WO2004062640A2

WO2004062640A2 - Capsule for receiving an active substance which is administrable by inhalation

Info

Publication number: WO2004062640A2
Application number: PCT/EP2003/014694
Authority: WO
Inventors: Dieter Hochrainer; Heinrich Kladders; Burkhard Metzger
Original assignee: Boehringer Ingelheim International Gmbh
Priority date: 2003-01-14
Filing date: 2003-12-20
Publication date: 2004-07-29
Also published as: WO2004062640A3; AU2003300220A1; AU2003300220A8; DE10300984A1; CA2513201C; EP1587564A2; CA2513201A1; JP2006517421A

Abstract

The invention relates to a novel capsule for receiving an active substance which is administrable by inhalation. The inventive capsule is preferably used for powder inhalators operating according to Bernoulli's principle.

Description

Capsule for taking up an active ingredient that can be administered by inhalation

The invention relates to a novel capsule for receiving an active ingredient that can be administered by inhalation, which is preferably intended for use in a powder inhaler operating according to the Bernoulli principle.

State of the art

The literature knows several powder inhalers working according to the Bernoulli principle. All have in common that the active ingredient to be dispensed is stored in a mostly cylindrical capsule and this capsule is inserted into a capsule chamber of the inhaler.

A suitable powder inhaler essentially consists of a preferably cylindrical capsule chamber, which is provided with means for opening the capsule from the side, an air inlet opening in the capsule chamber, and an air outlet opening and a mouthpiece downstream of the air outlet opening. The capsule chamber is often also preferably cylindrical, being somewhat longer and somewhat wider than the capsule, so that the capsule can vibrate both axially and radially in it, but remains aligned essentially parallel to the chamber axis. The terms axial and radial are synonymous with vertical (axial) and horizontal (radial) with respect to the orientation of the inhaler, in which the capsule chamber is aligned below the mouthpiece. Axial also stands for an orientation parallel to the longitudinal axis of the inhaler (vertical axis), radial is the direction perpendicular to it. 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 leads to a mouthpiece, being able to conduct a powder aerosol. To dispense the active contents of the capsule, the capsule can first be opened at usually two locations on the longitudinal jacket. The openings are usually located near the two longitudinal ends of the capsule. If an air flow is now generated in the capsule chamber from the air inlet to the air outlet, it leads along the longitudinal axis of the capsule and does two things: First, the capsule is mainly moved along its longitudinal axis by the air flow. It can also vibrate to a small extent. On the other hand, the air flowing along the two capsule openings creates in front of the Capsule openings have a negative pressure in relation to the interior of the capsule, so that the powder in the capsule is entrained by the air flow and atomized in the process.

DE 3345722 discloses such an inhaler comprising two housing elements with a single capsule chamber that can be moved in the axial direction.

WO 91/02558 discloses another inhaler described at the outset, but instead of a single capsule chamber, several capsule chambers are combined in a manner similar to a revolver magazine. The open sides of this magazine are delimited by walls, with the air inlet or

Air outlet is located. This magazine is rotatably mounted in such a way that a capsule chamber is connected to the air inlet, the air outlet and the cutting elements necessary to open the capsule only in a certain position.

EP 0911047 discloses an inhaler with a) cup-shaped lower part which is open towards the top, b) a plate which covers the opening of the lower part and is formed perpendicular to the one capsule chamber, 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 can 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 so that they can be folded against one another.

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

The capsules usually used for such inhalers consist of hard gelatin, but they can also consist of a plastic material. In this connection, reference is made to EP 1100474. The capsules known from the prior art consist of two cup-like parts which can be telescopically inserted into one another, the capsule cap and the capsule body. The outer shape 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 lies parallel to the generatrix of the cylinder jacket. The longitudinal axis is longer than the transverse axis, so that the longitudinal section of the capsule is oval and the cross section is circular. Some of the capsules have a circumferential gap at the interface between the capsule cap and the capsule body, which arises from the fact that the capsule cap always has a slightly larger outer diameter than the capsule body. In this connection, reference is made to EP 1100474 or PCT / EP0207481. If, for example, cross-sectional drawings of the two capsule parts are placed on top of one another, it can be seen that the two outer contours are not congruent.

Description of the invention

Surprisingly, it has now been found that the capsules known from the prior art vibrate differently as a function of their position in the inhaler when there is an inflow of air, and the minimum air flow rate for generating the capsule vibration depends on whether the upper or lower part of the capsule is in otherwise the same conditions Direction of the inflow opening. However, such an uncertainty effect is undesirable.

It is therefore an object of the present invention to provide disposable capsules as an active substance reservoir for powder inhalers, especially powder inhalers, which take advantage of the Bernoulli effect and which behave identically regardless of the positioning. Another object of the invention is to change the known capsules such that the active ingredient application is independent of the top-bottom orientation of the capsule in the capsule chamber.

