WO2001062323A1

WO2001062323A1 - Powder inhalator and corresponding method of administration

Info

Publication number: WO2001062323A1
Application number: PCT/SE2001/000314
Authority: WO
Inventors: Göran EWERLÖF
Original assignee: Medifront Ab
Priority date: 2000-02-24
Filing date: 2001-02-14
Publication date: 2001-08-30
Also published as: SE0000603D0; AU2001232587A1

Abstract

A powder inhalator (1) for pulverous agents comprises a means for providing a single dose of the agent in a passage (3, 5, 4) extending from an inlet to an outlet. A valve assembly in the passage (3, 5, 4) is arranged to keep the passage closed except if a negative pressure of a given size is generated in a portion (5, 4) of the passage (3, 5, 4) downstream of the valve assembly. The valve assembly comprises a valve element (6) displaceable between a closed position and an open position in which it restricts the flow of air in comparison with the flow prevailing immediately upon the opening of the passage. Also disclosed is a corresponding method of administration.

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 an inhalator comprising a space arranged for storage a pulverous agent dose and a passage extending from said space to an outlet. 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 for feeding 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.

U.S. Patent No. 5,297 542 discloses 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 lungs of a 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.

Still another object of the invention is to provide an inhalator which controls the flow rate of the aerosol in the bronchi to minimise the adhesion of aerosol particles to the bronchi walls.

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.

Additional 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 rate 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 disposed between the inlet and the dose 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 at a given negative (suction) pressure 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 a powder inhalator for adducing a pulverous agent to a patient by a flow of air, comprising a space for storing a dose of the agent in communication with a passage extending from an inlet to an outlet, the inhalator further comprising a valve assembly in the passage arranged to keep the passage closed except on inhalation when a dose of the pulverous agent is carried through the outlet, the valve assembly being so arranged as to open at a given negative pressure prevailing in a portion of the passage extending from the valve assembly to the outlet, the valve assembly comprising a valve element displaceable between a closed position and an open position in it restricts the flow of air in comparison with the flow prevailing in the passage immediately upon opening of the passage

Such a valve assembly will open only when the user generates 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 reduced or even eliminated Particularly advantageous is a non-return type valve means to prevent humid exhaled air from inadvertently reaching the pulverous agent

According to a first preferred aspect of the present invention the valve assembly comprises a valve element disposed displaceably between a closed position and an open position The valve assembly is designed to release the valve element from a closed position upon a certain level of negative pressure being reached in the portion of the passage disposed downstream of the valve element The valve assembly comprises means for keeping the valve element in a closed position by a force corresponding to the (negative) pressure level in the passage This 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 practically 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 By this 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 a second preferred aspect of the invention the valve element is arranged to swivel around a shaft axis between a closed position and an open position The valve element is of a simple and reliable design, preferably it has the form of a substantially flat plate made in one piece with the shaft 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 the closed position the valve element can abut against at least one support Such a support may extend at least along an edge of the valve element Preferably the support extends around the entire circumference of the valve element This facilitates the valve element forming an air tight seal in a closed position The airtight seal protects 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 a third advantageous aspect of the invention the means for keeping the valve element in a closed position 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 can comprise the magnetisable material The valve element of the invention can comprise an injection moulded polymer material containing magnetic particles, and the support can comprise a metal plate Alternatively the valve element can comprise a magnetisable material whereas the support comprises the magnetic material The magnetic force acting between the valve element and the support 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 fourth preferred aspect of the invention the valve assembly comprises valve element retracting means arranged to displace the valve element to its closed position at the end of inhalation The valve element retracting means can comprise an extension or compression spring element of metal, rubber, etc.. The spring force of the spring element is selected to be 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 valve element retracting means may 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.

According to another preferred aspect of the invention are arranged valve element repelling means, in particular repelling means of a magnetic kind operating in an open position of the valve element. The valve element repelling means are operative over a short distance from the open position valve seat only; their purpose is to equilibrate air flow following bolus formation. They act against the valve element seeking to abut the open position valve seat. The more vigorously the patient inspires the closer will the valve element be drawn towards the open position valve seat. Thereby the free area for passage of air will be reduced at this seat, and less air will be allowed to pass. This self- regulating mechanism enhances repeatable dosing.

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 a particularly preferred aspect of the invention the valve element restricts the air flow in its open position in comparison with the flow immediately after the opening of the valve element. Thereby the transport velocity of the bolus in the bronchi down to the alveoli can be controlled and an excessive velocity be prevented. The reason for this control is the fact that the probability of solid particles suspended in a gas flowing in a curved tube or similar to impinge on the wall of the tube increases with the velocity of the gas. The particles of the powderous agent dispensed by an inhalator suspended in the air flowing down the bronchi thus will run a greater risk of impinging on the wet walls of the bronchi and sticking to them, which will reduce the amount of useful medicament reaching the alveoli. The extent of restriction can be easily determined by experiment. It is advantageous to additionally provide a means for stabilising air flow velocity under conditions of varying inhalation (suction) force exerted by the patient, that is, to counteract a too vigorous inhalation by the patient which would result in an excessive air flow velocity.

