydrates thereof. According to the invention the acid addition salts of the betamimetics are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.   

     The anticholinergics used are preferably compounds selected from among the tiotropium salts, preferably the bromide salt, oxitropium salts, preferably the bromide salt, flutropium salts, preferably the bromide salt, ipratropium salts, preferably the bromide salt, glycopyrronium salts, preferably the bromide salt, trospium salts, preferably the chloride salt, tolterodine. In the above-mentioned salts the cations are the pharmacologically active constituents. As anions the above-mentioned salts may preferably contain the chloride, bromide, iodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate or p-toluenesulphonate, while chloride, bromide, iodide, sulphate, methanesulphonate or p-toluenesulphonate are preferred as counter-ions. Of all the salts the chlorides, bromides, iodides and methanesulphonates are particularly preferred. 
     Other preferred anticholinergics are selected from among the salts of formula 
                         
wherein X −  denotes an anion with a single negative charge, preferably an anion selected from among the fluoride, chloride, bromide, iodide, sulphate, phosphate, methanesulphonate, nitrate, maleate, acetate, citrate, fumarate, tartrate, oxalate, succinate, benzoate and p-toluenesulphonate, preferably an anion with a single negative charge, particularly preferably an anion selected from among the fluoride, chloride, bromide, methanesulphonate and p-toluenesulphonate, particularly preferably bromide, optionally in the form of the racemates, enantiomers or hydrates thereof. Of particular importance are those pharmaceutical combinations which contain the enantiomers of formula AC-1-en
 
                         
wherein X −  may have the above-mentioned meanings. Other preferred anticholinergics are selected from the salts of formula AC-2
 
                         
wherein R denotes either methyl or ethyl and wherein X −  may have the above-mentioned meanings. In an alternativen embodiment the compound of formula AC-2 may also be present in the form of the free base AC-2-base.
 
     
       
         
         
             
             
         
       
     
     Other specified compounds are:
     tropenol 2,2-diphenylpropionate methobromide,   scopine 2,2-diphenylpropionate methobromide,   scopine 2-fluoro-2,2-diphenylacetate methobromide,   tropenol 2-fluoro-2,2-diphenylacetate methobromide;   tropenol 3,3′,4,4′-tetrafluorobenzilate methobromide,   scopine 3,3′,4,4′-tetrafluorobenzilate methobromide,   tropenol 4,4′-difluorobenzilate methobromide,   scopine 4,4′-difluorobenzilate methobromide,   tropenol 3,3′-difluorobenzilate methobromide,   scopine 3,3′-difluorobenzilate methobromide;   tropenol 9-hydroxy-fluorene-9-carboxylate methobromide;   tropenol 9-fluoro-fluorene-9-carboxylate methobromide;   scopine 9-hydroxy-fluorene-9-carboxylate methobromide;   scopine 9-fluoro-fluorene-9-carboxylate methobromide;   tropenol 9-methyl-fluorene-9-carboxylate methobromide;   scopine 9-methyl-fluorene-9-carboxylate methobromide;   cyclopropyltropine benzilate methobromide;   cyclopropyltropine 2,2-diphenylpropionate methobromide;   cyclopropyltropine 9-hydroxy-xanthene-9-carboxylate methobromide;   cyclopropyltropine 9-methyl-fluorene-9-carboxylate methobromide;   cyclopropyltropine 9-methyl-xanthene-9-carboxylate methobromide;   cyclopropyltropine 9-hydroxy-fluorene-9-carboxylate methobromide;   cyclopropyltropine methyl 4,4′-difluorobenzilate methobromide.   tropenol 9-hydroxy-xanthene-9-carboxylate methobromide;   scopine 9-hydroxy-xanthene-9-carboxylate methobromide;   tropenol 9-methyl-xanthene-9-carboxylate-methobromide;   scopine 9-methyl-xanthene-9-carboxylate-methobromide;   tropenol 9-ethyl-xanthene-9-carboxylate methobromide;   tropenol 9-difluoromethyl-xanthene-9-carboxylate methobromide;   scopine 9-hydroxymethyl-xanthene-9-carboxylate methobromide,   

     The above-mentioned compounds may also be used as salts within the scope of the present invention, wherein instead of the methobromide the salts metho-X are used, wherein X may have the meanings given hereinbefore for X − . 
     As corticosteroids it is preferable to use compounds selected from among beclomethasone, betamethasone, budesonide, butixocort, ciclesonide, deflazacort, dexamethasone, etiprednol, flunisolide, fluticasone, loteprednol, mometasone, prednisolone, prednisone, rofleponide, triamcinolone, RPR-106541, NS-126, ST-26 and
     (S)-fluoromethyl 6,9-difluoro-17-[(2-furanylcarbonyl)oxy]-11-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17-carbothionate   (S)-(2-oxo-tetrahydro-furan-3 S-yl)6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-propionyloxy-androsta-1,4-diene-17-carbothionate,   cyanomethyl 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-(2,2,3,3-tertamethylcyclopropylcarbonyl)oxy-androsta-1,4-diene-17β-carboxylate
 
optionally in the form of the racemates, enantiomers or diastereomers thereof and optionally in the form of the salts and derivatives thereof, the solvates and/or hydrates thereof. Any reference to steroids includes a reference to any salts or derivatives, hydrates or solvates thereof which may exist. Examples of possible salts and derivatives of the steroids may be: alkali metal salts, such as for example sodium or potassium salts, sulphobenzoates, phosphates, isonicotinates, acetates, dichloroacetates, propionates, dihydrogen phosphates, palmitates, pivalates or furoates.
   