Another aspect of the present invention is to use such capsules in Bernoulli powder inhalers.

Detailed description of the invention

The disposable capsules according to the invention have a longitudinal and a transverse axis, the longitudinal axis being longer than the transverse axis, i.e. the length ratio of the longitudinal axis to the transverse axis, the elongation, is greater than 1. According to the invention, the outer contour of the capsule is designed with mirror symmetry with respect to a mirror plane Sigma h dividing the longitudinal axis of the capsule. The longitudinal axis is thus perpendicular to the mirror plane. This mirror symmetry does not refer to the inner contour of the capsule. Due to the symmetrization, the inflow and vibration conditions are the same regardless of the direction in which the capsules are introduced into the inhaler. Both show the same flow behavior above the air inlet opening.

In the context of the present invention, the term “mirror symmetry” is not understood to mean an abstract or idealized mathematical operation, but rather the transfer of this mathematical concept to what is physically and technically expedient. As a consequence, the term “mirror symmetry” includes tolerances and blurring that occur eg result from manufacturing reasons.

The term “fuzzy” is understood to the extent to which an element X, which is formed on one side of the mirror plane on the capsule surface, is reproduced identically on the capsule on the opposite side of the mirror plane. The smallest measurable size to which the mirror symmetry is to be applied is 0.15 mm, preferably 0.1 mm, more preferably 0.05 mm. For example, if the capsule surface has punctiform protrusions, a pair of (two) protrusions should still be considered mirror-symmetrical if one protrusion has a diameter of 1 mm and the other (mirror-symmetrical) a diameter of 0.85 mm. In this case, the blur in the sense of the present invention is 0.15 mm, etc.

The fuzzy ones include e.g. also differences of the capsules on both sides of the plane of symmetry as a result of conicity of up to 5 °, preferably up to 2 °, most preferably up to 1 °, as are usually used to detach the capsules from tools.

The term “tolerance” is to be understood as a location. The tolerances are preferably 0 to 0.15 mm, preferably 0 to 0.1 mm, more preferably 0 to 0.05 mm. A capsule is again to be used as an example of the term tolerance with a pair of (two) - in this sense - arbitrarily defined mirror-symmetrical projections.If the one projection is at longitude 0 (analogous to earth measurement), then its mirror-symmetrical counterpart on the other side of the mirror plane may be up to 0.15 mm next to it the longitude to be considered mirror symmetric, in which case the tolerance is 0.15 mm.

Thus, two features forming a pair of mirrors on the capsule surface can have a tolerance and blurring that deviate from the symmetry, each of 0.15 mm, preferably 0.1 mm, more preferably 0.05 mm.

Another tolerance and blurring zone can be advertised above and below the mirror plane. This zone can have a width of up to 2.5 mm above and below the mirror plane, preferably up to 1.25 mm. In it you can find elements, facilities etc. that are not mirror-symmetrical counterparts or none Have a mirror-symmetrical identical counterpart on the opposite side of the mirror plane. This means that there is a zone of up to 5 mm (2.5 mm above plus 2.5 mm below the mirror plane), which is excluded from mirror symmetry. The background is that in this zone, in the case of two-part capsules, the interface between the two capsule parts is preferably located, for example a weld seam, which of course cannot be produced in strictly symmetrical fashion.

In this sense, the interface between the individual capsule elements can also be excluded from mirror symmetry in the narrowest sense with the tolerances mentioned above.

Also excluded from the mirror symmetry is a possible fine structure of the interface, e.g. the fine structure of a weld. Such a seam should be considered approximately as a line, the height of which corresponds to the height of the weld seam.

Elements smaller than 0.1 mm, preferably smaller than 50 micrometers, very particularly preferably smaller than 10 micrometers, are likewise preferably excluded from the mirror symmetry.

The capsule consists of at least two sub-elements which are telescopically pushed into one another. In a preferred embodiment there are exactly two sub-elements, each of these capsule parts representing a cavity with three closed and one open side. The two sub-elements are connected to each other via the open sides. This opening is preferably perpendicular to the longitudinal axis. In this case, the two sub-elements are a capsule body and a capsule cap. The capsules are preferably of a cylinder-like shape.

The sub-elements can be connected to one another by suitable joining methods after the filling process. For example, gluing, banding, shrinking, friction, laser or ultrasonic welding are suitable. Alternatively or in addition to this, the sub-elements can also be connected to one another by means of clips or snap-in devices. In such an embodiment there are one or more locking means on the inner jacket of the sub-element which is pushed over one of the other sub-elements and correspondingly complementary locking means on the outer jacket of the other, complementary sub-element, which are arranged such that they lock into one another when the capsule is closed engage. Such latching means can be projections and depressions which operate in a manner similar to the push-button principle, which can be punctiform and / or circumferentially annular. Arrangements are preferred in which the projections or depressions are each arranged in a ring or spiral around the jacket.

