DE10300982A1 - powder inhaler - Google Patents

Abstract

The invention relates to powder inhalers in which at least a part of the inner surfaces that can come into contact with the powder aerosol is microstructured. This is preferably a powder inhaler (Bernoulli inhaler) working according to the Bernoulli principle.

Description

The invention relates to powder inhalers, in which at least part of the inner surfaces are coated with the powder aerosol in touch can come, is microstructured. It is preferably a Powder inhaler (Bernoulli inhaler) working according to the Bernoulli principle.

State of the art

The literature knows several powder inhalers working according to different principles. Since the Bernoulli inhalers according to the invention are preferred, these are first discussed. The Bernoulli inhalers have in common that the one to be deployed Active ingredient is stored in a cylindrical capsule and this Capsule is inserted into a capsule chamber of the inhaler. The Capsule chamber is usually also cylindrical, being a little longer and is slightly wider than the capsule, so the capsule in it can vibrate both vertically and horizontally, but in doing so remains aligned substantially parallel to the chamber axis. The Capsule chamber has an air inlet in the area of one of the two ends and an air outlet opening in the area of the other end. The air outlet (air duct) leads to a mouthpiece. To dispense the active capsule content, first the Capsule on usual two places on the long side jacket open. The openings are usually found nearby of the two long sides Ends of the capsule. If there is an airflow in the capsule chamber from Air inlet generated to the air outlet, this leads along the longitudinal axis the capsule and does two things: First, the capsule through the air flow mainly moved along its longitudinal axis. It can also vibrate in a small area. On the other hand creates the two capsule openings flowing along Air in front of the capsule openings across from the inside of the capsule, so that the inside of the capsule Powder is entrained by the air flow and atomized in the process.

The usual for such inhalers Capsules used consist of two cup-like parts are telescopically insertable. The outer form of such an assembled Capsule is that of a closed cylinder with hemispherical ends. The cylinder has a longitudinal axis and a transverse axis. The longitudinal axis is the axis that is parallel to the generatrix of the cylinder jacket lies. The longitudinal axis is longer than the transverse axis, so the longitudinal cut the capsule is oval, the cross-section is circular having.

The capsules for powder inhalants usually consist of hard gelatin, but they can also consist of a plastic material. In this context, the EP 1100474 directed.

The DE 3345722 discloses an inhaler working according to the Bernoulli principle, consisting of two housing elements with a single capsule chamber that can be moved in the radial direction. The inner surface of the hollow cylindrical capsule chamber is smooth.

WO 91/02558 discloses another Bernoulli inhaler, however, instead of a single capsule chamber, several capsule chambers similar to a revolver magazine are summarized. The open sides of this Magazines are through walls limited, with only at one point in these walls the Air inlet or air outlet is located. This magazine is rotatable stored so that a capsule chamber is only in a certain position with the air inlet, the air outlet and the ones for opening the Capsule necessary cutting elements is connected.

Also the EP 0911047 discloses a Bernoulli inhaler. This consists of a) an upwardly open, cup-shaped lower part, b) a plate which covers the opening of the lower part and is formed perpendicular to the one capsule chamber of the type described above, a button which is movable against a spring being provided on the capsule chamber , which has two ground needles for opening the capsule, c) an upper part with a mouth tube, which - being able to conduct a powder aerosol - is connected to the capsule chamber and d) a lid. The elements a), b) c) and d) are connected to one another by a common hinge element, so that they can be moved against one another in a foldable manner.

In addition, this patent application describes one Capsule holder, the capsule holder being designed as a hole in the plate b) can be and has ribs on the edge. The capsule is in this Capsule holder clamped for the purpose of storage.

The FR-A-2 146 202 describes a powder inhaler with a flat cylindrical chamber for receiving a capsule. The capsule, which is open at the ends, rotates around its transverse axis during the inhalation process, driven by tangentially flowing air.

In the US-A-4 069 819 describes a powder inhaler in which the capsule is pierced through the base of the capsule chamber and is set in motion during inhalation by the air entering tangentially near the base. Replica and testing of the inhaler according to the US-A-4 069 819 showed that the active ingredient application is uneven and very incomplete (below 40%), whereas for the Bernoulli inhalers described above, emptying of over 90% was regularly achieved when using the same capsules and powders.

Other powder inhalers that do not work according to the Bernoulli principle include those in the DE 3348370 and in the DE 3336486 disclosed in halators, which contain a disc-shaped blister pack, which has a plurality of blisters arranged in a circle. The individual blisters each contain a dose of a medicinal powder intended for inhalation. The blister pack contains the doses of the drug powder to be applied without being encapsulated. The blister pack for these inhalers is located in a chamber (storage chamber) and each of the blisters can be pierced on two opposite sides perpendicular to the disc plane. An air duct connects the opened blister to the mouthpiece. The inhaler of the DE 3336486 described in more detail. This has a housing in which there is a chamber (storage chamber) which has an air inlet and in which there is a disk-shaped, round blister with packaged medicament pockets. The blister is loosely connected to a round, rotatable disc. Holes are circumferentially formed on the disk, which have axial contact with the medication pockets, ie the pockets and holes lie above or below one another. The chamber has an air outlet. The inhaler also has a plunger, which is arranged such that it can open a medication pouch in each case so that the medication is released into the chamber and can be inhaled through a mouthpiece. Reference is made to the drawings of the patent application or the US patent.

The DE 4106379 describes an inhalation device into which a blister or the like for a powdered medicament can be inserted. The blister consists of two removable webs of material that define at least one container in which the medication is located. The device is provided with a device which pulls the two material webs apart from one another at an opening station in order to open a container. The user can inhale the powdered medicament from the opened container via an outlet part, for example a mouthpiece, which is connected to the opened container. One of the material webs can also be a carrier web with several pockets and the other material web can be a cover web. Each pocket and the adjacent area of the cover sheet then form a container. A drive device can be provided at the opening station, which pulls the carrier web and the cover web apart from one another. This drive device consists, for example, of two drive wheels (eg toothed wheels) which hold the cover sheet in drive engagement between them. In this case too, each individual blister defines a kind of storage chamber in the inhaler, which is connected to the mouthpiece via an air duct.