     PDE4-inhibitors which may be used are preferably compounds selected from among enprofyllin, theophyllin, roflumilast, ariflo (cilomilast), tofimilast, pumafentrin, lirimilast, arofyllin, atizoram, D-4418, Bay-198004, BY343, CP-325.366, D-4396 (Sch-351591), AWD-12-281 (GW-842470), NCS-613, CDP-840, D-4418, PD-168787, T-440, T-2585, V-11294A, CI-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-[(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-5-methyl-isothioureido]benzyl)-2-pyrrolidone   cis[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane-1-carboxylic acid]   2-carbomethoxy-4-cyano-4-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)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   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 the racemates, enantiomers or diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts thereof, the solvates and/or hydrates thereof. According to the invention the acid addition salts of the betamimetics are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.
   

     The LTD4-antagonists used are preferably compounds selected from among 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)thio)methylcyclopropane-acetic acid,   1-(((1(R)-3(3-(2-(2,3-dichlorothieno[3,2-b]pyridin-5-yl)-(E)-ethenyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetic acid   [2-[[2-(4-tert-butyl-2-thiazolyl)-5-benzofuranyl]oxymethyl]phenyl]acetic acid
 
optionally in the form of the racemates, enantiomers or diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates and/or hydrates thereof. According to the invention the acid addition salts of the betamimetics are preferably selected from among the hydrochloride, hydrobromide, hydroiodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate. By salts or derivatives which the LTD4-antagonists may optionally be capable of forming are meant, for example: alkali metal salts, such as for example sodium or potassium salts, alkaline earth metal salts, sulphobenzoates, phosphates, isonicotinates, acetates, propionates, dihydrogen phosphates, palmitates, pivalates or furoates.
   

     EGFR-inhibitors which may be used are preferably compounds selected from among 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-to-(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-to-(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-methanesulphonyl-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-to-(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-cyclohexan-1-yloxy)-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-methanesulphonylamino-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-methyl-piperidin-4-yloxy)-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-{-[(morpholin-4-yl)carbonyl]-piperidin-4-yl-oxy}-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-{1-[(methoxymethyl)carbonyl]-piperidin-4-yl-oxy}-7-methoxy-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)sulphonylamino]-cyclohexan-1-yloxy}-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-{trans-4-[(morpholin-4-yl)carbonylamino]-cyclohexan-1-yloxy}-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-{trans-4-[(morpholin-4-yl)sulphonylamino]-cyclohexan-1-yloxy}-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-(2-acetylamino-ethoxy)-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-(tetrahydropyran-4-yloxy)-7-(2-methanesulphonylamino-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}-cyclohexan-1-yloxy)-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)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-(cis-4-{N-[(morpholin-4-yl)sulphonyl]-N-methyl-amino}-cyclohexan-1-yloxy)-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-(trans-4-ethanesulphonylamino-cyclohexan-1-yloxy)-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-piperidin-4-yloxy)-7-ethoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-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-cyclohexan-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}-cyclohexan-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}-cyclohexan-1-yloxy)-7-methoxy-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-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-methanesulphonyl-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-cyclohexan-1-yloxy)-7-methoxy-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-{cis-4-[N-(2-methoxy-acetyl)-N-methyl-amino]-cyclohexan-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-methanesulphonyl-N-methyl-amino)-cyclohexan-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-methanesulphonyl-N-methyl-amino)-cyclohexan-1-yloxy]-7-methoxy-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)-ethoxy]-7-[(S)-(tetrahydrofuran-2-yl)methoxy]-quinazoline   4-[(3-chloro-4-fluoro-phenyl)amino]-6-(1-methanesulphonyl-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 the racemates, enantiomers, diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates or hydrates thereof. According to the invention the acid addition salts of the betamimetics are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate.
   

     The dopamine agonists used are preferably compounds selected from among bromocriptin, cabergoline, alpha-dihydroergocryptine, lisuride, pergolide, pramipexol, roxindol, ropinirol, talipexol, tergurid and viozan, optionally in the form of the racemates, enantiomers, diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates or hydrates thereof. According to the invention the acid addition salts of the betamimetics are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydrooxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate. 
     H1-Antihistamines which may be used are preferably compounds selected from among epinastine, cetirizine, azelastine, fexofenadine, levocabastine, loratadine, mizolastine, ketotifen, emedastine, dimetindene, clemastine, bamipine, cexchlorpheniramine, pheniramine, doxylamine, chlorophenoxamine, dimenhydrinate, diphenhydramine, promethazine, ebastine, desloratidine and meclozine, optionally in the form of the racemates, enantiomers, diastereomers thereof and optionally in the form of the pharmacologically acceptable acid addition salts, solvates or hydrates thereof. According to the invention the acid addition salts of the betamimetics are preferably selected from among the hydrochloride, hydrobromide, hydriodide, hydrosulphate, hydrophosphate, hydromethanesulphonate, hydronitrate, hydromaleate, hydroacetate, hydrocitrate, hydrofumarate, hydrotartrate, hydroxalate, hydrosuccinate, hydrobenzoate and hydro-p-toluenesulphonate. 
     It is also possible to use inhalable macromolecules, as disclosed in European Patent Application EP 1 003 478 A1 or Canadian Patent Application CA 2297174 A1. 
     In addition, the compounds may come from the groups of ergot alkaloid derivatives, the triptans, the CGRP-inhibitors, the phosphodiesterase-V inhibitors, optionally in the form of the racemates, enantiomers or diastereomers thereof, optionally in the form of the pharmacologically acceptable acid addition salts, the solvates and/or hydrates thereof. 
     Examples of ergot alkaloid derivatives are dihydroergotamine and ergotamine.