In one embodiment, one or more annular projections are formed on the inner jacket of the cap and the outer jacket of the body in such a way that in the closed state of the capsule there is in each case a projection of one partial element in a recess of the other partial element.

In the embodiments with said annular depressions and / or projections, these can be continuous or interrupted.

The projections and / or depressions are preferably designed such that they are not visible on the outside.

According to the invention, capsules consisting of two sub-elements are preferred. In such cases, the interface can be formed parallel to the longitudinal axis or perpendicular to it. Embodiments with a seam that runs perpendicular to the longitudinal axis are preferred. In this case, the seam between the sub-elements can halve the longitudinal axis or be formed at a point distant from the center.

In the case of two sub-elements, the interface is preferably centered or offset from the center by 0 to 12% of the outer length, preferably from the center by 0 to 10% of the outer length, more preferably from the center by 0 to 5% the outer length offset. In one of the most preferred embodiments, the seam is in the middle or from offset up to a maximum of 3% of the outer length. The seam is most preferably in the mirror plane.

In such a case of two partial elements pushed one inside the other along the longitudinal axis, the seam can be made by any joining method, e.g. Gluing, banding, shrinking, friction, laser or ultrasonic welding can be closed.

In embodiments in which the seam is not in the middle, it can be closed in such a way that the outer jacket is smooth at this point and the joining process does not disturb the mirror symmetry of the capsule. Otherwise the provisions on mirror symmetry and tolerances or unsharpness apply.

The closed capsules according to the invention can have elevations on their outer jacket. These elevations can serve as spacers when the capsule is inserted into the capsule chamber of the inhaler.

The height of the elevations (i.e. the distance from the base point to the apex) is preferably 0.1 mm to 5 mm, more preferably 0.5 mm to 2 mm.

The surveys can e.g. be designed as ribs with abrupt edges, with soft, wavy transitions or as pins. Combinations of these are also possible.

The tips or ridges (edges) of these elevations in the most preferred case have a minimal surface.

In the case of ribs, these can be axial (= vertical), ie parallel to the longitudinal axis of the capsule in the chamber, horizontal or perpendicular to the longitudinal axis of the capsule or skewed 1/1449-FF

Longitudinal axis of the capsule can be arranged. The term "skewed" also includes spirally arranged ribs.

If the ribs are arranged axially, the capsule expediently has at least three or more such ribs. It preferably has no more than nine, more preferably no more than six such ribs. The length of the ribs is selected so that they guide the capsule in the capsule chamber during its axial movement without this movement being blocked. The ribs preferably extend over the entire height of the capsule on its outer casing which is not curved with respect to the longitudinal axis. In this case, the ribs preferably have a triangular cross section, with a tip of the

Triangle away from the capsule surface. This embodiment has the advantage that the capsule can be guided in the capsule chamber during its axial movement without great friction losses. Other geometrical configurations of the ribs are also possible, e.g. Ribs with semicircular, rectangular cross-section etc.

In order to prevent the capsule from becoming jammed in the axially arranged ribs, it can be advantageous if the distance between two adjacent pairs of ribs is different (non-equidistant arrangement of the ribs). In this case, the cross-sectional arrangement is asymmetrical.

If the ribs are arranged horizontally (= perpendicular to the longitudinal axis), at least two ribs are preferred. In cross section, these preferably have soft transitions, i.e. it is a wave-like surface. But they can also be angular, etc.

A further embodiment of the capsule has an outer surface with a wave profile as just described, ribs being formed axially on this surface, ie perpendicular to the waves. These are in turn designed such that the outer edges of the ribs are equidistant from the central longitudinal axis of the capsule, the outer edges the ribs do not have a wavy surface, but an uncurved surface (parallel to the longitudinal axis).

In the case of pin-shaped elevations, these can either be arranged linearly, possibly replacing the ribs, or their arrangement is arbitrary. The pins are aligned so that the axial movement of the capsule can not be disturbed, but the capsule is guided in this movement.

In all of these embodiments, however, the elevations are mirror-symmetrical on the outer surface of the capsule, the mirror plane defined above being used as a basis.

However, a preferred capsule has a macroscopically smooth outer surface, i.e. there are no surveys. The term “macroscopically smooth” is understood to mean surfaces which have elevations and depressions of at most 0.5 mm, preferably up to 0.1 mm, more preferably up to 0.05 mm.

The capsule according to the invention can be circular, oval or n-angular in cross section with n = 3, 4, 5, 6, 7, 8, 9, 10 or more. The cross section preferably has a round or oval shape.

In the preferred case, it is a two-part, telescopically pluggable capsule made of a capsule cap and a capsule body, which, when closed, represents a cylinder with tapered ends, preferably hemispherical ends. The cylinder has a longitudinal axis and a transverse axis. The longitudinal axis is the axis that lies parallel to the generatrix of the cylinder jacket. The longitudinal axis is longer than the transverse axis, so that the longitudinal section of the capsule has an oval geometry and the cross section has a circular geometry. Preferably, such a cylinder, coming from the center, always has a constant external cross section until it tapers continuously in order to form the rounded ends.