The US 4524769 discloses a powder inhaler having a nozzle (mouthpiece) for dispensing the aerosol, an air channel and a storage chamber for the active ingredient. A membrane can be moved back and forth between the air duct and the storage chamber. This membrane has a large number of devices for receiving a metered amount of active substance. The membrane is preferably a conveying membrane which preferably has holes or perforated depressions as a device for transporting active substance from the storage chamber into the air duct. At least one of the devices is always pushed back and forth between the air duct and the storage chamber. The device filled with a metered amount of active ingredient is emptied in the air duct and then moves back into the storage chamber in order to be filled again with a metered amount of active ingredient by a filling agent. Accordingly, the powder inhaler also has means by means of which the conveying membrane is moved, so that the filled devices with dosed active substance formulation are transported from the storage chamber to the location of the active substance application, the air duct, and from there the empty device back to the storage chamber. A rotor can also be fitted in the nozzle.

Some inhalers have baffle plates and the like, which is somewhere between the capsule chamber and mouthpiece in the flow passage are attached to break up any agglomerates.

In the development of every powder inhaler It must be noted that there is no large deposit of particles can come in the inhaler, its further use for pharmaceutical reasons quality threaten can. Therefore and for an optimal application of the powder formulation to ensure, are the inner surfaces all the parts that can come into contact with the aerosol cloud, especially the pantry and mouthpiece designed particularly smooth.

To contaminate a new aerosol cloud Preventing it with old deposited particles can be beneficial be if the powder inhaler after one or more inhalation procedures (-Vorgängen) is cleaned, especially the parts that come with the powder formulation have come into contact. This cleaning is necessary to get a Pollution next minimize inhaled aerosol cloud, i.e. to improve the pharmaceutical quality of the next to ensure applying aerosol cloud.

Description of the invention

Surprised it has now been found that powder inhalers, in which at least part of the inner surfaces, in contact with the powder aerosol can come, with a micro or nano structured surface are provided, have no poorer application behavior, as powder inhalers with a smooth inner surface in them Areas.

At the same time, such surfaces are Particularly well suited to be easily cleaned with water, since the cleaning liquid drips off the surface and carries away any contamination.

There are none from the prior art Powder inhalers with a micro- or nanostructured surface are known.

It is therefore an object of the present invention To create powder inhalers that are more efficient to clean, without affecting the application behavior of the powder formulation.

Another job is prefers to create such Bernoulli inhalers, i.e. inhalers, which are loaded with a capsule containing the active ingredient formulation includes.

Another job is to overcome the disadvantages known from the prior art.

Detailed description the invention

The powder inhaler according to the invention exists essentially at least from a) a mouthpiece and b) an opening into the mouthpiece Air duct that is equipped with the active substance formulation to be applied can. Optionally includes the powder inhaler optionally with an air inlet channel or an air vent provided chamber for receiving the active ingredient, for receiving a active ingredient-containing capsule, an active ingredient-containing blister pack and / or for receiving a conveyor belt containing active ingredients.

If necessary, there are devices to open the blister or capsules are present.

In the pantry or air duct the drug is mixed with air and through the mouthpiece to the mouth of the user.

Especially in the case of Bernoulli inhalers the air duct connects the chamber to the mouthpiece. In this case the chamber can also have a further air inlet channel or an opening. In the chamber, the Bernoulli inhalers are preferred around a chamber for receiving a capsule (capsule chamber) according to the invention with means to open from the side the capsule is provided. The capsule chamber is designed so that the reservoir capsule used essentially only one movement longitudinal perform can, if an air flow substantially parallel to the longitudinal axis of the capsule passed through the capsule chamber is and has only a small scope along its transverse axis. Such capsule chambers are for Bernoulli inhalers typical. Within the scope of the present invention the chamber can also be referred to as a storage chamber or dosing chamber become.

The powder inhalers known from the prior art have a smooth, unstructured inner surface. The same applies to other elements that can come into contact with the powder aerosol. According to the invention gives way the structure of the inner surface this part of such an unstructured or smooth surface. Under be unstructured or smooth in the sense of the present Invention description surfaces understood that none of the surface structure described in the context of the invention exhibit.

All inhalers described at the beginning in the prior art section can be used for the powder inhalers according to the invention. In order to avoid repetition, the features of these inhalers mentioned at the beginning should not be repeated here, but reference is expressly made to this section. The inhalers of the DE 3345722 , WO 91/02558 or the EP 0911047 , That is, the features mentioned in the introduction to the generally described powder inhalers apply with the exception of the parts that come into contact with the powder aerosol in relation to the design of the inner surface. This also applies to the powder inhaler according to the invention and should therefore not be described here be called again. The capsules mentioned in the same section can be used in a preferred inhaler according to the invention.

In the context of the present invention, the inner surfaces of the parts which come into contact with the powder aerosol, that is to say the surfaces which come into most contact with the powder aerosol, are referred to as the critical surface. The critical surfaces expressly include the mouthpiece and the air duct opening into the mouthpiece. Possibly. can also the inner surface of the lower part or the plate of an inhaler described above according to the EP 0911047 be provided with the structure according to the invention.

In the case of Bernoulli inhalers (see e.g. DE 3345722 , WO 91/02558 or the EP 0911047 ), which are preferred according to the invention, also includes the inner surface of the capsule chamber as the critical inner surface.

In the case of inhalers according to the DE 3348370 . DE 3336486 . DE 4106379 and the US counterparts mentioned below, the chamber for receiving the blister pack can also be added to the critical surface.

