Pharmaceutic powder holding container with integrated measuring device and powdered

The subject of the invention is a pharmaceutical powder storage container for dry powder inhalers, used to hold a large number of doses of pharmaceutical powder in stock.

Storage containers for pharmaceutical powder and inhalers are used in particular for the treatment of chronic respiratory diseases. A typical field of application is in the treatment of patients with asthma. In such cases, an amount of powdered medicament which is sufficient for multiple doses is packaged in one pharmaceutical powder container. The pharmaceutical powder container is inserted into the inhaler which provides a stream of air with the medicament sprayed therein for inhalation by the patient. When the inhaler is used properly, the desired amount of medication passes into the patient's bronchi and lungs. As a result of using a pharmaceutical powder container instead of a container permanently placed in in

182 198 halator, the costs of such treatment are reduced, in particular of long-term treatment, since the inhaler can be used repeatedly.

WO-93/03782 discloses an inhaler for dispensing a preferably pulverized inhalation preparation and for providing an inhalation stream, comprising a replaceable pharmaceutical powder container for maintaining a medicament supply for an integrated measuring unit. The metering unit comprises a piston which extends through the reservoir of the pharmaceutical powder container. In the region of its lower end, the piston has a lateral measuring cavity for receiving a predetermined amount of a pharmaceutical powder. As a result of the compression of the plunger, the lower end of the plunger emerges from the container and the measuring cavity with the pharmaceutical powder moves to the region of the inhalation conduit. As a result of the air stream generated by the patient, the pharmaceutical powder is dispersed in the air stream and inhaled by the patient. Additionally, a counting device for an inhaler is also proposed.

However, the described pharmaceutical powder container has the disadvantage that the plunger with the measuring cavity moves through the medicament supply. Therefore, as a result of the abrasive effect of the pharmaceutical powder, there is a risk of the pharmaceutical powder container losing its seal in the region of the plunger barrel and the pharmaceutical powder thereby passing uncontrolled or the plunger becoming difficult to move and thus losing the patient's reliability in dispensing. Additionally, due to the abrasion of the piston and the necessary seals, the pharmaceutical powder container has a relatively complex structure and is therefore expensive to manufacture. Moreover, an inhaler with such a container has the disadvantage that the suction of the air flow through the patient and the actuation of the measuring piston have to be coordinated. If the measuring piston is activated too soon or too late with respect to the suction of the air stream, no pharmaceutical powder will pass into the air stream and thus into the patient, or too little pharmaceutical powder will pass. Older patients in particular, or patients who panic, as is often the case with asthma attacks, are often unable to cope with the necessary coordination of movements.

DE-43 19514 and WO 94/28957 disclose an inhaler which has a volumetric measuring device. The inhaler described has an integrated reservoir for pharmaceutical powder, which reservoir, together with the rest of the inhaler, impacts the distal parts of the inhaler by releasing a pre-tensioned spring device. As a result of the applied impulse, when the container hits the pharmaceutical powder, the powder compresses and the measuring accuracy is improved. As a result of this complicated design, the described inhaler is relatively expensive to manufacture and, as a result, the integrated drug reservoir can only be used once. As a result, the cost of appropriate therapeutic treatment increases significantly.

DE-42 11 475 describes an inhaler which comprises a replaceable medication magazine which contains multiple doses of medication in single chambers. The individual compartments of the drug magazine empty one after the other. The described inhaler also comprises a dispersion device in which the pharmaceutical powder is ground and dispersed in the stream of inhalation air in the cyclone chamber due to kinetic energy. Additionally, the air stream which is loaded with the pharmaceutical powder is surrounded by an air stream which is free of the pharmaceutical powder to prevent the pharmaceutical powder from settling in the mouth or throat area. Although the described inhaler is intended for multiple use, it is relatively expensive due to its complex design. The disposable drug magazine is also relatively expensive as it contains a large number of individual parts and is difficult to fill due to the large number of drug reservoir chambers.

WO 92/18188 discloses a medicament container and dose metering mechanism for a multi dose dry powder inhaler for dispensing high and low doses of a medicament. The operation of the described mechanism is based on filling the recess in the circular cross-section of the shaft with a dose of powdered medicament by turning

182 198 surrounding the shaft of the medicament container about the shaft and in the inhalation conduit adjacent to the dose by pushing the shaft out of the medicament container. The filling of the recess is accomplished by a sweeping member attached to the container which moves around a shaft with the medicament container. The shaft is preferably fixed to the body of the inhaler, and the medicament container can be replaced by opening the inhaler and pulling the container from the shaft. Filling the container with the medicament can be done through one of the openings on the shaft of the medicament container. In order to allow the correct operation of the described inhaler, the level of the medicament in the medicament container is below the position of the shaft.

