POWDER INHALATOR AND CORRESPONDING METHOD OF ADMINISTRATION

Abstract: A powder inhalator (1) comprises a space (3) for storage of a dose of a pulverous agent and a passage (7) extending from the space (3) to an outlet (8), a valve assembly (4, 5, 6, 10) disposed at least partially in the passage (7) to keep the passage (7) closed except if a dose of the agent is intended to be carried out through the passage (7). The valve assembly (4, 5, 6, 10) opens when a predetermined negative pressure is generated in the portion of the passage (7) extending from the valve assembly to the outlet (8) by the inhalation of a patient. Also disclosed is a corresponding method of administration of a pulverous agent to the lungs of a patient.

Description: POWDER INHALATOR AND CORRESPONDING METHOD OF ADMINISTRATION FIELD OF THE INVENTION The present invention relates to an inhalator for adducing a pulverous agent to a patient, in particular to an inhalator comprising a space arranged for storage a pulverous agent dose and a passage extending from said space to an outlet from the inhalator. The present invention also relates to a corresponding method of administration of a pulverous agent to the lungs of a patient . BACKGROUND OF THE INVENTION U.S. Patent No. 5,320,714 discloses an inhalator for pulverous agents comprising for feeding of a dose of the pulverous agent to a space. This space is in contact with a passage opening to an outlet extending through a mouthpiece. A problem that may arise when using such an inhalator is that the pulverous agent is carried directly with the negative pressure developing in the passage when the user inhales from the inhalator' s mouthpiece. If the user is unable to inhale forcefully enough a moderate negative pressure only is formed in the passage, and an air flow of low velocity is formed carrying with it the pulverous agent. In such case there is a risk of a non negligible amount of the powder dose adhering to the throat of the user or in the mouthpiece of the inhalator. In such circumstances the amount of powder reaching the user' s lungs will be substantially lower than the intended dose. Another serious risk resides in powder adhering to the walls of the passage may come off during a later inhalation event and be carried to the lungs thus producing an overdose of the agent. By U.S. Patent No. 5,297 542 is known an inhalator arranged for adducing a liquid agent in aerosol form. The inhalator comprises valve means opening upon a user creating a negative pressure in a mouthpiece. According to one of its embodiments the inhalator comprises a valve arrangement provided with a piston being displaced against the effect of a return spring. The piston comprises a magnet which, in a displaced state of the piston, affects a magnetisable valve body, thereby displacing the valve body to an open position. In this open position a dose of the liquid agent can be conducted past the valve arrangement and be mixed with an air flow for further transport in aerosol form through a passage to an outlet in the mouthpiece of the inhalator. This valve arrangement is of complex design and occupies a major portion of the space in the inhalator. The aforementioned return spring is only dimensioned to move the piston back to an inactive position. The force exerted by such a return spring is so small that it essentially cedes upon a negative pressure arising in the passage. Neither is such a valve arrangement directly applicable to an inhalator for adducing of a pulverous agent. In order to be able to reach the alveoli it is also important for the particles of the agent to be of a small size . The pulverous agents used in the art may be stored in inhalators in form of loosely compacted balls or similar comprising a single dose to facilitate their handling and to prevent the small particles therein from sticking to the container walls caused by, in particular, static electricity. To form an aerosol from such loosely compacted powders requires a more forceful action of an air stream on them than in case of non-compacted powders. But even in the latter case there are aggregations of particles kept together by weak van der Waals forces or, in addition, electrostatic forces, which have to be disintegrated to form a perfect aerosol. Their full disintegration requires forceful agitation normally accomplished by turbulent air flow with high shearing forces. The generation of a turbulent air flow impacting on the compacted or non-compacted pulverous dose however necessitates the design of the inhaler to be correspondingly adapted. This is not easily done without sacrificing constructional simplicity and adding cost. A further aspect of inhalation therapy with aerosols concerns the influence of air flow and particle size on the deposition of the particles along their path of inhalation. From a medical standpoint it is generally preferred to maximise alveolar particle deposition. The finite size of the particles however makes them differ from the behaviour of their carrier medium which is air. The coarser the particles the greater is their tendency to be deflected towards the walls of a multiple bending path of air flow by inertia. Thus particles or particle aggregates of a small size are advantageous from an administration standpoint. There are, however, technology barriers in regard of producing very small particles and of breaking up particle aggregates of a small size. To reduce unwanted particle deposition along the path the flow rate is limited by restricting air flow through the inhalator. This restriction, on the other hand, impairs the disintegration of compacted and non-compacted pulverous doses in the inhalator. OBJECTS OF THE INVENTION An object of the present invention is to provide an inhalator of the aforementioned kind ensuring a correct dose of the pulverous agent being provided to the user at each dosing event. Another object of the invention is to provide an inhalator of simple design which efficiently disperses compacted or non-compacted pulverous