Such a cylinder has a jacket that is not curved parallel to the longitudinal axis.

The cylinder can also be concave to the outside, i.e. have bent jacket away from the central axis (= longitudinal axis). Such a concave shell occurs, for example, when the outer diameter of each of the two capsule parts, as viewed from the tapered end, increases steadily.

In an alternative, less preferred embodiment, the outer contour of the jacket is concavely curved.

Finally, the outer shell of each of the two capsule parts, coming from the tapered end, can initially run as a straight line that is parallel to the longitudinal axis before it curves slightly away from the central axis and then continue to run as a straight line, but now in one Angle alpha lies to the central axis until it finally reaches the open end of the capsule part. In this case, the outer contour of the assembled capsule resembles the convex outer contour described above.

The capsule body - or alternatively the capsule cap - can have on the inside of its open end an edge running parallel to the inner jacket, which protrudes beyond the edge of the outer jacket and which can be inserted into the capsule cap and thereby connects the two elements (capsule cap and capsule body) , This creates a circumferential edge on the inside of the jacket, parallel to the opening, onto which the capsule cap is then attached. In other words, the inner casing of this capsule part is drawn higher than the outer casing, so that at the closure point Between the capsule cap and the capsule body there is a step on which the other capsule part is seated in the closed state.

Such a cylinder-like embodiment of the capsule with a macroscopically smooth outer surface and a circular cross section can be considered with regard to the

Ideally, symmetry properties of the outer surface are assigned to the symmetry group D∞ _h . In this case, idealized means that deviations due to production technology are not taken into account and that the definitions of tolerances and blurring as defined above also apply here. Bodies are assigned to this symmetry group with a vertical two-fold axis of rotation (= longitudinal axis), an infinite number of two-fold axes of rotation perpendicular to it and a mirror plane that is perpendicular to the longitudinal axis, ie horizontal. According to the invention, capsules are preferred, the outer contour of which can be ideally assigned to this symmetry group in the sense defined above.

The total length of the closed capsule is preferably 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. The outer diameter of the capsule body and the capsule cap in the region of the closed capsule which is visible from the outside is preferably: 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 dimensions of the capsule according to the invention are modeled on the commercially available capsules of the so-called size 3, as is known at least in Germany. In the telescopic capsules described, the outer diameter is preferably between 5.57 and 5.83 mm.

The capsules should preferably be used in powder inhalers, for example of the type described at the beginning in the prior art section. The inhalers of DE 3345722, WO 91/02558 or EP 0911047 are expressly mentioned. These inhalers are about inhalers that work on the Bernoulli principle (Bernoulli inhalers). These inhalers have a capsule chamber, the cross section of which is 1.1 to 2.5 times as large as the capsule diameter and whose length is 1.02 to 2 times as long as the length of the capsule. The capsule chamber has at least 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 rate occurs in this area of the capsule chamber, which increases the Bernoulli effect, through which the powder in the capsule is ultimately discharged. The air inlet opening is expediently arranged centrally in the bottom of the chamber. A sieve plate or other device, such as projecting components, can be formed on the air outlet side, which prevents a capsule moving in the capsule chamber from slipping into the air outlet and thus blocking it, or from any capsule fragments that may have been sucked into the mouthpiece. The sieve plate can, for example, be part of a funnel-shaped connecting piece which can be plugged onto the beginning of the inhalation channel leading to the mouthpiece in such a way that the funnel edge engages with the sieve plate in an insert plate which forms the bottom of the mouthpiece. However, the sieve plate can also be exchangeably fastened in the press fit between the funnel edge of the connecting piece and a stop on the insert plate. •

A plurality of openings can also be provided as the outlet opening. The cross section available for the outflow of air from the capsule chamber is expediently larger than the air inlet opening everywhere so that the air loaded with the medicament can flow out as freely as possible. The air outlet opening is expediently arranged centrally in the ceiling of the chamber, but can also be arranged laterally in the ceiling area.

The arrangement of the two openings is intended to guide an air flow axially through the capsule chamber. The capsule chamber has at least one point along its longitudinal axis (relative to the interior of the capsule chamber) an opening for or a connection with a cutting device, which is provided with at least two pointed needles or cutting edges, around a capsule located in the capsule chamber pierce or cut open. This cutting device can be displaced into the interior of the chamber against the pressure of a spring and can be operated via a spring-mounted actuation button. Since the height of the capsule chamber is determined by the length of the drug capsules, the tips or cutting edges of the cutting device are also preferably arranged in the region of the upper and lower ends of the capsule chamber. The side wall of the capsule chamber can have radial bores or elongated slots facing the needles / cutting edges in the region of its upper and lower ends, which serve for the passage of the needles / cutting edges. The dimension of these bores / slots is modeled on the cross-section of the needles or cutting edges.