EP 0 546 996 A2 discloses an inhaler with an integrated drug reservoir chamber and a U-shaped measurement slide containing a measuring port for measuring a dose of a drug from the container. The U-shaped measurement slide is integrated into the inhaler housing and is manually operated by the user on the side of the inhaler where the inhalation mouthpiece is located.

U.S. Patent No. 5,161,524 discloses an inhaler having an integrated reservoir chamber to receive a dry powdered compound. The inhaler further comprises an actuator with an orifice to discharge a metered dose of the dry powder into the air flow upon actuation, and a one-way flap valve to prevent backflow of air containing the powder dose through the air passage. Both the reservoir chamber and the actuator assembly are integral parts of the inhaler and neither is replaced or refilled.

The object of the invention is to provide a removable pharmaceutical powder container that will reduce the cost of therapeutic drug use and provide simple and reliable operation even for patients with poor coordination and such patients who are under extreme stress.

A pharmaceutical powder storage container for dry powder inhalers, intended to store a supply of medicine sufficient for a large number of doses of pharmaceutical powder, equipped with a pharmaceutical powder reservoir and an integrated measuring unit, containing at least one measuring cavity for holding a predetermined amount of pharmaceutical powder, and a measuring slide measuring the dose pharmaceutical powder from container, displaceably disposed between at least the filling position and the emptying position, according to the invention, characterized in that the measuring slide is provided below the pharmaceutical powder container in position, wherein the pharmaceutical powder is able to flow from the space of the reservoir into the measurement cavity of the measurement slide as a result of gravitational forces and is slidably positioned between the at least two positions approximately transversely to the flow direction of the pharmaceutical powder from the reservoir to the measurement cavity.

The measuring slide is slidably placed into the transport position and fixed in the transport position by means of a spring-elastic unit.

The reservoir comprises a cover inserted into the upper edge of the reservoir and enclosing the reservoir space containing a plurality of doses of pharmaceutical powder, the side wall of the reservoir tapering into a funnel shape with an outlet opening in the lower region, and further comprising a holding assembly for holding the measurement assembly at the lower end. a tank; and a purge unit for supplying purge air, which purge unit is disposed on the outside of the side of the tank, facilitating complete emptying of the measuring cavity of the measuring assembly in the emptying position.

The holding unit for holding the measuring unit comprises a channel which is arranged under the lower end of the tank and in which the measuring slide is movably arranged, so that in the filling position of the measuring slide, the measuring cavity is located in the area of ​​the outlet opening and in the position of emptying the measuring slide, the measuring cavity is located in area of ​​the purifying unit for supplying air

182 198 of the purging unit to facilitate complete emptying of the measuring cavity and in the region of the discharge opening corresponding to the purging unit.

The measurement slide channel is laterally open for a large part of its length transversely to the direction of movement of the measurement slide, so that the actuating device can laterally grasp and move the measurement slide.

The measuring cavity of the measuring slide is located outside the areas of the outlet opening and the cleaning unit in the transport position of the measuring slide.

The measurement slide has a U-shaped cross-section formed by the legs, and on the outside of these legs there are recesses for the actuating unit which extend through recesses in the side walls of the measurement slide channel, and the measurement slide has at an end distant from the measurement cavity a protruding element pointing towards bottom with a limiter that enters the appropriate slot that runs in the longitudinal direction of the base of the tank, as well as a wedge groove for the ear, placed opposite the canal and entering the top wall of the canal.

The outer edge of the tank is higher than the upper edge of the tank, moreover, the tank has a cover with a connecting piece which, when the cover is inserted, fits closely to the upper edge of the tank, and the outer edge of the cover, outside the connecting piece, passes through the upper edge of the tank and an annular gap to the shoulder from the inside of the outer edge of the reservoir and is recessed into this outer edge of the reservoir.

The cover, the measuring slide and the reservoir are manufactured with the integrated measuring unit of thermoplastic material as separate parts without the measuring slide.

The tank has a viewing window at the bottom for checking the position of the measuring slider.

Integrated into the upper edge area of ​​the reservoir is a display unit for informing about the number of doses of medicament removed or remaining in the reservoir.

The display unit is in the form of a strip of foil or a ring movable along the periphery of the upper edge region of the container.

The foil strip or ring is provided with teeth.

In the region of its upper edge, the tank has an annular gap into which a foil strip or a ring is received.