agents in an restricted air stream to form an aerosol of good quality. A further object of the invention is to provide a method of administering to a patient a single dose a pulverous agent by an inhalator. Further objects of the invention will become evident from the following short description of the invention, the description of preferred embodiments thereof, and from the appended claims . SHORT DESCRIPTION OF THE INVENTION The present invention is based on the insight that a high air flow is needed for the disintegration of compacted or non-compacted pulverous agents to form an aerosol of good quality whereas the transport rate of that aerosol to the alveoli of the patient must be kept low to minimise the deposition of aerosol particles along the path of transport. According to the present invention is disclosed a powder inhalator of the aforementioned kind, comprising a chamber in which a single dose of a compacted or non-compacted pulverous agent is disposed, the chamber having an aerosol outlet and an air inlet, the inhalator being provided with valve means preferably disposed between the dose and the outlet opening at a predetermined negative pressure generated by an inhalation of the patient, the valve means being arranged to be kept in the open position during the inhalation once the valve has been opened, thereby generating a predetermined first air flow rate through the valve means to form an aerosol bolus comprising the single dose, and a second air flow rate determined by the inhalation rate of the patient, the first flow rate being substantially greater than the second. Preferably the first flow rate is twice as high as the second flow rate or higher. This arrangement provides for a high initial air flow rate necessary for the disintegration of compacted and non-compacted pulverous agents, while providing for a lower air flow rate for the transport of the aerosol thus formed to the alveoli, which second rate reduces deposition of particles along the path of transport. Preferred opening pressures range from -100 to -350 mm of water column. Since the lung capacity even in most patients with asthma or other lung disease is at least 1 litre and the bolus volume obtained at the preferred opening pressure with state of the art inhalators will be in the order of 100 ccm it is evident that the aerosol bolus requires substantial inspiration following its formation to be transported to the site of desired action, the alveoli. More particularly, according to the invention is disclosed an inhalator of the aforementioned kind comprising a valve assembly disposed at least partially in the passage and arranged to keep the passage closed except when the pulverous agent is intended to be expelled through the passage, the valve assembly being arranged to open when a negative pressure of predetermined size is generated in the portion of the passage extending from the valve assembly to the outlet. Such a valve assembly will open only upon the user generating a sufficient negative pressure in the passage by forceful inhalation. Thereby a high speed of the pulverous agent when leaving the inhalator is ensured, while the risk of a portion of the pulverous agent adhering to surfaces along its path of transport is eliminated. Particularly advantageous is a non-return type valve means to prevent humid exhaled air from inadvertently reaching the pulverous agent. According to a preferred embodiment of the present invention the valve assembly comprises a valve element disposed displaceably between a closed position and an open position. Such a valve element can be designed to utilise the force of said negative pressure to obtain its displacement movement to an open position upon a certain level of negative pressure being reached. The valve assembly can comprise first means for keeping the valve element in a closed position by a force corresponding to the negative pressure level in the passage. Such a force ensures that the valve element will not be displaced to an open position prior to the negative pressure having reached the predetermined level. It is advantageous for the force keeping the valve element in a closed position to immediately cease to act on the valve element upon displacement of the latter from its closed position. Thereby the valve element can be displaced very quickly from a closed position to an open position. Thereby the velocity of the pulverous agent will be retarded only negligibly during the opening period of the valve element and be carried practically unimpeded with the air flow formed by the predetermined negative pressure. According to another preferred embodiment of the invention the valve element is arranged around link means when moving between a closed position and an open position. Thereby the valve element is provided with a simple and reliable design. Such link means may comprise a hinge in form of die cast hinge parts arranged in the passage and adapted to accept taps arranged on the valve element. Preferably the valve element has the form of a substantially flat plate. Such a plate can be adapted to extend over the entire passage in a closed position, thereby forming an airtight closure of the passage. To provide for a good seat in closed position the valve element can abut against at least one support area. Such a support area may extend at least along an edge of the valve element. Preferably the support area extends around the entire circumference of the valve element. This facilitates the valve element ensuring an air tight seal in a closed position. An airtight seal is necessary to protect the pulverous agent from humidity, which might be adduced by air penetrating into the interior of the inhalator, and to ensure that the pulverous agent does not leak to the environment. In still another advantageous embodiment of the invention said first means comprise at least one magnetic material adapted to co-operate with a magnetisable material. For instance, the valve element can comprise magnetic material, and the support area can comprise