According to the present invention is also provided a method of the aforementioned kind, comprising making a person inhale through an inhalator to create a negative pressure sufficient to open a valve upstream of a single dose of a pulverous medicine disposed in the inhalator, thereby creating an air flow sufficient to form an aerosol bolus of the medicine; upon the formation of the bolus, restricting the air flow to protect medicine particles of the bolus from impinging on the airways mucosa during inhalation. It is preferred for bolus formation velocity to be at least twice as high as the transport velocity of the bolus down the airways. It is also preferred to stabilise the bolus transport velocity by arranging a self-regulating valve in the inhalator.

SHORT DESCRIPTION OF THE DRAWINGS

The present invention will be more fully explained in the following by reference to a preferred but not limiting embodiment thereof illustrated in a number of drawings, showing

Fig. 1 an inhalator of the invention with the valve assembly in a closed position, in a longitudinal section C-C (Fig. 2); Fig. 1a a partial view of the inhalator of Fig. 1 , in the same section as in Fig. 1 ; Fig. 2 the inhalator of Fig. 1 , in a transverse section A-A (Fig. 1 );

Fig. 3 the inhalator of Fig. 1 with the valve assembly in an intermediate position, in the same view as in Fig. 1 ; Fig. 4 the inhalator of Fig. 1 with the valve assembly in a closed position, in the same view as in Fig. 1 ; Fig. 5 the inhalator of Fig. 1 , in a transverse section B-B (Fig. 1 );

Fig. 6 the inhalator of Fig. 3, in a transverse section B-B (Fig. 1 );

Fig. 7 the inhalator of Fig. 4, in a transverse section B-B (Fig. 1 ).

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT OF THE INVENTION

Figs. 1-7 of the drawings show an inhalator 1 according to a preferred embodiment of the invention. The inhalator 1 comprises a housing enclosing a J-formed passage comprising an inlet section 3, an outlet section 4 which includes the function of a mouthpiece 2, and a bolus compartment 5 disposed between them. The outlet section comprises a dosing unit 8 which is only schematically indicated in the Figures in respect of its position; since such dosing units are known and their construction 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 the outlet section 4 in which also means (not shown) are disposed for directing the air flow towards the dose and for making the flow turbulent. The outlet section is also shown schematically only in the Figures, and may have a design and a position different from those in the Figures.

A flap 6 which can swivel by 180° around an axis C (Fig. 2) between a closed position and an open position is disposed so as to keep the passage at the transition between the inlet section 3 and the bolus compartment 5 in closed an idle state; this is the position shown in Figs. 1 , 1 a, and 5. The flap 6 and its shaft 7 are made in one piece. The ends of the shaft 7 are joumalled in bores located in the housing wall 15 (see, Figs. 5-7). At its free end the flap 6 comprises a crescent-shaped section 1 1 of a permanently magnetic material facing a correspondingly shaped section 10 of soft iron disposed on a closed- position seat face or shoulder of the valve. The positions of the soft iron material and the permanently magnetic material can be exchanged without affecting their function. The flap 6 has the form of a flat plate; it may consist of an injection moulded polymer material containing soft iron particles or permanently magnetic particles. In an injection-moulded flap 6 containing magnetic material 11 the magnetic force is evenly distributed, whereby the flap 6 can be kept in a closed position by a substantially constant magnetic force along its entire area of abutment against the seat face comprising a ferromagnetic material.

If a need for inhalation arises the user brings the mouthpiece to its mouth. By a vigorous inhalation the user sucks out the air resident in the outlet section 4 and the bolus compartment 5. If the user thereby generates a negative pressure of a predetermined size exerting a force on the flap 6 exceeding the retaining magnetic force, the flap 6 will swivel around the shaft 7. Substantially immediately upon the contact of the flap 6 with the seat face having been broken the magnetic force keeping the flap 6 in a closed position ceases to act. This allows the flap 6 to swivel very rapidly over an angle of 180° to the open position shown in Figs. 4 and 7. By a relatively large negative pressure being required to break the magnetic force keeping the flap 7 in the closed position an airflow of high velocity through the outlet portion 4 is formed during the opening phase; an intermediate position of the flap 6 is shown in Figs. 2 and 6. The pulverous agent is dispersed and carried by the air flow to the mouthpiece. 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 section 4 in form of a bolus. After turning by 180° the flap 6 is suddenly stopped by a circumferentially segmented valve seat ring comprising seat segments 12 alternating with seat passages 13 which allow the passage of air indicated by arrow 16. At the outer periphery of the valve seat ring 12,13 is disposed a grove 14 to provide for access of air to the seat passages 13. Thereby the flow of air is restricted in comparison with that prevailing under the bolus phase, that is, the phase during which the flap 6 swivels over an angle of 180°. Thereby the bolus of pulverous agent is transported down the airways with a velocity which is substantially lower than during the bolus phase. This reduces 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.