The outer edge of the reservoir, radially delimiting the annular gap to the outside, has a viewing window-shaped recess in at least one place of its circumference, showing a strip of foil or a ring from the outside.

The annular gap is open downwards at at least one point on its circumference through which a drive pulley for the foil strip or ring protrudes downwards.

The display unit is equipped with a scale for determining the number of doses of medicament that have been removed or that remain in the reservoir.

For particularly good handling of the pharmaceutical powder container, it is advantageous before insertion into the inhaler if the measuring slide can also be moved into the transport position, in particular if the measuring slide is fixed in the transport position thanks to an elastic-elastic unit. If the medicament container according to the invention is to be removed from the inhaler although it has not yet been completely empty, it is useful if the medicament container has a viewing window on its lower side through which the position of the measuring slide can be checked. Particularly for patients for whom a medicament which is packaged in a pharmaceutical powder container has a vital meaning, it is useful if the pharmaceutical powder container of the invention can be distinguished by a display unit for the number of pharmaceutical doses that have been removed or remain in the pharmaceutical powder container. pharmaceutical powder, with the team showing for the number of doses of the drug, which have been removed or remain integral with the upper edge region of the pharmaceutical powder container.

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The container cover, the measurement slide and the pharmaceutical container with an integrated measurement unit without the measurement slide can be manufactured as separate parts from a medically acceptable thermoplastic material. Particularly suitable thermoplastic materials are those that can be formed by injection molding, for example polyethylenes, polypropylenes, polycarbonates, polyurethane, polyacrylate, polystyrene, copolymers of acrylonitrile, butadiene, styrene. However, it may also be advantageous to use different plastics for single parts, for example a container and a measuring slide.

The construction of an integrated measuring unit with a measuring slide that can move forward and backward has proved to be reliable in use for many common medical doses of a powder supply, which can be 200-300 doses, in exceptional cases up to 500 doses, inside the container. The base of the container, which has a relatively thin structure and which is connected to the top wall and to the bottom of the container at multiple points to form the channel, eliminates the possibility of the measuring slide snapping tightly into the channel due to the spring effect. In order to avoid tilting of the measurement slide in the channel during operation, said measurement slide is guided on both sides and activation fingers overlap the measurement slide simultaneously on both sides.

The pharmaceutical powder container according to the invention can be manufactured in a particularly simple and cost-effective manner, allows for particularly efficient packaging of the drug stock and is suitable for disposal after a single use. After replacing the pharmaceutical powder container, the inhaler can be used again.

The subject of the invention is shown in the embodiment in the drawing, in which Fig. 1 shows a pharmaceutical powder container according to the invention in a vertical section, Fig. 2 - a vertical section through a powder container along the line N-0 in Fig. 1, Fig. 3 - a sectional view along line GH in Fig. 1 through a pharmaceutical powder container in top view, Fig. 3a - a section along line EF in Fig. 2 through a powder container in its lower region above the measuring unit, Fig. 4 - cross-section along line JK in fig. 1, fig. 5 - cross-section through the lid of a pharmaceutical powder container, and fig. 6a - top view of the measuring slide, fig. 6b - longitudinal section of the measuring slide, fig. 6c - bottom view a measuring slide, and Fig. 6d is a cross-section.

Figure 1 shows a vertical section view of a pharmaceutical powder container 100 containing a multi-dose powdered medicament reservoir 101. For much of its length, the tank has a circular cross-section which is flattened on both sides as seen in Fig. 3 and is a horizontal section along the line GH in Fig. 1. The side wall of the tank 101 has two straight parts of side walls 101a that lie opposite each other and two curved parts of side walls 110b that connect said straight parts of side walls 101a. On one side of the connecting points of straight and curved sidewall portions 101a, 101b are guide ribs 117 which point outwards to form an overall cross section of the container 100 allowing the container 100 to be inserted into the dry powder inhaler only in a predetermined position. In the region of the top edge 102, the reservoir 101 has a circular cross section and can be closed by a cover 121 that can be inserted into the top edge 102. In the lower region 104, the reservoir 101 tapers to a sleeve shape and ends with an outlet 105. Straight portions of the side wall of the reservoir 101 extend linearly as legs 110c in the lower region outside the sleeve 104a as shown in Figs. 2 and 3a.

To deliver an energy pulse to the lower portion of the container 100 by impact during the metering procedure, the leg 116 extends outward in the lower region 104 from the outside of the sleeve 104a in a radial direction of the container to the outer circumference of the container. This arrangement is also seen in Fig. 3a.

