Inhaler.

(42) Date of commencement of the patent: 15, 5.1987 (45) Date of issue: 10.12.1987 (73) Patentee:

HURKA WILHELM DR. LIESERBRÜCKE, CARINTHIA (AT). HATSCHEK RUDOLF A. DR. FRIBORG (CH).

(72) Inventor:

HURKA WILHELM DR. LIESERBRÜCKE, CARINTHIA (AT). HATSCHEK RUDOLF A. DR. FRIBORG (CH).

The invention relates to an inhalation device for the metering and distribution of solids, in particular of pharmacologically active substances in the solid state, into the respiratory air, consisting of one with an air inlet (6) and an air outlet (8) provided body (1, 2), in the interior of which a supply of solids is provided and by the flow of the inspired air, a ball (4) is movable, whereby the release of solids is effected. According to the invention it is proposed that the ball (4) is arranged in a self-contained, toroidal and at least approximately circular orbit (3), tangentially connected to the air inlet (6) in connection with air inlet passage (5) connects that with a the air outlet (8) communicating with respect to the orbit (3) Zentripetales Luftausströmsystem (7) is provided, and that the solids to be metered and distributed are distributed between the ball and the raceway surface.

SOLID BODIES IN THE BREATHING AIR

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AT 384 552 tor Bwaas

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The invention relates to an inhalation device for dosing and distribution of solids, in particular of pharmacologically active substances in the solid state, in the breathing air, consisting of a provided with an air inlet and an air outlet body, inside which a supply of solids is provided and by the flow the inhaled air in the body is a ball movable, whereby the discharge of solids is effected.

In the known inhalation device of this type (DE-PS No. 845385) the supply of solids in finely powdered form is provided in a equipped with a sieve bottom capsule, which is inserted into the device such that its lower part in a on the one hand with the air inlet an approximately semicircular curved inlet pipe and on the other hand with the mouthpiece or the like. trained air outlet in communicating chamber protrudes. The ball is arranged in the inlet tube and is moved when inhaled by the flow of inhaled air against the opening into the chamber end of the inlet tube, wherein it abuts the capsule and thus causes a small amount of solids through the sieve bottom of the capsule falls and gets into the airflow.

A disadvantage of this operating according to the salt shaker principle device is mainly that it can be used only for larger amounts of substance, which means that the active substance must be mixed with a large amount of inert substance. It is therefore a very large total amount of air (many breaths) required to transport the relatively large amount of solids. This results in a time-consuming application, which can lead to alarm conditions (asthma) under certain circumstances. Furthermore, the known device of its shape is rather bulky and too large for transport in the bag. Also, the intended for continuous use device is unhygienic, as soon forms a bacterial flora in the air ducts, which leads at least to an odor nuisance. Finally, too many manipulations are needed to prepare an application from the patient, namely the insertion of the capsule containing the solids into the device with prior removal of a cap covering the screen (with the risk of loss of solids through the screen) and compliance with a correct one Device position during inhalation.

The object of the invention is to avoid these disadvantages and to provide an inhalation device, on the one hand so easy and inexpensive to produce that it can be intended for single use, and its construction on the other hand, a realization in pocket size allows, the device from the patient always can be easily carried and is therefore always available when needed.

This object is achieved on the basis of an inhalation device of the type specified in the present invention, that in the body a self-contained, at least approximately circular orbit is provided, in which the ball is captively received, wherein the orbit tangentially connected to the air inlet in connection Air inlet duct connects and provided with the Luftausiaß in connection Luftausströmsystem is provided through which the air can flow centripetally with respect to the orbit, and that the solids to be metered and distributed are distributed between the ball and the raceway surface.

The mechanical principle of action of the device according to the invention is based on the fact that tangentially entering into the orbit air is the ball in circulation by the air intake on the suction or as a mouthpiece formed air outlet, wherein in this ball movement, a range of relative movements between the fixed raceway surface and the arises in all spatial directions rotating spherical surface. These relative motions exert compressive and shear forces on the solids distributed between the ball and raceway surfaces, thereby initiating a comminution process similar to a ball mill combined with an aerosol forming process by dispersing the millbase into the air leaving the orbit through the exhaust system , This charging of the air with the solid particles takes place according to the countercurrent principle, since the solid particles follow the centrifugal force, but the air in the mixing area flows centripetally.