Another risk with the pulverous agent becoming stuck in the passage 4 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 flap 6 be again brought back to its closed position. This can be effected by, for instance, a spring element acting between the flap 6 element and the valve seat in the closed position. 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 flap 6 when the latter is brought to its open position. When the flap 6 reaches its closed position the flap 6 abuts fully sealingly against the valve seat in the closed position to prevent humidity from being adduced by air penetrating into the inhalator. Humidity may cause caking of the pulverous agent.

In the Figures "9" denotes a thread for fastening a cover (not shown) to protect the inlet and outlet of the inhalator. "17" denotes a magnetic material which is disposed at the open position valve seat 12,13 so as to repel the magnetic material 11 of the flap 6. A higher suction rate will make the flap 6 approach the open position valve seat 12,13, thereby reducing the area transverse to air flow and exerting a flow equilibration effect.

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 flap 4 only upon the aforementioned negative pressure being reached.

Claims

C l a i m s

1. A powder inhalator (1 ) for adducing a pulverous agent to a patient by a flow of air, comprising a space for storing a dose of the agent in communication with a passage (3,5,4) extending from an inlet to an outlet (2), the inhalator (1 ) further comprising a valve assembly in the passage (3,5,4) arranged to keep the passage (3,5,4) closed except on inhalation when a dose of the pulverous agent is carried through the outlet (2), the valve assembly being so arranged as to open at a given negative pressure prevailing in a portion (5,4) of the passage (3,5,4) extending from the valve assembly to the outlet, the valve assembly comprising a valve element (6) displaceable between a closed position and an open position in it restricts the flow of air in comparison with the flow prevailing in the passage (3,4,5) immediately upon opening of the passage (3,4,5).

2. The inhalator of claim 1 , wherein the valve assembly comprises means (10,11) for keeping the valve element (6) in a closed position by a force corresponding to said negative pressure level.

3. The inhalator of claim 2, of a design making the force keeping the valve element (6) in a closed position cease to act substantially immediately on the valve element (6) when the latter is displaced from its closed position.

4. The inhalator of any of claims 1 to 3, wherein the valve element (6) is swivellingly disposed around the axis of a shaft (7) for displacement between a closed position and an open position.

5. The inhalator of any of claims 1 to 4, wherein the valve element (6) comprises a substantially flat plate.

6. The inhalator of any of claims 1 to 5, wherein the valve element (6) abuts against at least one support in a closed position, said support comprising a permanently magnetic or magnetisable material (10).

7. The inhalator of any of claims 2 to 6, wherein said means (10,11 ) for keeping the valve element in a closed position comprise at least one permanently magnetic material or magnetisable material arranged for cooperation with a permanently magnetic or magnetisable material to keep the valve element (6) in a closed position.

8. The inhalator of claim 7, wherein the magnetic material comprises permanently magnetic material.

9. The inhalator of any of the preceding claims, wherein the valve assembly (6,7,10,11 ,12,13) comprises valve element retracting means arranged for retracting the valve element (6) from an open position to a closed position upon the negative pressure ceasing to act.

10. The inhalator of claim 9, wherein the valve element retracting means comprise spring means.

11. The inhalator of claim 10, comprising valve element repelling means (11 ,17) arranged to repel the valve element (6) from the open position valve seat (12,13) by a short distance during inhalation.

12. 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 (6,7, 10, 11 , 12, 13) opening at a predetermined negative pressure generated by an inhalation of the patient, the valve means (6,7,10,11 ,12,13) being arranged to be kept in an open position during the inhalation once the valve has been opened, thereby generating a predetermined first air flow rate through the valve means (6,7,10,11 ,12,13) to form an aerosol bolus comprising said 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 flow rate which is controlled by the valve means in the open position partially restricting air flow.

13. The inhalator of claim 12, wherein the first air flow rate is at least twice as high as the second air flow rate.

14. A method of administration of a pulverous agent to the lungs of a person, comprising making the person inhale through an inhalator to create a negative pressure sufficient to open a valve upstream of a single dose of a pulverous medicine disposed in the inhalator, thereby creating an air flow sufficient to form an aerosol bolus of the medicine; upon the formation of the bolus, restricting the air flow to protect medicine particles of the bolus from impinging on the airways mucosa during inhalation.

15. The method of claim 14, where the air flow velocity during bolus formation is at least twice as high as the velocity during transport of the bolus down the airways.

16. The method of claim 14 or claim 15, comprising stabilising the air flow velocity during transport of the bolus down the airways by a self-regulating valve arranged in the inhalator.