In a preferred embodiment, the guidance of the needles of the cutting device has a sealing plate. In this way, the seal between the capsule chamber in the inhalation position and the cutting device is improved. For the resilient mounting of the sealing plate, the spring can be used, which causes the actuation button of the cutting device to be reset.

Finally, a lever system for actuating the cutting device is provided in a further embodiment. This lever system is preferably confirmed from an actuation button attached to the bottom or side of the housing of the inhaler. The lever system can consist of a rocker and a toggle lever, one end of the rocker acting on the actuation button and the other end of the rocker pressing one end of the toggle lever, the other end of the toggle lever attached to the cutting device advancing the cutting device. The rocker and toggle lever are preferably mounted in brackets which are attached to the housing and can be pivoted about axes. The capsule should be opened near its two ends for inhalation. The hemispherical caps of the capsule should not be damaged. This is important because the capsule or capsule cap performs a kind of valve function. Due to the pressure conditions, the capsule is drawn against the inflowing air 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, by means of which the capsule is entrained with the inflowing air in the direction of the air outlet. The negative pressure now developing at the air inlet causes the capsule to be pulled towards the inlet opening again. The whole process repeats itself in rapid succession as long as the mouthpiece is inhaling and sets the capsule in strong axial vibration.

The powder inhalers equipped with a capsule according to the invention, which in the simplest case consist of a capsule chamber, an air inlet opening, an air outlet opening which is connected to a mouthpiece and a device for piercing the capsules, are also the subject of the present invention.

The air mixed with the drug in the chamber is fed as a powder aerosol through the mouthpiece to the user's mouth. The mouthpiece, which is generally tubular, possibly somewhat flattened, can be arranged axially or at an angle to the axis of the chamber or offset laterally to the axis of the chamber.

The mouthpiece of the inhaler can be designed as a cap which is placed on a lower part of the inhaler, which contains the capsule chamber. This cap can be pivoted on the edge of the inhaler housing about an axis perpendicular to the longitudinal axis of the inhaler. Mouthpiece and lower part of the inhaler housing can also be fastened to one another by a conventional plug connection. Due to the solubility or

Pivotal movement of the two parts is in any case substantially easier overall access, on the one hand to the capsule chamber and the cutting device in the lower housing part and on the other hand to the inner parts, such as the sieve plate, of the upper housing part (the mouthpiece-like cap). To exchange the used capsules for fresh ones, the mouthpiece is flipped up in such an embodiment or the plug connection between the mouthpiece and the lower housing part is released. The capsule chamber is then freely accessible so that the empty capsule can be removed and a filled one inserted. The device is then closed or plugged together.

Compared to the devices known from the prior art, the inhaler according to the invention enables the drug to be dispensed more reliably with a lower standard deviation.

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

In such inhalers there is only a single capsule chamber for receiving the capsule according to the invention, analogous to the explanations for DE 3345722 or EP 0911047.

Other inhalers have a revolver magazine with a plurality of mostly tubular chambers, each of which can be 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. Since the magazine is rotatably mounted within these plates, one of the chambers can be swiveled in 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 to remove the used capsules Removing chambers or the entire magazine can be removed for refilling, for example.

In such a further development of these inhalers, the revolver magazine is detachably arranged in the inhaler housing. After the capsules in the revolver magazine have been used up, the entire revolver magazine can be replaced or refilled with capsules.

The inhaler housing can have an eccentrically arranged pin, onto which the revolver magazine can be attached.

To fix the position of the revolver magazine, it can be provided with the capsule chambers, each with associated recesses for a spring-mounted locking bolt arranged in the inhaler housing. The recesses are arranged so that the locking bolt only engages when one of the capsule chambers is exactly between the air inlet and outlet.

This can ensure that the revolver magazine does not move during inhalation. The resilient mounting of the locking bolt should be selected with regard to the spring constants so that accidental rotation of the revolver magazine is prevented by the locking mechanism, on the other hand the revolver magazine can be unscrewed from the locking mechanism if more force is applied. Conical designs of the free end of the locking bolt and correspondingly shaped recesses have a supporting effect.

The locking bolt is preferably arranged coaxially to the air passage channel under the capsule chamber and has a through hole which simultaneously forms the air inlet on the bottom. The locking bolt is preferably arranged centrally in the inhaler housing. According to a further embodiment of the invention Locking bolt acted upon by a spring, the other end of which rests on a stopper which is detachably fastened in the inhaler housing and which likewise has a central through-hole which is part of the air passage.

In a preferred embodiment, the recesses for the engagement of the locking bolt are arranged on the bottom in the base plate of the magazine concentrically with the air inlet bores of the capsule chambers and are designed like the jacket of a flat truncated cone with the base facing outwards. These recesses are thus conical or funnel-shaped extensions of the air inlet bores, the extended region facing the locking bolt. The bevels created by the expansion correspond approximately to the bevels on the head of the locking bolt.