In the case of an inhaler that is the entry for the US 4524769 uses the principle described, the pantry can also have a critical surface.

In the case of inhalers with a separator, this may also have such a critical surface. Such a separator is used, for example, in the EP 0633792 described.

According to the invention, at least part of the critical surface of the powder inhalers is provided with a micro or nanostructure. Surfaces with describes a microstructure that has self-cleaning properties EP 72514 to which reference is hereby made.

At least the inner surface of the mouthpiece is preferred 20% of its surface is micro- or nanostructured, stronger it is preferably at least 50%, even more preferably at least 75%.

In the case of Bernoulli inhalers is preferably or at least only the inner surface of the capsule chamber to 20% of its surface micro or nano structured, stronger it is preferably at least 50%, even more preferably at least 75%.

In the case of inhalers with blister packs or Conveyor belts prefers the inner surface into the mouthpiece opening out Air duct at least 20% of its surface is micro- or nano-structured, stronger it is preferably at least 50%, even more preferably at least 75%.

The external design of the parts, which is a critical inner surface have no significant role in the context of the present invention and can be modeled analogously to the devices known from the prior art his. For example, in Bernoulli inhalers the exterior Shape of the capsule chamber due to its location and its possible movements in the inhaler or the movements of other parts of the inhaler determined around the capsule chamber.

The structuring of the critical surface is achieved by at least parts of the critical inner surface Elevations and depressions are formed.

The elevations and deepenings can Shape of tips, spheres, flat surfaces, wedge-shaped, hemispherical, etc. his.

You can use a random arrangement have or be ordered, e.g. in rows, circles, zigzag, meandering etc.

The distance between the surveys the surface structure is in the range of 0.1 to 200 microns, preferably 0.1 to 100 microns. Stronger distances are preferred from 0.1 to 10 microns, the strongest distances are preferred from 0.1 to 1 micrometer.

In order to achieve an optimal spreading of the Particles to ensure should be spacing from 1 to 25 microns can be avoided.

The amount of the surveys or the Depth of the recesses is in the range of 0.1 to 100 micrometers, preferably 0.1 to 50 microns. Distances of are most preferred 0.1 to 10 microns.

The surveys of the surface structures so close together that hydrophilic liquid drops, e.g. Waterdrop, roll on the elevations without really closing the ground touch. At the same time the elevations of the surface structures are not are too close together or the depressions are not too flat, so that in terms of droplet size liquid not a closed surface form where the surface forces between drops and surface come into full effect. The aim should therefore be that as the distance between the surveys increases, so does the height of the surveys should increase from the underground. Surfaces with are preferred Elevations that have 0.1 to 50 microns and where the Distance between the elevations is 0.1 to 100 microns.

The critical ones preferably exist surfaces made of hydrophobic materials or durable hydrophobic materials or they are coated with such materials and the bumps are not removable by water or by water with detergents. As Materials can Plastics, metals, ceramics, glasses etc. are used.

Preferred materials are glass and / or ceramics and / or metals and / or plastics, such as polyethylene, Polypropylene, polycarbonate, polyacrylates, polyester, silanes etc. Plastics are preferred. Possibly. can such a plastic with be provided with a lacquer layer of another plastic, the the surface structure wearing.

Such structured surfaces can be either by making the surface structures already at the manufacture of hydrophobic materials or only afterwards created by subtractive or additive treatment of the surfaces become. These procedures include subsequent Embossing, etching, laser ablation, galvanic removal, sticking a structured film, sticking a powder, spraying with suspensions, separation of sublimates etc.

Finally, it is possible to do such self-cleaning surfaces of objects through subsequent durable waterproofing of previously manufactured surfaces with the desired structures to accomplish.

A possibility for subsequent Durable waterproofing is the subsequent silanization of before manufactured surfaces with the ones you want Structures. Silanization can take place on all materials, which are inherently hydrophilic but are capable of reactive groups of the silanes to react, so ultimately the surface consists of the hydrophobic residues of the silanes.

To the desired surface structures already to create from hydrophobic polymers, the objects be made from the outset in forms that are the negative of the desired surface structure exhibit.

It is also possible to apply the hydrophobic polymers in the form of solutions and / or dispersions which, when they dry and set, lead to the desired surface structures ren.

Such structures arise, for example from self-organizing polymers or under conditions such as they are known in principle from the production of matt lacquer surfaces.

If it is not possible or not desirable, the desired surface structures creating from the start, this can also be done retrospectively, for example by subsequent embossing or etching. Embossing can for example by means of heated or heatable stamps. The etching can take place with the known means of chemical etching or by physical methods such as ion etching with oxygen or others Irradiations that roughen the surface and one that can be used according to the invention surface structure to lead.

The way of a surface texture is created depends of the chosen material and the one you want Microstructure.

It has also been shown that it also possible is the one you want surface structure to be obtained by sticking a powder made of the hydrophobic polymers. Are powders of hydrophobic polymers with the desired grain size available. Optimal results can only be achieved if powder is used with a relatively narrow grain size distribution.

As already described, e.g. the inner surface of the mouthpiece for all types of powder inhalers to the critical surfaces. The shape of the mouthpiece is essentially defined by its function.

The mouthpiece, which is generally tubular, optionally something is flattened, axially or at an angle to the axis the air duct connected to it or arranged to the side be offset from this axis.

In the case of the preferred Bernoulli inhalers heard next to the inside surface of the mouthpiece also that of the capsule chamber to the critical surfaces. Therefore is supposed to be closer at this point these two elements are discussed.

The mouthpiece is the simplest Fall around a tube that is on one side with the capsule chamber in Connection is established and is open on the other side.