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The structure and operation of the device according to the invention allows small and safe dosable amounts of active substance. It is therefore no substance dilution required. This results in a very rapid effect, with only a small inhalation volume. The device does not require a separate capsule for the active substance and also does not require a specific device position in use, whereby a simple and safe manipulation is given. Due to the almost immediate effect there is no danger of an alarm period. The simple, connected with only low production cost construction of the device allows the determination of the device for single use, which no hygiene problems can occur. Furthermore, the structure of the device allows the realization of the device in pocket size, so that the device can always be easily carried by the patient.

The solids are preferably applied in the form of a film on the ball and / or raceway surface, wherein expediently the ball and / or the raceway surface are structured (thus), whereby a higher absorption capacity of active substance, a simpler application of the active substance and a higher degree of comminution and a better distribution of the active substance in the air can be achieved.

In the preferred embodiment, the body of the apparatus consists of a support in which the orbit, the tangential air inflow duct and the air outflow system are formed, and a cover sheet having the air inlet and the air outlet.

Preferably, the air inlet and the air outlet hiebei are formed as a simple circular air passage openings of the cover sheet.

In order to ensure sterility until use, the body of the device is expediently provided on the cover side with a peel-off film closing the two air passage openings.

The invention will be explained in more detail with reference to the drawings. In these show: Fig.l schematically in longitudinal section a first embodiment of a device according to the invention, the body is formed of a support and a cover sheet, Fig.2 and 3 are plan views of the support and the cover sheet of the device according to Fig.l, Fig.4 on an enlarged scale a Section according to the line IV-IV in Figure 2, Figure 5 shows a second embodiment of the device according to the invention in longitudinal section, wherein the individual parts of the device are shown exploded, 8 shows a schematic sectional view of a part of a prototype of the device according to the invention made for experimental purposes, which has an exchangeable insert body, FIGS. 9 and 10 show the insert body of the prototype according to Fig.8 in view and plan view, and Figs. 11 and 12 in a schematic representation of two deviating from the circular shapes for the orbit of the device.

The inhalation device shown in FIGS. 1 to 3 has a body consisting of a carrier -1- and a cover sheet -2-, wherein the carrier -1- has a material recess which inside the body has a toroidal, circular orbit -3 - for a ball -4-, one to the orbit -3- tangentially adjoining Lufteinströmkanal -5-, which communicates with a the air inlet of the device forming circular air passage opening -6- in the cover sheet -2-, and a Luftausströmsystem -7-, which is connected to a device forming the air outlet of the circular air passage opening -8- of the cover sheet -2- in connection and through which the air with respect to the orbit -3- centripetal can flow out. On the cover side, the body -1,2- with a the air passage openings -6 and 8- tight and sterile-free closing release liner -9- provided.

The tangential Luftteinströmkanal -5- has a smaller depth than the orbit -3-, so that the ball -4- also in the region of the mouth of the channel has sufficient mechanical guidance.

On the surface of the sphere -4- and / or the surface of the orbit -3- is applied in a later still exactly explained manner by the device in the breathing air to be metered and distributed active substance in the form of a film.

The ball -4- has, as shown in Fig.4 made clear to that of a part of the inner surface of the carrier -1- and a part of the inner surface of the cover sheet -2- formed

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Surface of the orbit -3- a defined game, which determines the efficiency of the air drive of the ball and the absorption capacity of active substance.

By taking place during inhalation of air at the air passage opening -8- passes through the tangential air inflow channel -5- air into the orbit -3- and drives the ball -4-. As a result of the ball movement, compression and shear forces are exerted on the active substance present between the ball and the raceway surface in a manner similar to that in a ball mill and the active substance is comminuted. The resulting ground material is thereby distributed in the air leaving the orbit by the Ausströmsystem -7-.

The Luftausströmsystem -7- is formed by the free space between the carrier -1- and the cover sheet -2- in the central region -10- of the orbit -3-. In the illustrated simplest case, this system is an annular gap of uniform cross-section, which is defined on the one hand by the inner diameter of the circular path -D- and on the other hand by the diameter of the circular air passage opening -8-.

