Abstract:
A metering element for an inhalation device is provided. The metering element comprises a plurality of openings being configured to receive a substance, wherein at least one of the openings has a different size than at least one other opening. Furthermore, an assembly for an inhalation device is provided. The assembly comprises a metering element with a plurality of openings and a powder channel which comprises an opening, wherein an arrangement of the openings is adapted to the shape of the powder channel such that each opening extends into the opening of the powder channel for a different amount.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    The present application is a U.S. National Phase Application pursuant to 35 U.S.C. §371 of International Application No. PCT/EP2014/056621 filed Apr. 2, 2014, which claims priority to European Patent Application No. 13162150.0 filed Apr. 3, 2013. The entire disclosure contents of these applications are herewith incorporated by reference into the present application. 
     
    
     TECHNICAL FIELD 
       [0002]    The present disclosure relates to a metering element for an inhalation device and an inhalation device comprising a metering element. 
       BACKGROUND 
       [0003]    A metering element for an inhalation device is known from document WO 2009/065707 A1. This application relates to a metering device which can be activated by the suction airflow of a user for inhaling a powdery substance which is arranged in a supply chamber. 
       SUMMARY 
       [0004]    It is an object of the present invention to provide a metering element for an inhalation device having improved properties. 
         [0005]    According to one aspect of the disclosure, a metering element for an inhalation device is provided. The metering element comprises a plurality of openings being configured to receive a substance, wherein at least one of the openings has a different size than at least one other opening. The inhalation device may be used for the inhalation of a substance. The substance may be stored in storage chamber of the device. The openings may be configured to receive a predetermined amount of the substance. Thereby, an amount of the substance which is required for one inhalation may be measured. 
         [0006]    The advantage of a metering element comprising differently sized openings is that the substance may flow out of the openings during an inhalation with a different flow rate. The flow rate correlates to the particles of the substance which flow out of an opening in a particular time. Furthermore, the substance may have a different adherence in the different sized openings. Thereby, the substance may be delivered to a powder channel of the inhalation device from the different openings time delayed. Thereby, a distribution of the substance in the powder channel may be improved. Thereby, the substance which is inhaled by a user may comprise a sufficient fine particle fraction. Thereby the fine particle dose which is inhaled during one inhalation is increased. Thereby, the effect of the inhalation may be improved. 
         [0007]    According to one embodiment each opening may have a size different from the other openings. According to an alternative embodiment, each opening may have the same size as the other openings. The metering element may comprise at least three openings. For example the metering element comprises three openings. 
         [0008]    According to one embodiment, at least one of the openings may have the form of an ellipse. Preferably, all openings have the form of an ellipse. In an alternative embodiment, at least one of the openings may have the form of a circle. The form of the openings may have an influence of the adherence of the substance in the openings. 
         [0009]    According to one embodiment, the openings are arranged in a pattern of a circle. Alternatively, the openings may be arranged in a pattern of a circle, a rectangle or a rhomb. In particular, the openings may be arranged at an end of the powder channel of the inhalation device and partially extend into the powder channel when the device is ready for an inhalation. At the end of the powder channel, the powder channel may comprise an opening such that the substance may flow into the powder channel from the openings of the metering element. In particular, the metering element may abut or be arranged next to an end of the powder channel. 
         [0010]    According to one embodiment, the distance of an opening to its adjacent openings is the same. In particular, each opening has the same distance to its adjacent openings. The distance of an opening to its adjacent openings may be small, for example 1 mm. In particular, the distance of an opening to its adjacent openings may be as small as possible due to the producibility of the metering element, in particular the openings. 
         [0011]    According to one embodiment, the metering element is configured to be moved in a moving direction. For this purpose, the metering element may comprise a knob. The knob may be clasped by another element of the device. By means of the knob, a movement may be transferred to the metering element from another element of the device. The metering element may be configured as a rod. Preferably, the metering element is configured as a flat bar. The metering element may have a rectangular cross-section. Alternatively, the metering element may have a circular cross-section. 