It can be designed as a cap which is placed on a lower part of the inhaler, which the Capsule chamber includes. This cap can be placed on the edge of the inhaler housing around a perpendicular to the longitudinal axis of the inhaler horizontal axis be pivoted. Mouthpiece and lower part of the inhaler housing can also by a usual Be plugged together. Due to the solubility or pivoting of the two parts is in any case access overall, on the one hand to the capsule chamber and the cutting device in the lower part of the housing and on the other hand to the internal parts, such as the sieve plate, of the upper housing part (the sipper Cap) considerably simplified.

To exchange the used capsules for In such an embodiment, the unused mouthpiece is folded up or the plug connection between the mouthpiece and the lower housing part is released. The Capsule chamber is then freely accessible, so that the emptied capsule is removed and a filled one is inserted can be. Then the device closed or put together.

The interior design of the capsule chamber is typically such that they are open on two sides Cavity for holding a disposable capsule for pharmaceutically active inhalants having. These two openings are preferably located opposite one another Pages or in their immediate vicinity. The inner shape can e.g. that of a preferably uniform Cylinders or cuboids. The inner shape is preferred based on the shape of a cylinder.

The dimension of the capsule chamber is adapted to that of the capsule. The cavity preferably has one Diameter that is 1.1 to 2.5 times the capsule diameter. The cross section is preferably 1.1 to 2.2 times, in particular 1.2 to Is 1.6 times as large as the capsule diameter.

The length of the inner cavity of the Capsule chamber is 1.02 to 2 times the length of the Capsule, preferably 1.04 to 1.8, especially 1.1 to 1.6 times poured is like length the capsule. The diameter of the chamber should be smaller than the length the capsule so that the capsule in the chamber in the longitudinal direction is held and cannot tip over.

For clarification are the following some examples of typical capsule dimensions given, the conclusions on the size of the Allow capsule chamber.

Total length of the closed capsule: 26.1 ± 0.3 mm; 23.3 ± 0.3 mm; 24.2 ± 0.3 mm; 21.7 ± 0.3 mm; 19.4 ± 0.3 mm; 18.0 ± 0.3 mm; 15.9 ± 0.3 mm; 14.3 ± 0.3 mm; 11.1 ± 0.3 mm.

Outer Capsule body diameter: 9.55 mm; 8.18 mm; 7.36 mm; 7.34 mm; 6.63 mm; 6.07 mm; 5.57 mm; 5.05 mm; 4.68 mm.

Outer Capsule diameter: 9.91 mm; 8.53 mm; 7.66 mm; 7.64 mm; 6.91 mm; 6.35 mm; 5.83 mm; 5.32 mm; 4.91 mm.

The commercial capsules have the so-called size 3 on how it is known at least in Germany. In the described Telescopic capsules the diameter of the upper part 5.83, the diameter of the lower part 5.57 mm.

The capsule chamber has two openings, an inlet for incoming air and an air outlet. The air inlet has a smaller cross section than the capsule chamber, so that a relatively high flow in this area of the capsule chamber air velocity occurs and a powder is applied in the capsule by the Bernoulli effect. The air inlet opening is expediently arranged centrally in the bottom of the chamber.

There can be one on the air outlet side Screen plate or other device such as projecting components, be formed, which prevents that in the capsule chamber moving capsule can block the air outlet or that may resulting capsule fragments into the mouthpiece be sucked.

The sieve plate can e.g. part one funnel-shaped connector be on the beginning of the inhalation channel leading to the mouthpiece it can be attached that the funnel edge with the sieve plate in one Insert plate engages, which forms the bottom of the mouthpiece. The sieve plate can also be clamped between the funnel edge of the connector and a stop of the insert plate can be exchangeably attached.

There can also be multiple openings as an outlet opening be provided. The one for the outflow is the cross section available from the air from the capsule chamber expediently larger than everywhere the air inlet opening, so that the air loaded with the medicine can flow out as freely as possible. The air outlet will be convenient centrally located in the ceiling of the chamber, but can also be placed on the side of which can be arranged in the ceiling area.

By arranging the two openings should an axial air flow, i.e. vertically, through the capsule chamber.

The capsule chamber instructs at least a point along its long axis (related to the interior of the capsule chamber) an opening for or Connection with a) cutting device with at least two pointed needles or cutting is provided to make one in the Prick or cut open capsule chamber. This cutter is against the pressure of a spring inside the chamber slidable and will over a spring-loaded control button served.

Because the height of the capsule chamber depends on the length of the Drug capsules are intended, the tips or cutting edges the cutting device preferably in the area of the upper and lower End of the capsule chamber arranged. The side wall of the capsule chamber can face the needles / cutting edges in the area of their upper and lower ends radial bores or elongated Have slits for the implementations serve the needles / cutting. The dimension of these holes / slots is modeled on the cross section of the needles or sheaths.

In a preferred embodiment of the Bernoulli inhaler according to the invention shows leadership the needles of the cutting device on a sealing plate. On this way the seal between the in inhalation position located capsule chamber and the cutting device improved. For the spring bearing of the sealing plate the spring can be used which is the reset the actuation button the cutting device.

Finally, in another embodiment a lever system for the actuation the cutting device provided. This lever system is preferred from an actuation button attached to the bottom or side of the housing of the inhaler actuated from. The lever system can consist of a rocker and a toggle lever, the actuating button acts on one end of the rocker, and the other end of the rocker presses on one end of the toggle lever, whereby the other end of the toggle lever attached to the cutter advances the cutter. Rocker and toggle are preferred pivoted about axes in brackets attached to the housing are.

The capsule is said to be close to the inhalation process opened at both ends become. The hemispherical caps of the capsule should not be damaged. This is important because the capsule or capsule cap is attached Valve function. Because of the pressure conditions the capsule is against the inflowing Air drawn to the inlet opening and closes it. Since the user continues to suck on the mouthpiece, A negative pressure is created in the capsule chamber, through which the capsule with the inflowing Air is entrained towards the air outlet. The now on Air inlet pressure creates the capsule again to the inlet opening is pulled. The whole process is repeated in quick succession, as long as through the mouthpiece is inhaled, and sets the capsule in strong axial vibration.