the magnetisable material. Such a valve element can comprise o an injection moulded polymer material containing magnetic particles, and the support area can comprise a metal plate. Alternatively the valve element can comprise a magnetisable material whereas the support area comprises the magnetic material. The magnetic force acting between the valve element and the support area is dimensioned so as to correspond the predetermined level of negative pressure in the passage at which the valve element is arranged to open. According to a further preferred embodiment of the invention the valve assembly comprises other means arranged to deflect the valve element in the direction of a closed position upon equilibration of the negative pressure. These other means can comprise a spring element which may be arranged so as to act at the linkable fastening or, alternatively, are arranged so as to extend from and act between the valve element and the support area. The spring force of the spring element is substantially smaller than the force exerted on the valve element when the latter is opened. The retarding effect of such a spring element on the valve element at the latter' s opening thus can be disregarded from. Alternatively the other means can comprise a valve element arranged for being displaced back to a closed position by its own weight. By, for instance, arranging the link of the valve element in an appropriate manner the valve element can be brought to reach an unstable position when in an open position, at which position it seeks by its weight to be brought back to a closed position. The sudden thrust of air generated by the valve element opening at the predetermined pressure enhances the formation of an aerosol from the pulverous agent dose stored in the inhalator. The negative pressure at which the valve opens is preferably from -100 cm of water column to - 350 cm of water column. An opening pressure of about - 250 cm of water column is preferred. According to the present invention is also disclosed a method for administration of a single dose of a pulverous agent to a patient, the method comprising: - providing a single dose of the agent in a compartment in a powder inhalator comprising valve means opening at a predetermined negative air pressure disposed downstream of the compartment and a mouthpiece disposed downstream of the valve means; - making the patient inhale through the mouthpiece to generate a negative pressure sufficient to open the valve, thereby forming an aerosol bolus from the powder at a first air flow rate; - making the patient continue to inhale for a period of time sufficient to transport the aerosol bolus to the lungs at a second air flow rate; the first air flow rate being substantially higher than the second air flow rate. Air flow rates are those measured at the outlet of the mouthpiece. The first air flow rate, which, by definition, is the rate measured immediately after the valve has been fully opened, is preferably at least twice as high as the second air flow rate, which is measured at mid-inhalation. It is important for the valve to be of a design making it to fully open once the opening pressure has been reached, and to stay in a fully opened position during the remaining inhalation period. SHORT DESCRIPTION OF THE DRAWINGS In the following preferred embodiments of the invention will be described by reference to attached raw figures, showing Fig. 1 an inhalator according to a first embodiment of the invention in a closed position, in a longitudinal section; Fig. 2 the inhalator of Fig. 1 with the valve assembly in an open position, in the same view as in Fig. 1; Fig. 3 an inhalator according to a second embodiment of the invention with a valve assembly in a closed position, in a longitudinal section; Fig. 4 the inhalator of Fig. 3 with the valve assembly in an open position, in the same view as in Fig. 4; DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION In Figs. 1 and 2 is shown an inhalator according to a first embodiment of the invention. The inhalator 1 is designed with an inner space 2 arranged for storing and enclosing a pulverous agent. The space 2 also comprises a dosing unit not shown in the figures, since such dosing units . are known, and the construction of such a unit is not comprised by the present invention. The aim with the dosing unit is to feed, if so required, a dose of the pulverous agent to a separate chamber 3 in the space 2. The chamber 3 is only shown schematically in the Figures, and may have a design and a position different from those shown in the Figures. By, for instance, a channel the chamber 3 is arranged to be in contact with the surrounding air to make the pressure of surrounding air prevail in the chamber 3 and to make it possible for an air flow being generated through the inhalator at the inhalation of a dose of the pulverous agent. Such a channel is not shown in the figures since the construction of such a channel is not comprised by the present invention. The chamber 3 is disposed adjacent to a valve element 4 which can swivel between an open position and a closed position around a link or axis 5. The valve element 4 has the form of a substantially flat plate, and may consist of an injection moulded polymer material containing magnetic particles. The valve element 4 is arranged to rest, in a closed position, against at least one shoulder comprising a support area 6; it is of a non- return clack type. Alternatively the support area 6 may extend around the circumference of the entire valve element 4. For instance, the support area 6 can comprise a disc of a magnetisable material. On the one hand, the purpose with the support area 6 is to provide a stable support for the valve element 4 and, on the other hand, to keep the valve element 4 in its closed position by a magnetic force of predetermined size. In an injection- moulded valve element 4 containing magnetic particles the magnetic force is evenly distributed, whereby the valve element 4 can be kept in a closed position