An integrated measuring device 107, 123 is disposed on the base 107 of the container 100. Between the bottom surface of the container 101 and the base 107 of the container is a channel 108 for a horizontally movable measuring slide 123, which, together with the base 107,

182 198 forms the measuring unit 107,123. The upper side of the channel 108 is covered on one side of the sleeve 104a by a wall 131 which extends from the outside of the sleeve 104 at the lower end up to the center of the periphery of the container 100 and around which the legs of the measurement slide 123 have a U-shaped cross section.

In the base 107 on the outside of the sleeve 104a there is, on one side, a discharge opening 109 which extends downwards and outwards and which corresponds to an opening 110 for purifying air in the upper wall of the measurement slide tube 108. The opening 110 is the end of the air tube 111 located therein. outside the reservoir 101 in the region of the sleeve 104. This conduit 111 is also shown in Fig. 3a. To form said conduit 111, two legs 11a, 11b, laterally delimiting the conduit 111, extend from the outer wall of the sleeve 104 parallel to the extended portions of the side wall 10lc. The conduit 111 is open to the outside of the container.

The upper edge 102 of the reservoir 101, shown in Figures 1 and 2, of the container 100, extends the curved portions 110 of the reservoir 101 and widens the straight portions 110 of the reservoir so as to form a circle as shown in Figure 2. The top edge 102 of the reservoir 101 is surrounded by the outside. a short distance by an annular outer edge 103 which is spaced from the sidewall of the tank 101. The outer edge 103 is higher than the edge 102 and extends beyond it and has a small shoulder internally to receive the outer wall of the cover 121. A strip of plastic film (not shown) that indicates the units of measurement can be inserted into the ring-shaped space 112 which is open at the top between the outer edge 103 and the top edge 102. The annular gap 112 may then be closed by a cover 121 which is shown in section in Fig. 5 and the outer edge of which has a diameter corresponding to the inner diameter of the outer edge 103 by application of a cover. The foil strip is thus protected against falling out or being removed.

The outer edge 103 has at one point a viewing window 113 through which the position of the foil strip provided with the markings can be viewed from the outside. The outer part of the outer edge 103 is preferably profiled over at least a portion of the circumference to aid in holding and gripping the container 100 when inserting it into the dry powder inhaler.

Figure 2 shows the container 100 in a longitudinal section along the line N-0 of Figure 1, showing the distance between the portions of the sidewall 10a of the container 101 which is smaller in this direction due to the deviation of the cross section from a circular shape. In the region of the top edge 102 of the tank 101, the inside diameter is increased between the wall portions 100a so that the cross section of the tank 101 is circular. The sections 110a opposite the sidewall of the tank 101 are offset towards the interior below the edge 102. The circumferential outer edge 103, together with the annular gap 112 for receiving the foil strip is shown in another view. The cross-sectional view shows that the arm that connects the outer edge 103 to the sidewall 101 of the tank 101 has at one point in the region of the wall portion 10a a downwardly facing hole 114 which extends into the annular gap 112 into which the transport gear wheel enters. for a horizontal displacement of an inserted foil strip, which for this purpose has, for this purpose, on the lower edge, for example, teeth which can engage the teeth of a transport gear wheel.

The sleeve-shaped structure of the reservoir 101 in the lower region 104 with the outlet 105 can also be seen in the view in Fig. 2. The outlet 105 is preferably oval with a longer diameter extending transversely to the direction of the longitudinal channel 108 of the measuring slide. This allows for the production of larger measuring cavities in the measurement slide 123, the available offset of which between the filling position and the emptying position is limited by the external dimensions of the container 100 due to the fact that the measuring cavity 124 cannot be in any way open to the discharge opening 105 and at the same time the discharge opening 109. The channel 108 has a U-shaped cross-section and the legs 115 lie directly

182 198 of the reservoir 101. The bottom wall of the channel 108 of the measurement slide that connects to the legs 115 is also the base 107 of the container.

Figure 4 shows a cross-section along the line JK in Figure 1 and explains the complex shape of the channel 108. The outer walls of the two legs 115 of the channel 108 have recesses 118 which allow a firm locking entry of the actuator assembly on the measurement slide 123 and allow it to be displaced horizontally. The height of the channel 108 may be modified in the manufacture of the container 100 by modifying the distance from the base 107 in the mold. As a result, the volume of the measuring cavity 124 in the measurement slide 123 can be modified in addition to the horizontal dimension of the measurement 124 and can be adapted to the desired measurement quantity.