In a preferred embodiment, these recesses have a circumferential stop edge at the base of the truncated cone shell, but still in the base plate, which serves as an anti-twist device or stop for the head of the locking bolt when it is snapped into the recess. Because of the abovementioned stop edge, the magazine cannot be rotated further when the locking bolt is engaged.

In another embodiment of this embodiment, said stop edge takes up only part or half of the circumference of the conical recess, that is to say the funnel-shaped extension, and is arranged in such a way that it blocks the rotation of the magazine in one direction when the locking bolt is engaged, in the other But direction allows, because there the sloping wall of the funnel-shaped extension of the recess merges smoothly into the outside of the base plate.

In a further preferred embodiment, only one of the recesses has a stop edge which takes up the entire circumference of the recess, so that rotation of the magazine is not possible in this recess when the locking pin is engaged. This position is then considered the end position of a magazine in which all capsules are used up. All other recesses have in this embodiment only the one-sided, i.e. one-way rotation lock, so that the magazine can only be rotated in the direction of the pivoting of a capsule chamber with an unused capsule until the previously described end position is reached, in which the Locking is complete. The user then knows that the magazine must be filled with fresh capsules when this last capsule has been used up.

In a further preferred embodiment, a tongue can be attached to the locking bolt, which tongue extends as far as a stop on the inside of the operating button of the cutting device when the locking bolt assumes its upper stop position when the revolver magazine is removed. In this position, the said tongue acts as a lock for the cutting device. When the magazine is inserted, the locking bolt is pressed down again, thus eliminating the lock on the cutting device.

The confirmation of the cutting device can also be done with the rotary movement of the

Capsule magazine can be coupled, so that with a push of a button, a capsule chamber is first brought into the correct position and then immediately attacks the cutting device.

If the revolver magazine and the part of the inhaler housing adjoining it are designed to be n-shaped, where n is a whole number indicating the number of capsule chambers, then 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 directly from the outside whether the chamber is in the air duct defined by the air inlet and the air outlet.

The invention will be described in more detail below with reference to drawings.

FIG. 1 shows a closed capsule known from the prior art. FIG. 2 shows an inhaler in which the capsule according to the invention can be used.

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

FIG. 4 shows a powder inhaler with an upper part and a lower part which are movable relative to one another.

Figures 6 to 13 show different embodiments of the capsule according to the Invention.

FIG. 1 shows a capsule (1) known from the prior art, 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 than that of the capsule cap over wide areas. This is particularly evident in the area of the bottom, hemispherical end of the capsule body.

FIG. 2 shows how an inhaler can be constructed, in which a capsule chamber according to the invention is integrated. In a lower part (5) with optionally two windows (6) there is a plate (7) which is connected to the capsule chamber (4). To open the capsules in the capsule chamber (4), use the button (8) with two specially ground needles, which is pressed in against the pressure of the spring (9) and thereby cuts open or pierces the capsule in two places. When inhaling through the device through the mouth tube (10), which is connected to the upper part (11), the air gets into the lower part (5) and from there at the lower end into the capsule chamber (4). The device is closed by a lid (12) which is foldably connected to the lower part (5), the plate (7) and the upper part (11), so that dust does not get into the lid when it is closed Device can penetrate. Optionally, blind hole-like capsule holders can be located in the plate (7). A sieve plate (34), which is attached to the lower end of the mouth tube (10) or the inhalation channel leading to the opening of the mouthpiece and which covers the air outlet opening of the capsule chamber (4) when the inhaler is closed, is advantageous. Optional snap hooks are not shown on the side of the mouth pipe (10) or the upper part (11) oriented towards the plate (7), which can snap into the plate (7). In this case, the plate (7) has correspondingly complementary devices (depressions or holes). On the plate (7), for example, protrusions or snap hooks can also be formed laterally so that the plate (7) can snap into the lower part (5). Said devices for latching the mouthpiece (10) or the upper part (11) into the plate (7) or that of the plate (7) into the lower part (5) are such that individual elements can be easily separated again. Furthermore, at the location of the cover (12), which in the closed state lies above the button (8), a nose can be formed such that it engages in a recess on the top of the button (8) and the button (8) so blocked so that the button (8) cannot be pressed when closed. This prevents the capsule from being accidentally punctured if the capsule is inserted prematurely.