Preferred Bernoulli inhalers are those as initially described as embodiments of the DE 3345722 , WO 91/02558 or the EP 0911047 have been described. At this point, the features mentioned in this section are expressly referred to again. The inhaler as described above in connection with the EP 0911047 has been described.

In such inhalers the capsule chamber according to the invention can be designed as a single chamber, analogous to the explanations for DE 3345722 or EP 0911047 ,

The capsule chamber can also be part a capsule chamber magazine, as described in WO 91/02558 becomes.

Such an inhaler has a revolver magazine with a plurality of mostly tubular chambers each equipped with a capsule. The magazine is covered on each of its two open sides by a plate, one plate containing the air inlet opening and axially the other plate containing the air outlet opening. Because the magazine within this Plates is rotatably mounted, one of the chambers can be pivoted between the two openings and thus form part of the inhalation air passage. After completing an inhalation process, the revolver magazine is rotated further until the next chamber comes into the air passage. For example, one of the two plates can be separated from the magazine in order to remove the used capsules from the chambers, or the entire magazine can be removed for refilling, for example.

In such a training of Invention, the revolver magazine is detachably arranged in the inhaler housing. After the capsules in the revolver magazine have been used, you can the complete revolver magazine replaced or new with capsules filled become.

The inhaler housing can be eccentric have arranged pin on which the revolver magazine can be attached is.

To fix the position of the revolver magazine you can do it with the capsule chambers each assigned recesses for one in the inhaler housing Arranged spring-loaded locking bolt provided. The recesses are arranged so that the locking bolt only clicks into place if one of the capsule chambers is exactly between the air inlet and outlet located.

This can ensure that the revolver magazine during the inhalation does not shift. The resilient mounting of the locking bolt should be chosen with regard to the spring constants so that an accidental Rotation of the revolver magazine prevented by the locking, on the other hand with stronger The revolver magazine can be unscrewed from the lock can. Conical designs of the free end of the locking bolt and correspondingly shaped recesses support this.

The locking bolt is preferred arranged coaxially to the air passage channel under the capsule chamber and has a through hole that simultaneously the bottom Air intake forms. The locking bolt is preferably central in the inhaler housing arranged. According to a further embodiment of the invention the locking bolt is loaded by a spring, the other End on one in the inhaler housing solvable attached plug rests, which also has a central through hole has, which is part of the air passage duct.

In a preferred embodiment are the recesses for the engagement of the locking bolt on the bottom in the base plate of the magazine concentric to the air inlet holes of the capsule chambers arranged and like the coat one with the base facing outwards flat truncated cone. So these recesses are involved around conical or funnel-shaped Extensions to the air inlet holes, the extended area is facing the locking bolt. The resulting from enlargement Bevel roughly the bevels on the head of the locking bolt.

In a preferred embodiment have these recesses at the base of the truncated cone, however still in the base plate, a peripheral stop edge on the as an anti-twist device or stop for the head of the locking bolt serves when it is snapped into the recess. Due to the Said stop edge can therefore be seen with the locking bolt engaged stop turning the magazine.

In another embodiment of this embodiment takes the said stop edge only a part or half of the Circumference of the conical recess, that is, the funnel-shaped extension and is arranged so that it turns the magazine when it is locked Locking bolt locks in one direction, in the other direction but allows because there the weird Wall of the funnel-shaped extension the recess merges smoothly into the outside of the base plate.

In a further preferred embodiment only one of the recesses has the entire circumference of the recess engaging stop edge, so that in this recess when engaged Locking pin a rotation of the magazine is not possible. Considered this position one then as the end position of a magazine in which all capsules are consumed are. All other recesses point in this embodiment only the one-sided, i.e. one-way anti-rotation lock on, so that the magazine only ever swings in the direction a capsule chamber with an unused capsule until the previously described end position is reached, in which the Lock completely is. The user then knows that the magazine is made with fresh capsules to be loaded when this last capsule is used up.

In a further preferred embodiment a tongue can be attached to the locking bolt, which extends up to a stop on the inside of the operating button of the cutting device extends when the locking bolt with the revolver magazine removed occupies its upper stop position. The said tongue works in this position as a lock on the cutting device. When the magazine is inserted, the locking pin pressed down again and thus eliminates the lock of the cutter.

Confirmation of the cutter can can also be coupled with the rotary movement of the capsule magazine, so that with a push of a button, first a capsule chamber into the right one Is brought into position and then immediately the cutting device attacks.

If the revolver magazine and the part of the inhaler housing adjoining it are designed to be n-shaped, where n is an integer, the number of the capsule chambers, the side surfaces of the inhaler housing part and the revolver magazine are advantageously aligned when the magazine is in the correct position. One can then determine immediately from the outside whether the chamber is in the air duct defined by the air inlet and the air outlet.

In addition to the inhalers mentioned, the invention can also be used in inhalers as described by DE 3336486 ( US 4627432 . US 4778054 ) DE 3348370 ( US 4627432 . US 540203 ) DE 4106379 ( US 5590645 . US 5860419 . US 5873360 . US 6032666 . US 20020053344 . US 20020066451 . US 6378519 ) or for example the DE 3274065 ( US 4524769 ) are revealed.

Characteristic features of the same can can be found in the prior art section.

The inhaler according to the invention enables the devices known from the prior art a more reliable Application of the drug with lower standard deviations and guarantees a good cleaning of the same.

It was not foreseeable that the structured surface structures the application behavior with elevations and depressions in a powder inhaler Do not adversely change a powder formulation as an aerosol.

In particular, there was concern that solid particles are stronger on a structured surface adhere to a smooth and therefore poorer application the powder inhalers and / or lead to contamination of the surface.