Figures 6a to 6d show the structure of the measurement slide 123 in a top view (a), a longitudinal section (b), a bottom (c) and a cross section (d). The oval measurement cavity 124 is positioned transversely to the longitudinal direction in the end region to receive a dose of powdered drug from the reservoir 101 of Figures 1 and 2 in a position where the measurement cavity 124 aligns with the outlet 105 of the container 100. A projection 125 with a downwardly directed stop 130 to enter the slot 119 of the base 107 is provided at the opposite end of the gauge slide 123. On the upper edge of the projection 125 is a transversely extending wedge-shaped shallow groove 126 in which the lug (not shown) is The top wall of channel 108 is spring-lockable to fix the measurement slide 123 when the container is filling and during transportation. On the two long sides of the measurement slide 123 there are recesses 127 for the fingers of the powder inhaler measurement lever provided to move the measurement slide 123. On the underside of the measurement slide 123 there is a small, striped elevation around the measurement cavity 124 protruding towards the protruding element 125, with two parallel stripes to reduce the support surface of the measurement slide 123 on the base of the channel 108 and to facilitate the movement of the measurement slide 123. This bulge further seals the measuring cavity 124 against the channel 108 under the measuring slide 123 and reduces the risk of powder entering the channel 108 from the measuring cavity 124 under the measuring slide 123.

6d shows the U-shaped profile of the measurement slide 123, the upward legs 129 of which are intended to ensure that the measurement slide 123 is guided accurately in the channel 108 shown in Figs. 1, 2 and 4. Figs. 6b and 6c also show directed faces. downward stop 130. Measure ram 123 may be moved in channel 108 between three positions. In the transport position, the measurement slide 123 is inserted as far as possible into the channel 108, and the top ear of the channel 108 engages the keyway 126 on the projection 125 of the measurement slide 123 and holds the measurement slide 123 tightly in the transport position. This position is fixed when inserting the measurement slide 123. In this position, the measuring cavity 124 of the measurement slide 123 is approximately coextensive with the outlet 105 of the reservoir 101 for the medical powder.

In the filling position, the locking attachment of the ear to the keyway 126 is released and the measurement slide 123 is slightly laterally displaced in the channel 108 such that the outlet 105 of the reservoir 101 aligns with the measurement cavity 124 of the measurement slide 123 to receive the powder. . This position of filling the measuring slide 123 is achieved for the first time after inserting the canister 100 into the powder inhaler.

The emptying position of the measuring slide 123 is achieved during the measuring procedure by further moving the measuring slide 123 laterally to a position where the measuring cavity 124 aligns with the discharge opening 109 in the base 107 and the purge air opening 110. In this position, a metered amount of powder can be transferred through the opening 109 to the adjacent powder line of the inhaler.

A three-piece pharmaceutical powder container 100 with a base 107 and cover 121 is preferably made of polystyrene, and a measurement slide 123 that can be inserted into the channel 108 is preferably made of polypropylene. The dose removal display unit which is similarly integrated with the container 100 due to the particular design of the area

182 198 of the upper edge of the tank 101 also includes an additional strip of plastic foil or a ring, injection molded with markings, the lower edge of which is serrated. Such labeled foil strips can be easily extruded from the plastic foil. When the container 100 is collapsed before filling and insertion of the lid 121, the foil strip is inserted into the annular space 112 such that the display unit shows the 0 dose units removed in the viewing window 113. When the dose is removed, the belt rotates about the longitudinal axis of the container due to the gear that engages the opening 114. As soon as the preselected number of doses has been removed from the container 100 and transferred to the dry powder inhaler, a marking visible in the viewing window 113 of the outer edge 103 indicates the upcoming complete emptying of the pharmaceutical powder from the container 100, so that the powder inhaler is required to be replaced in order to function properly. powder inhaler. Instead of numbers, deletion can also be indicated visually by a color difference.

After the measuring cavity 124 in the measuring slide 123 has emptied through the discharge opening 109 into the powder line 15 of the powder inhaler, the measuring slide 123 must return to the measuring position. A suitable unit for this is housed in the dry powder inhaler and consists of parts that are separate from the container.

As a result of the structure of the channel 108 with side recesses in the legs 115, actuation of the measurement slide 123 before insertion into the inhaler is difficult, especially since the transport locking of the measurement slide 123 on the ear of the upper wall of channel 108 must first be released. , and only it is necessary to insert through recesses in the side walls of the channel up to recesses on the side surface of the measurement slide.

The lid 121, flush-mounted with a firm fit, cannot be removed without damage and protects the contents of the container from removal or contamination.

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Publishing Department of the Polish Patent Office. Circulation of 60 copies. Price PLN 4.00.