FIG. 3: As can be seen from FIGS. 3a, 3b and 3c, an inhaler with revolver magazine essentially consists of an inhaler housing (5) with a mouthpiece (10) which is laterally on the upper edge of the inhaler housing (11) about an axis (13) is pivotally articulated and a revolver magazine (14) with the capsule chambers (4) for receiving the capsules. The revolver magazine (14) can be plugged onto a pin (15) arranged eccentrically in the inhaler housing (5). After inserting the revolver magazine (14), the mouthpiece (10) is brought into its normal position - as a cap on the housing; the inhaler is functional. A capsule (not shown) can now be opened using the button (8). As can be seen from FIG. 3c, the revolver magazine (14) has 6 in this case Chambers (4) for receiving the capsules, not shown. The bottom of each chamber (4) has an air inlet bore (16). The revolver magazine (14) also has an axial guide (17) for the pin (15).

As can be seen from Figure 3d, the inhaler is adjacent to that under the

Inhalation channel (18) arranged chamber (4) the cutting device (19) which can be operated via the button (8). This cutting device (19) has two needles (20) which can be introduced radially into the upper or lower part of the said chamber (4), the revolver magazine outer wall for easier passage of the needles (20) at appropriate points or openings weakened areas (21). The needles (20) serve to open the capsule located in the chamber (4) near its upper or lower end. The revolver magazine (14) also has conical recesses (23) below the bores (22), into which a locking bolt (24) can snap as soon as the corresponding one of the chambers (4) is coaxial with the air inlet or inhalation channel (18) of the inhaler housing , The locking bolt is also conical at its end engaging in the recess (23). At the opposite end it is acted upon by a spring (26) which is supported on a stopper (27) which is detachably fastened in the inhaler housing. Like the locking bolt, this plug has a central through-hole which serves as an air inlet (25).

To prepare the inhaler, with the revolver magazine (14) inserted, one of the chambers (4) is brought into a position by rotating the revolver magazine, in which the bottom-side bore (22) or the conical recess (23) is aligned coaxially with the air inlet opening (25) , The setting of the chamber (4) is facilitated by latching the locking bolt (24) into the recess (23). After the bolt has engaged, the air inlet opening (25) and the bottom opening (22) of the chamber (4) are aligned. The capsule cap stands on said bottom opening (22) and closes it. By actuating the button (18) against the force of a spring (9), the cutting edges (20) are moved radially in the direction of the chamber (4), 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 kind of valve function.

If air is now sucked in via the mouthpiece (10), the air flowing from the bottom openings (28) of the housing (5) and the air inlet (25) into the chamber (4) causes the capsule to vibrate violently, causing the powder to swirl 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.

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

The embodiment of the inhaler according to the invention shown in FIG. 4 consists of the lower part (5) and the mouthpiece (10) which are put together. The bottom part contains the air inlet channel (25) which is connected to the air inlet into the capsule chamber (4). The cutting device (19) is held in its normal position by a spring element (9). The mouthpiece (10) contains the capsule chamber (4). In the extension of the capsule space protrusions (33), which limit the scope of the capsule. A sieve plate (34) prevents fragments of the capsule, for example, from being inhaled. The inhaler can be axially compressed against the pressure of a spring element (35), the upper edge of the lower part reaching position (36). In this position, the knives or tips (20) of the cutting device (19) can enter the capsule chamber (4) through the opening (21) and then open the capsule fixed there. To use the inhaler according to FIG. 4, the lower part (5) and mouthpiece (10) are pulled apart, the capsule is inserted and the two inhaler parts are plugged together. After being compressed in position (36) against the spring element (35), the cutting device (19) is actuated and released again. Under the pressure of the spring element (35), the inhaler returns to the starting position shown in FIG. 4. The active ingredient formulation can now be inhaled from the capsule (not shown) by inhalation through the mouthpiece (10).

FIGS. 5 and 6 each show a mirror-symmetrical capsule (1) according to the invention comprising a capsule cap (2) and a capsule body (3). The inside of the capsule body has an inward-reaching extension (37) which is inserted into the capsule cap. The approximately perfectly hemispherical ends, as shown in Fig. 5, are preferred for hard gelatin capsules. In the case of capsules produced by the injection molding process, the injection points are somewhat recessed at the ends (FIG. 6).

FIGS. 7 a to d show different locking techniques with latching means on the

Capsule cap and the capsule body. In Figures 7a to 7c, the smooth side is the outside. In a variant according to FIG. 7d, the smooth side can be the inside or the outside of the closed capsule. FIG. 7c has snap-type latching means, with a projection (38) on one of the capsule elements and a recess (39) for latching the projection on the other capsule element.

The closure variant according to FIG. 7d has a projection (40).

FIG. 8 shows a variant in which the side wall of the capsule cap (2), when viewed from the open to the closed end, tapers suddenly (41). The capsule body can then only be pushed into the capsule cap until it strikes the taper (41) from the inside. The position of the taper is chosen so that the mirror symmetry of the closed capsule is preserved.

FIG. 9 shows a variant in which the interface between capsule cap (2) and capsule body (3) is not in the mirror plane.

Figure 10 shows a variant with a closure according to Figure 7d.

FIG. 11 shows a variant with a seam running parallel to the longitudinal axis.