An improvement in the drive efficiency can be achieved if the gap cross section is formed non-uniformly so that this cross section in the zone immediately after the entry of the tangential Lufteinströmkanals -5- (zone a in Figure 2) in the orbit is a minimum and then increases steadily, until it becomes a maximum immediately before the air inflow duct (zone b), and then immediately returns to a minimum (zone c). The cross-sectional variation of the system described can be easily achieved by a corresponding design of the central region -10 of the orbit -4-, as will be explained in more detail later in connection with Figures 8 to 10.

The formed of the support -1- and the cover sheet -2- body of the device is suitably made of plastic, for example ABS, wherein the carrier either

a) as injection molded part of plastic granules or

b) is produced as a deep-drawn part of plastic, which is formed after heating over a die.

The practical implementation will certainly be made according to a), since a much higher accuracy can be achieved thereby.

If a production of metal, for example aluminum, is desired, the mold can be formed by stamping or by deep drawing.

The connection of the support -1- with the cover sheet -2- can be done: by ultrasonic welding by Anodic bonding or by gluing, adhesive amount, adhesive pattern / geometry and contact pressure must be designed so that penetration of the adhesive into the dynamic working space of the ball avoided becomes.

The ball -4- is preferably a glass ball.

The surface of the sphere -4- and / or the orbit -3- can be structured in an advantageous manner.

This achieves the following improvements: higher absorption capacity of active substance easier application of the active substance a) on the spherical surface

b) better distribution of the active substance in the air on the surface of the orbit better degree of comminution of the active substance.

The structuring of the spherical surface is given in the simplest way by the manufacturing process. In the preferred use of glass beads, the raw abrasive surface provides good adhesion of the active ingredient, which is applied to the beads by wetting with an active substance solution and then evaporating the solvent.

The spherical surface may also have a golf ball-like structure.

If the surface of the orbit -3- structured and possibly the active substance is applied to the orbit, the glass ball used can be acid-polished.

The surface structure of the orbit is expediently in the form of spiral grooves

No.384552 along the direction of movement of the ball, similar to the swirls in firearms. This structure causes a rotation of the ball perpendicular to the direction of rotation. This is particularly advantageous for substance distribution.

The production of the twist structure poses no problems in fabrication, since it can take place simultaneously with the forming process (injection molding, deep-drawing, embossing) of the orbit. The crushing and distribution function becomes the consideration of the dynamic

Behavior of the orbiting ball on the hand of Fig.4 clear.

1. By the action of the centrifugal force, the ball rolls in contact with the outer ring wall of the orbit -3- (see contact point B). This results in a rotation of the ball about the axis A.

Second A swirl structure of the raceway surface simultaneously causes a rotation of the ball, for example, in the direction of the arrow around the axis C which is perpendicular to the image plane.

Third In the direction of the arrows L, which represent the air flow to the outflow system, the velocity gradient between the ball surface and raceway surface becomes larger and larger, which contributes to good solid-air distribution through turbulence.

With the device according to the invention, all pharmacologically active substances can be administered which are inhalable and are absorbed via the mucous membranes of the respiratory tract. The device is specifically designed for the treatment of asthma and bronchitis with the substances salbutamol and betamethasone. However, it is also thought to administer insulin by means of this device, which can be applied via the nasal mucosa. Other substances that could be administered with the device according to the invention are, for example, epinephrine, ephedrine, isoproterenol, metaproterenol, terbutaline, isoetharine, theophylline and their derivatives, as well as corticosteroids, such as hydrocortisone, or sodium cromoglycate.

There are various ways to dose the active substance and bring it into the device.

1. The active substance is dissolved in a solvent and the sphere is immersed. Evaporation of the solvent leaves a film of solid, crystalline active substance.

Second The solution of the active substance can be introduced into the orbit forming the orbit of the wearer of the device. Drying creates a film of crystalline in the groove

Active substance.

Third The substance is introduced into the device in solid form.

For the special case of salbutamol, 0.16 mg of substance is applied.

If the solvent used could interact with the plastic of the inhaler used (softener release or the like), the device may be vapor-deposited with a metal (gold, silver), rendering it unassailable to the solvent.

By rotating the sphere, the crystalline particles are finely ground and leave the device with a size of 50 - 2 pm.