However, it has been shown that the powder particles suitable for inhalation application do not adhere more strongly a microstructured surface adhere as to a smooth and adhering particle, if necessary with water residue can be removed: Impinging Press water drops through the microstructures and tear stuck particles with himself.

Alternatively and / or in addition to the executions the inside or the outside can also be used for powder inhalers the storage capsule with the microstructured surface according to the invention become. Such a capsule is preferably cylindrical with tapered End up. It consists of at least two sub-elements that are telescopic are pushed into each other. These capsules preferably have one longitudinal axis and a shorter one Transverse axis. The longitudinal axis is the axis that is parallel to the generatrix of the cylinder jacket lies. The longitudinal axis is longer than the transverse axis so that the longitudinal section the capsule is oval, the cross-section is circular having.

The at least two are preferred Sub-elements in the direction of the longitudinal axis pushed into each other.

Details of the capsule designs can be found in the prior art section and other places in this description of the invention. In particular, details of the EP 1100474 can be found, to which express reference is hereby made.

Similarly, the blister packs mentioned for the inhalers described above ( DE 3348370 . DE 3336486 . DE 4106379 ) or conveyor belts ( US 4524769 ) be coated on the inside and outside with such microstructured surfaces.

Such blisters can be a blister bed with cup-like Have depressions or troughs, which by an overlying Foil are closed.

With these blisters you can Tubs lie side by side like in a pearl necklace or they are arranged in rows. The blister beds can be made of plastic or an aluminum foil. The same applies to the sealing films.

As materials in the prior art disclosed materials, such as plastics, aluminum foils, etc. used become.

The following is intended to illustrate the invention of examples and drawings to be discribed.

Examples

example 1

A smooth surface Plastic such as Formica or polyethylene becomes uniformly thin with one Spread glue like UHU PLUSs and then with a Teflon powder coated like Hosta flons TF 9205 (average particle size 7 microns). After curing creates a surface from the deposited particles such as soot and paint powder with water rinsed can be.

Example 2

A smooth, hydrophobic material like PTFE is heated until it is plastically deformable. It will now a high mesh screen pressed from the offset printing onto the surface and removed again.

After cooling, a surface is created with regularly arranged Elevations and in-depths of comparable height.

The dimensions can be changed and optimally adjusted by using different sieves with different mesh sizes and thicknesses. The properties of the surfaces obtained in this way are optimal if the elevations have rounded tips. Of course, these surface structures can also be produced by heated embossing pieces or rollers. Ent Talking foils can be stuck on another smooth surface.

Example 3

It becomes the adhesive behavior of fenoterol examined on polyester films with a structured acrylic layer.

Slide 1 has structures in the range of 0.5 micron.

Slide 2 has structures in the range of 2 microns.

Slide 3 has structures in the range of 2 micrometers, with 10 micron superstructure.

An unstructured serves as a reference Polyester film.

The films of Example 3 were each in the lid of a container glued. Defined powder quantities are placed on the film sections of fenoterol of grain size 3.5 to 4.2 microns applied using a cascade impactor. The impactor was operated at a flow rate of 391 / min and the film sections placed on the separation stage 2. This Experimental setup allows specifically defined amounts of powder on the foils Particles whose aerodynamic diameter is approximately 4.3 to 5.2 micrometers is, deposit.

The powder piles are not a monolayer, but an agglomerate of powder particles. The adhesive forces among themselves differ from those between powder and film.

The lid is placed on a container and placed in a centrifuge. By starting at different speeds the powder is detached from the film by the centrifugal force and in a container spun. Then the difference in powder mass in Collecting container and determined on the foil section in the lid.

Result:

If the percentage of powder detached is as Function of the relationship G plotted from centrifugal force to the weight of the powder particles, So this function presents itself as a sigmoid curve, that in the beginning increases sharply to at higher G values to show convergent behavior. The G-value is also a measure of the adhesive force a powder particle on the film surface.

It turns out that the recorded curves for all No significant difference between foils and no difference to observe the unstructured reference material. all Curving is more or less common that the powder first from G values of 200 to 800 begins to detach from the foils. With G values of The percentage replaced is 57000 Powder amount from 47 to almost 60%.

For the

Slide 1 the value is G = 57000 between approx. 49% and 56%,

Slide 2: the value is G = 57000 between approx. 46% and 57%,

Slide 3: the value at G = 57000 is approx. 60%.
unstructured reference film: the value at G = 57000 is approx. 47 to almost 60% From the measured curves, the conclusion follows that on structured surfaces, whose characteristic structure size is smaller than the diameter of the particles, the forces to detach the Particles from the surface are not larger than on an unstructured surface, ie there are no higher adhesive forces that would lead to a stronger deposit.

drawings

1 shows a typical two-part capsule that can be provided with the microstructured surface according to the invention.

2 shows an inhaler in which the capsule according to the invention can be used.

3a to d show a powder inhaler with a revolver magazine in which the capsule according to the invention can be used.

4 shows a powder inhaler with an upper and lower part movable against each other.

The 5 to 9 show examples of surface structures.

1 shows a capsule known from the prior art ( 1 ), consisting of a capsule cap ( 2 ) and a capsule body ( 3 ). It can be seen that the outer diameter of the capsule body is smaller over a wide area than that of the capsule cap. This is particularly evident in the region of the down-to-earth hemispherical end of the capsule body.