FIG. 12 shows a variant according to FIG. 11 with a closure according to FIG. 7d.

FIG. 13 shows a variant with a seam running perpendicular to the longitudinal axis, which is banded (41).

Claims

claims

1. Use of a medicament capsule consisting of at least two parts, which has a longitudinal axis and a transverse axis which is shorter with respect to the longitudinal axis, and which is used to hold an inhalable pharmaceutical active ingredient formulation in

Form of a powder is intended, in a powder inhaler, characterized in that the outer contour of the closed pharmaceutical capsule is mirror-symmetrical with respect to a transverse plane dividing the longitudinal axis, the following features being excluded from the symmetry consideration: - Fine structures of the seams, which are caused by the closing of the seams of the

Individual parts of the drug capsule are produced and / or - elements formed on the capsule surface that are smaller than 0.1 mm, preferably smaller than 50 micrometers, very particularly preferably smaller than 10 micrometers, and / or - conicity of up to 5 °.

2. Use according to claim 1, characterized in that the inhaler is a Bernoulli inhaler.

3. Use according to claim 1 or 2, characterized in that on the

Features located on the capsule surface and forming a pair of mirrors may have a tolerance and blurring deviating from the symmetry of 0.15 mm, preferably 0.1 mm, more preferably 0.05 mm.

4. Use of a medicament capsule according to one of the preceding claims, characterized in that the medicament capsule has elevations on its outer surface.

5. Use of a drug capsule according to one of the preceding claims, characterized in that the drug capsule has no elevations, but has a macroscopically smooth surface.

6. Use of a medicament capsule according to one of the preceding claims, characterized in that the medicament capsule consists of two telescopically insertable parts along the longitudinal axis.

7. Use of a medicament capsule according to one of the preceding claims, characterized in that the medicament capsule has a cylindrical outer contour.

8. Use of a medicament capsule according to one of the preceding claims, characterized in that the medicament capsule has tapered closed ends.

9. Use of a medicament capsule according to one of the preceding claims, characterized in that the seam of the two medicament capsule parts is offset from the center by 0 to 12% of the outer length, preferably by 0 to 10% of the outer length, more preferably by 0 to 5% of the External length and most preferably is formed centrally.

10. Use of a medicament capsule according to one of the preceding claims, characterized in that the medicament capsule can be assigned to the D∞ _h symmetry group with regard to its outer contour irrespective of the interface between the two medicament capsule parts and irrespective of manufacturing deviations.

11. Use of a medicament capsule according to one of the preceding claims, characterized in that the powder inhaler consists of at least two housing parts consists of an upper housing part which is connected to a mouthpiece and a lower housing part with at least one medicament capsule chamber, the medicament capsule chamber (s) having an air inlet opening and an air outlet opening and the air outlet opening (s) via a connection which can conduct an aerosol with is connected to the mouthpiece.

12. Use according to claim 11, characterized in that the drug capsule chamber has a cross section that is 1.1 to 2.5 times as large as the drug capsule diameter and a length that is 1.02 to 2 times as long as the length of the drug capsule.

13. Use according to claim 11 or 12, characterized in that the powder inhaler has a cutting device which is equipped with at least two pointed needles and / or cutting edges, the needles and / or cutting through openings in the drug capsule chamber (s) ) can be introduced.

14. Use according to claim 11 to 13, characterized in that the powder inhaler comprises: 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 medicament capsule chamber of the type described above is one against one on the drug capsule chamber

Spring movable button is provided, which has two ground needles or blades for opening the drug capsule, c) an upper part with a mouth tube, which can conduct a powder aerosol, is connected to the drug capsule chamber and d) a cover, the elements a), b) c), and d) are connected to one another by a common hinge element, so that they can be moved so that they can be folded against one another.

15. Use according to claim 11 to 14, characterized in that the powder inhaler contains a magazine made of drug capsule chambers.

16. Powder inhaler according to one of claims 11 to 15 with a medicament capsule according to one of claims 1 to 10.

17. Medicament capsule, which in the closed state has a longitudinal axis and a transverse axis which is shorter with respect to the longitudinal axis and consists of two telescopically along the

There are parts that can be inserted into one another in the longitudinal axis, characterized in that the outer contour of the closed pharmaceutical capsule is mirror-symmetrical with respect to a transverse plane dividing the longitudinal axis, the following features being excluded from the symmetry consideration: - Fine structures of the seams, which are caused by the closing of the seams of the

Individual parts of the drug capsule are formed and / or - elements formed on the capsule surface that are smaller than 0.1 mm, preferably smaller than 50 micrometers, very particularly preferably smaller than 10 micrometers, and / or - conicity of up to 5 °.

18. Medicament capsule according to claim 17, characterized in that the medicament capsule has the features of a medicament capsule according to one of claims 2, 3, 4, 6, 7, 8, 9 or 10.