In the embodiment shown in Figures 5 to 7, the carrier -1- and the cover sheet -2- plastic parts, while the release liner -9- consists of aluminum. In this embodiment, in contrast to the embodiment according to Fig.l to 3, the central region -10- of the orbit -3- formed in its upper part as a truncated cone with a cone angle of 120 ° and extends to the carrier / cover sheet interface approach. For the air outlet forming circular air passage opening has a

Inner diameter of the orbit -3- corresponding diameter, so that the air outlet annular gap between the lower edge of the air outlet opening -8- of the cover sheet -2- and the frusto-conical annular surface of the central region -10- of the orbit -3- is formed. Again, the Luftausströmsystem -7- formed by the annular gap constructed rotationally symmetric, ie, the annular gap has the same cross-section in all segments.

In a typical practical embodiment of the device shown in FIGS. 5 to 7, the length of the device is 50 mm, the width is 22 mm and the height is 4.5 mm. The orbit -3- has a width of 3.1 mm and the glass ball used has a diameter of mm. The diameter of the Luftdurchtritts6 corresponding to the inner diameter of the orbit

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Opening -8- is 10 mm, while the air passage opening -7- has a diameter of 5 mm. Depending on the selected pressure difference and selected ball tolerance, the orbital speed of the ball is between 5 and 50 Hz, which corresponds to 300 to 3000 revolutions per minute.

FIG. 8 shows a section of a prototype 5 composed of three aluminum parts of the device according to the invention. The three parts are a lower support body -la- with circular orbit -3a, an upper cover plate -2a with the air outlet forming circular air passage opening -8a- and a replaceable insert body -11-, whose head -11a- the central region of Orbital -3a and has a frusto-conical surface -11b- which limits the Luftausströmsystem forming annular gap 10 -7a-. This prototype served to different geometric shapes of the central

To test the area of ​​the orbit.

Now, if the frusto-conical surface -lb- edited so that it receives the indicated in dashed lines spiral shape is thereby the cross section of the Luftausströmsystem forming annular gap -7a- of a minimum immediately after the confluence of the tangential

Air inlet duct increased to a maximum immediately in front of the air inflow.

With reference to Figures 9 and 10, in which the insert body -11- is shown in view and plan view, now the production of such a spiral shape of the surface -lb- explained by means of a finger milling cutter. The starting point is a rotationally symmetrical insert body 11, the head of which has the cylindrical-frusto-conical shape 20 indicated in FIG. 9, the cone angle of the frustoconical section being 90 °. If the insert body is now slowly rotated about its vertical axis while the oblique milling cutter is being advanced slowly against the axis of rotation of the insert body while the end mill is rotated by 45 ° (the reference numeral -12- indicates the milling cutter), then the result is a

Rotation of the insert body by 330 °, the said spiral shape of the surface -11b-.

Due to this spiral shape, the cross section of the air outlet annular gap is kept relatively small in the first approximately 120 ° drive phase of the ball, starting immediately after the confluence of the tangential Lufteinströmkanals in the orbit, so that there is no great Abströmmöglichkeit for the drive air, while one of about 200 to 300 ° reaching second phase of the gap cross-section is relatively large, which ensures good air outflow in this phase. The air in the orbit in front of the ball should indeed produce as possible no braking effect. Both of these phases are important for optimal operation of the device:

a) The first phase - low air loss - affects the efficiency of the ball drive. It is indeed aspired to a high circulation speed.

b) The second phase - a lot of air loss - is at the appropriate time for the

Ball drive important, but also very significant for a large aerosol penetration. This is desirable so that with minimal suction pressure a maximum of aerosol can be inhaled.

It has been found that even slightly different forms of the orbit can be useful from the circular shape, since periodic acceleration effects on the ball can additionally cause an improvement of the substance separation from the ball and / or raceway surface and the aerosol formation. Such periodic acceleration forces can be caused for example by an elliptical orbit, but also by 2, 3 or 4 indentations or bulges in a circular path. In all cases, however, the deviations from the circular must not be too large, so that the simultaneous braking effect on the ball is not too pronounced.

In elliptical orbits, a half-axis ratio of the ellipse of about 1.25 has been found to be suitable.

FIGS. 11 and 12 schematically show two examples of recesses or bulges aufwei50 transmitting circular paths, wherein the arrow 13 indicates the inflow direction of the air in the orbit. The deviation from the circular shape denoted d may be about 1/25 of the circular path diameter.

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