Out 2 it can be seen how an inhaler can be constructed, in which an inventive capsule chamber is integrated. In a lower part ( 5 ) with optional two windows ( 6 ) there is a plate ( 7 ) with the capsule chamber ( 4 ) connected is. To open the capsules in the capsule chamber ( 4 ) is the button with two specially ground needles ( 8th ) against the pressure of the spring ( 9 ) is pressed in, thereby cutting or pricking open the capsule in the chamber at two points. When inhaling through the device using the leadpipe ( 10 ) that with the top ( 11 ) is connected, the air gets into the lower part ( 5 ) and from there at the bottom into the capsule chamber ( 4 ). The device is covered by a cover ( 12 ) closed, the foldable with the lower part ( 5 ), the plate ( 7 ) and the top ( 11 ) is connected so that dust cannot enter the device when the lid is closed. In the plate ( 7 ) there may be optional blind hole-like capsule holders. A sieve plate ( 34 ), which at the lower end of the leadpipe ( 10 ) or of the inhalation channel leading to the opening of the mouthpiece and, when the inhaler is closed, the air outlet opening of the capsule chamber ( 4 ) covered. Optional snap hooks on the plate (not shown) 7 ) oriented side of the leadpipe ( 10 ) or the upper part ( 11 ) in the plate ( 7 ) can snap into place. In this case, the plate ( 7 ) correspondingly complementary facilities (recesses or holes). On the plate ( 7 ) projections or snap hooks can also be formed on the side so that the plate ( 7 ) in the lower part ( 5 ) can snap into place. The mentioned devices for locking the mouthpiece ( 10 ) or the upper part ( 11 ) in the plate ( 7 ) or that of the plate ( 7 ) in the lower part ( 5 ) are such that they can be easily separated from individual elements. Furthermore, at the location of the cover ( 12 ) above the button when closed ( 8th ), a nose should be designed so that it fits into a recess on the top of the button ( 8th ) engages and the button ( 8th ) blocked so that the button ( 8th ) cannot be pressed when closed. This prevents the capsule from being accidentally punctured if the capsule is inserted prematurely.

3 : Like from 3a . 3b and 3c can be seen, an inhaler with revolver magazine essentially consists of an inhaler housing ( 5 ) with a mouthpiece ( 10 ) on the side of the upper edge of the inhaler housing ( 11 ) around an axis ( 13 ) is pivotally articulated and a revolver magazine ( 14 ) with the capsule chambers ( 4 ) to hold the capsules. The revolver magazine ( 14 ) is eccentric in the inhaler housing ( 5 ) arranged pin ( 15 ) attachable. After attaching the revolver magazine ( 14 ) the mouthpiece ( 10 ) brought into its normal position - as a cap on the housing; the inhaler is functional. A capsule (not shown) can now be 8th ) can be opened. How out 3c visible, the revolver magazine ( 14 ) in this case 6 chambers ( 4 ) to accommodate the capsules, not shown. The bottom of each chamber ( 4 ) has an air inlet hole ( 16 ) on. Furthermore, the revolver magazine ( 14 ) an axial guide ( 17 ) for the pen ( 15 ).

How out 3d visible, the inhaler is adjacent to the one below the inhalation channel ( 18 ) arranged chamber ( 4 ) the cutting device ( 19 ) over the button ( 8th ) is to be operated. This cutting device ( 19 ) has two needles ( 20 ) in the upper or lower part of said chamber ( 4 ) can be inserted radially, with the revolver magazine outer wall for easier passage of the needles ( 20 ) breakthroughs or weakened areas at appropriate points ( 21 ) having. The needles ( 20 ) are used to open the in the chamber ( 4 ) capsule located near its upper or lower end. The revolver magazine ( 14 ) also has below the holes ( 22 ) conical recesses ( 23 ) into which a locking bolt ( 24 ) can snap in as soon as the corresponding one of the chambers ( 4 ) coaxial with the air inlet or inhalation channel ( 18 ) of the inhaler housing. The locking bolt is on its in the recess ( 23 ) engaging end also conical. At the opposite end it is held by a spring ( 26 ) acted on, which is releasably fastened in the inhaler housing ( 27 ) supports. Like the locking bolt, this plug has a central through-hole that acts as an air inlet ( 25 ) serves.

To prepare the inhaler, with the revolver magazine inserted ( 14 ) one of the chambers ( 4 ) by rotating the revolver magazine into a position in which the bottom hole ( 22 ) or the conical recess ( 23 ) coaxial to the air inlet opening ( 25 ) is aligned. The setting of the chamber ( 4 ) is snapped in by the locking bolt ( 24 ) in the recess ( 23 ) facilitated. After the bolt has snapped in, the air inlet opening is aligned ( 25 ) and the bottom opening ( 22 ) the chamber ( 4 ). The capsule cap stands on the bottom opening ( 22 ) and closes it. By pressing the button ( 18 ) against the force of a spring ( 9 ) the cutting edges ( 20 ) radially towards the chamber ( 4 ) moves, first of all the weakened areas ( 21 ) pierce or enter suitable openings in the side wall of the revolver magazine and finally open the capsule at the top and bottom near its end. The tapered caps of the capsules should not be destroyed because they should have a valve function.

If air is now passed through the mouthpiece ( 10 ) is sucked in, the offset from the bottom openings ( 28 ) of the housing ( 5 ) and the air inlet ( 25 ) into the chamber ( 4 ) Incoming air violently vibrates the capsule, whirls up the powder in the capsule, mixes with it and is finally inhaled. The mouthpiece ( 10 ) is generally tubular, but can also be adapted to the shape of the mouth and flattened. In a modification of the embodiment shown, mouthpiece arrangements which are axial or offset at an angle to the axis of the chamber or laterally to the chamber axis are also possible.

The mouthpiece ( 10 ) with an essentially closed insert plate ( 29 ) be provided. This insert plate ( 29 ) can also have openings. Furthermore, the beginning of the inhalation channel ( 18 ) be covered with a sieve, which prevents the capsule or capsule fragments from inhaling into the inhalation channel ( 18 ) get into the mouthpiece. As an alternative to this, wall projections can be provided at the said location, which retain the capsule. The sieve plate is then preferably in the center of the insert plate ( 29 ) arranged, advantageously in the press fit between a stop encompassing the air passage ( 30 ) the plate ( 29 ) and the edge of a funnel-shaped connecting piece ( 31 ), which at the beginning ( 32 ) of the inhalation channel ( 19 ) is attached so that the funnel edge of the insert plate te ( 29 ) faces and engages with it. The alternatively provided projections can also be arranged there.