by a substantially constant magnetic force along its entire area of abutment against the support area 6. Downstream of the valve element 4 the inhalator comprises a passage 7 opening into an outlet 8 provided with a mouthpiece 9. Upon a need to use inhalator according to the present invention arising the user brings the mouthpiece 9 to its mouth. By a vigorous inhalation the user the sucks out the air resident in the passage 7. If this inhalation is not vigorous enough the valve element 4 will not be displaced from its closed position by reason of being kept in place against the support area 6 by the aforementioned magnetic force. Only if the user generates a negative pressure of a predetermined size in the passage 7 exerting a force on the valve element 4 exceeding the retaining magnetic force the valve element 4 swivels around the link 5 from its closed to its open position. Substantially immediately upon the contact of the valve element 4 with the support area 6 is broken the magnetic force keeping the valve element 4 in a closed position ceases to act. In such case the valve element can swivel very rapidly around the link 5 to an open position shown in Fig. 2. By a relatively large negative pressure being required to be generated in the passage 7 prior to the valve element 4 opening an air flow of high velocity through the passage 7 is formed during the opening phase. The pulverous agent is carried by the air flow past the valve element 4 through the passage 7 to the outlet 8 in the mouthpiece 9. Since a negative pressure is also prevailing in the mouth, the throat and the lungs of the user, the pulverous agent is carried from the inhalator' s outlet 8 down to the user's lungs with a high velocity. By the pulverous agent being transported all the time with a high velocity from the chamber 3 of the inhalator 1 to the user's lungs the risk of a portion of the pulverous agent getting stuck along the path of transport, which would result in an insufficient amount of the pulverous agent reaching the lungs, is eliminated. Another risk with the pulverous agent becoming stuck in the passage 7 resides in it possibly coming off during a later inhalation event, thereby providing the user' s lungs with an exaggerate amount of the pulverous agent on that occasion. Upon the dose of the pulverous agent leaving the inhalator it is important that the valve element be again brought back to its closed position. This can be effected by, for instance, a spring element acting between the valve element and the support area. Such a spring element requires only a small force to bring the valve element back to a closed position and, therefore, will not show a noticeable retarding effect on the valve element 4 when the latter is being brought to its open position. When the valve element reaches its closed position the magnetic coupling between the valve element 4 and the support area 6 magnetisable material is formed anew. It is important for the valve element 4 to abut fully sealingly against the support area 6 to prevent humidity from being adduced by air penetrating into the inhalator. Humidity may cause caking of the pulverous agent. Figs. 3 and 4 illustrate an inhalator with an alternative valve assembly. In this embodiment the valve element 4 comprises an extension 10. According to this embodiment the valve element 4 comprises magnetic material in this extension 10 only. The valve element 4 is swivelingly arranged about a link or axis 5 disposed substantially at the transition between the valve element 4 and the extension 10. This link 5 is fastened at a portion of the passage 7 being a lower portion when the inhalator is being used. A recess 11 is arranged to allow the swivelling movement of the extension 10 to the closed position of the valve element 4. In the recess 11 is arranged a support area 6 of a magnetisable material in form, for example, of a metal plate. In the closed position of the valve assembly shown in Fig. 3 the magnetic extension 10 of the valve element 4 is in contact with the magnetisable support area 6. The valve element 4 is kept in this closed position by the magnetic force acting between the extension 10 and the support area 6. To bring the valve element 4 to an open position a negative pressure of a certain level must be generated in the passage 7, this negative pressure being of a size affecting the valve element 4 with a force larger than the retaining magnetic force. When such a negative pressure is generated in the passage 7 the valve element' s extension 10 is swivelled from its contact with the support area 6, whereat the magnetic force between them ceases to act substantially immediately. As shown in Fig. 4 the valve element 4 swivels with high velocity towards its open position. Upon the pulverous agent having passed the valve element 4 and the negative pressure having been equilibrated the valve element 4 again tends to move towards its closed position. This is due to the extension 10 being heavier than the rest of the valve element 4, whereby the valve element 4 is swivelled around the link 5 towards its closed position by gravity. In a fully closed position the magnetic contact between the extension 10 and the support area 6 is established again. The invention is by no means delimited to the embodiments shown in the Figures but can be varied at will within the scope of the patent claims. For instance, it is possible for a valve element being kept in a closed position by a mechanical coupling which releases the valve element 4 only upon the aforementioned negative pressure in the passage 7 being reached. Neither need the valve element be arranged swivellingly but might, for instance, be arranged lb displaceable within the passage 7, the passage in this context being designed so as to allow the pulverous agent to flow past the valve element 4 in its open position. Neither need the valve element be disposed immediately adjacent downstream of the chamber 3 but can be arranged at any desired location along the extension of the passage 7.