In the 4 reproduced embodiment of the inhaler according to the invention consists of the lower part ( 5 ) and the mouthpiece ( 10 ) that are put together. The lower part contains the air intake duct ( 25 ) with the air inlet into the capsule chamber ( 4 ) connected is. The cutting device ( 19 ) is supported by a spring element ( 9 ) held in their normal position. The mouthpiece ( 10 ) contains the capsule chamber ( 4 ). Protrusions protrude into the extension of the capsule space ( 33 ) that limit the scope of the capsule. A sieve plate ( 34 ) prevents, for example, fragments of the capsule from being inhaled. The inhaler can be pressed against the pressure of a spring element ( 35 ) are pressed together axially, the upper edge of the lower part being in the position ( 36 ) reached. In this position, the knives or tips ( 20 ) the cutting device ( 19 ) through the opening ( 21 ) in the capsule chamber ( 4 ) penetrate and then open the capsule fixed there.

To use the inhaler after 4 become lower part ( 5 ) and mouthpiece ( 10 ) pulled apart, the capsule inserted and the two parts of the inhaler put together. After squeezing in position ( 36 ) against the spring element ( 35 ) the cutting device ( 19 ) pressed and released again. Under the pressure of the spring element ( 35 ) the inhaler goes back into the 4 shown starting position above. Now by inhaling through the mouthpiece ( 10 ) the active ingredient formulation is inhaled from the capsule, not shown.

The 5 to 9 show examples of surface structures, the surface structures of the films according to Example 3 being shown.

Slide 1 with structures in the area of 0.5 microns.

Slide 2 with structures in the area of 2 microns.

Slide 3 with structures in the area of 2 microns and 10 microns superstructure.

Claims (17)

Powder inhaler consisting of at least one Mouthpiece one in the mouthpiece opening out Air duct and optionally one with an air inlet duct if necessary or provided with an air opening Chamber for receiving the active ingredient, for receiving an active ingredient Capsule, an active ingredient-containing blister pack and / or for absorption a conveyor belt containing active ingredients, characterized in that at least part of the inner surface of the Mouthpiece the air duct and / or the chamber through elevations and / or depressions with a height / depth are structured from 0.1 to 100. Powder inhaler according to claim 1, characterized in that at least either the inner surface of the mouthpiece, the Air duct and / or the chamber at least 20% of its surface micro- or is nanostructured, more preferred at least 50%, even stronger preferably at least 75%. Powder inhaler according to claim 1 or 2, characterized in that the distances between the elevations and depressions in the range of 0.1 to 200 microns. Powder inhaler according to one of the preceding claims, characterized characterized in that the inner surfaces by hydrophobic materials, such as Glass and / or ceramics and / or metals and / or plastics, such as Polyethylene, polypropylene, polycarbonate, polyacrylate, polyester, Silanes are created. Powder inhaler according to one of the preceding claims, characterized characterized in that the inner surfaces by subtractive or additive treatment of surfaces such as embossing, etching, laser ablation, galvanic erosion, sticking a structured film, sticking one Powder, spraying with suspensions, separation of sublimates. Powder inhaler according to one of the preceding claims, characterized characterized that the powder inhaler is a Bernoulli inhaler is. Powder inhaler according to claim 6, characterized in that that the inhaler has a capsule chamber, which with the in the mouthpiece opening out Air duct is connected. Powder inhaler according to claim 7, characterized in that the capsule chamber has a diameter that is 1.1 to 2.5 times is as big as the capsule diameter and a length that 1.02 to 2 times the length of the capsule. Powder inhaler according to one of claims 7 or 8, characterized in that the powder inhaler is a cutting device having at least two pointed needles and / or cutting edges, wherein the needles and / or cutting through openings in the capsule chamber (s) introduced can be. Powder inhaler according to one of claims 6 to 9, characterized in that the inhaler has a) an upwardly open, cup-shaped lower part, b) a plate which covers the opening of the lower part and perpendicular to the capsule chamber is formed, on the capsule chamber a button movable against a spring is provided, which has two ground needles or blades for opening the capsule, c) an upper part with the mouthpiece and the air channel, which can conduct a powder aerosol connects the mouthpiece with the capsule chamber and d) a cover, the elements a), b) c), and d) being connected to one another by a common hinge element, so that they can be moved in a hinged manner relative to one another. Capsule for a powder inhaler, characterized in that the inner and / or the outer surface of the Capsule by elevations and / or depressions with a height / depth is structured from 0.1 to 100. Blister pack for a powder inhaler, characterized in that the inner and / or the exterior surface the capsule by elevations and / or depressions with a height / depth is structured from 0.1 to 100. conveyor diaphragm for one dosed amount of active ingredient for a powder inhaler, characterized in that the inner and / or the exterior surface the capsule by elevations and / or depressions with a height / depth is structured from 0.1 to 100. Capsule, blister pack or delivery membrane according to one of the Expectations 11, 12 or 13, characterized in that the inner surface is micro- or is nanostructured. Capsule, blister pack or delivery membrane according to one of the Expectations 11, 12 or 13, characterized in that the outer surface is micro- or is nanostructured. Capsule, blister pack or delivery membrane according to one of the Expectations 11, 12, 13, 14 or 15, characterized in that the surface at least to 20% of its surface is micro or nanostructured, more preferably at least 50%, even stronger preferably at least 75%. Capsule, blister pack or delivery membrane according to one of the Expectations 11, 12, 13, 14, 15 or 16, characterized in that the distances between the elevations and depressions in the range of 0.1 to 200 microns lie.