Claims: C l a i m s 1. A powder inhalator (1) for adducing a pulverous agent, comprising a space (3) arranged for storage a dose of the pulverous agent and a passage (7) extending from said space (3) to an outlet (8) of the inhalator (1), the inhalator (1) comprising a valve assembly disposed at least partially in the passage (7) and arranged to keep the passage (7) closed except if a dose of the pulverous agent is intended to be carried out through the passage (7), the valve assembly being arranged so as to open the passage (7) when a negative pressure of a predetermined size is generated in the portion of the passage (7) extending from the valve assembly to the outlet (8) . 2. The inhalator of claim 1, wherein the valve assembly comprises a valve element (4) movably disposed between an open position and a closed position. 3. The inhalator of claim 2, wherein the valve assembly comprises first means arranged for keeping the valve element (4) in a closed position by a force corresponding to said negative pressure level in the passage (7) . 4. The inhalator of claim 3, wherein the force keeping the valve element (4) in a closed position ceases to act substantially immediately on the valve element (4) when the latter is displaced from its closed position. 5. The inhalator of any of claims 2 to 4, wherein the valve element (4) is swivellingly arranged around a link (5) at its movement between a closed position and an open position. 6. The inhalator according to any of claims 2 to 5, wherein the valve element (4) comprises a substantially flat plate. 7. The inhalator according to any of claims 2 to 6, wherein the valve element (4) abuts against at least one support area (6) in a closed position. 8. The inhalator according to any of claims 3 to 7, wherein said first means comprises at least one magnetic material arranged for co-operation with a magnetisable material to keep the valve element (4) in a closed position. 9. The inhalator according to claim 8, wherein the magnetic material comprises permanently magnetic material. 10. The inhalator according to claim 7 or 8, wherein the support area (6) comprises magnetisable material. 11. The inhalator according to any of claims 8 to 10, wherein the valve element comprises magnetic material. 12. The inhalator according to claim 11, wherein the valve element comprises an injection moulded polymer material containing magnetic particles. 13. The inhalator according to any of preceding claims, wherein the valve assembly comprises second means arranged for moving the valve element towards a closed position when the negative pressure ceases to act. 14. The inhalator according to claim 13, wherein the second means comprise a spring element. 1 o 15. The inhalator according to claim 13, wherein the second means comprise an arrangement of the valve element (4) of a kind that the element is moved towards a closed position by its own weight. 16. A powder inhalator for administering a single dose of a pulverous agent to a patient, comprising a chamber in which a single dose of a compacted or non-compacted pulverous agent is disposed, the chamber having an aerosol outlet and an air inlet, the inhalator being provided with valve means opening at a predetermined negative pressure generated by an inhalation of the patient, the valve means being arranged to be kept in the open position during the inhalation once the valve has been opened, thereby generating a predetermined first air flow rate through the valve means to form an aerosol bolus comprising the single dose, and a second air flow rate determined by the inhalation rate of the patient, the first flow rate being substantially greater than the second. 17. The inhalator of claim 16, wherein the first air flow rate is at least twice as high as the second air flow rate . 18. The inhalator of claim 16 or 17, wherein the valve means are disposed between the dose and the outlet. 19. The inhalator of any of claims 16 to 18, wherein the valve means are of a non-return type. 20. A method for administration of a single dose of a pulverous agent to a patient, the method comprising: - providing a single dose of the agent in a compartment in a powder inhalator comprising valve means opening at a predetermined negative air pressure and a mouthpiece disposed downstream of the valve means; - making the patient inhale through the mouthpiece to generate a negative pressure sufficient to open the valve means, thereby forming an aerosol bolus from the powder at a first air flow rate; - making the patient continue to inhale for a period of time sufficient to transport the aerosol bolus to the lungs at a second air flow rate; said first air flow rate being substantially higher than said second air flow rate. 21. The method of claim 20, wherein the valve means are disposed downstream of the compartment. 22. The method of claim 20 or 21, wherein the first air flow rate is at least twice as high as the second air flow rate.

Inventors: EWERLOEF GOERAN, EWERLOEF, GOERAN
Applicants: EWERLOEF GOERAN, MEDIFRONT AB, EWERLOEF, GOERAN
Application year: 1999
Main classification: A61M15
IPC codes: A61M15