         [0012]    The metering element may be configured to move axially in a moving direction. The moving direction may be a direction along the longitudinal axis of the metering element. In an alternative embodiment, the moving direction may be a direction tilted with respect to the longitudinal axis, in particular perpendicular to the longitudinal axis of the metering element. Furthermore, the metering element may rotate with respect to its longitudinal axis. For delivering a dose of substance, the metering element may be moved along the longitudinal axis towards a dispensing end of the device. After use, the metering element may be moved away from the dispensing end of the device. 
         [0013]    Preferably, the metering element is configured to measure a sub-quantity of a substance from a total quantity of substance. In particular, the metering element may receive a sub-quantity of substance via the opening. The substance may be a powder. The substance may be a medicament. 
         [0014]    In a preferred embodiment, the metering element comprises a plurality of metering chambers. The metering chambers may be cavities provided in the metering element. The cavities may be conical. Thereby, the substance may easily run into the metering chamber. Preferably, the openings lead into the metering chambers. The metering chambers may be configured to admeasure a sub-quantity of the substance. 
         [0015]    Preferably, the openings are arranged eccentrically on the metering element with respect to the longitudinal axis. Thereby, the metering chambers may act as shovels gathering substance when the metering element is rotated. On rotation and axial movement of the metering element the openings, respectively the metering chambers, move through an accumulation of substance helicoidally. In particular, the openings may be moved along a screw curve when the metering element performs a combined axial and rotational movement. Thereby, an adequate filling of the metering chambers with substance may be achieved on rotation and axial movement of the metering element. 
         [0016]    According to one aspect of the invention, an assembly for an inhalation device is provided. The assembly comprises a metering element which comprises a plurality of openings. Furthermore, the assembly comprises a powder channel. Via the powder channel, substance may be dispensed to a user by means of an airflow. The airflow may be generated when a user inhales. The arrangement of the openings is adapted to the shape of the powder channel such that each opening extends into the opening of the powder channel for a different amount. In particular, the openings may be arranged around the powder channel. The metering element may be configured as previously described. 
         [0017]    During an inhalation, the sub-quantity of substance may flow through the powder channel. Preferably, the flow profile of the substance in the powder channel is influenced by the shape and the arrangement of the openings. The flow profile may describe the velocity and the path of the particles of the substance. Furthermore, the flow profile of the substance in the powder channel may be influenced by the shape of the metering chamber. Preferably, the substance comprises a fine particle fraction. Preferably, the flow profile has an influence on the composition of the fine particle fraction of the substance. 
         [0018]    The advantage of an assembly for an inhalation device wherein each opening extends into the powder channel for a different amount is that a distribution of a substance in the powder channel may be improved. In particular, the substance may be dispensed into the powder channel with a different flow rate from each opening. Thereby, a high amount of the substance which is dispensed into the powder channel during one inhalation may strive along an interior wall of the powder channel. Thereby, a deaggregation of the substance may be achieved. Thereby, the substance which is inhaled by a user may comprise a sufficient fine particle fraction. In particular, the separation of a micronized portion of the substance from a carrier material is achieved. Thereby, the medical effect of an inhalation may be improved. 
         [0019]    According to one embodiment, the assembly may comprise a storage chamber. The storage chamber is configured to contain a quantity of substance. In particular, the storage chamber may be configured to contain an amount of substance which corresponds to a plurality of sub-quantities of substance. 
         [0020]    The metering element is configured to transport a sub-quantity of substance out of the storage chamber. In particular, the metering element may be configured to transport a sub-quantity of substance out of the storage chamber via the metering chamber. In particular the metering element may be configured to transport a sub-quantity of substance into the powder channel. 
         [0021]    Preferably, the metering element is configured to rotate and axially move with respect to the storage chamber. The metering element may axially move from a first position inside the storage chamber to a second position outside the storage chamber. The first position may be a proximal position of the metering element furthest away from the dispensing end of the device. In the first position the metering element is at least partially positioned in the storage chamber. In particular, at least the metering chamber is fully dipped in the storage chamber. The second position may be a distal position of the metering element nearest to the dispensing end of the device. In the second position, the metering element is positioned outside of the storage chamber. In particular, the metering chamber is positioned outside of the storage chamber. 
         [0022]    Preferably, the metering element gathers a sub-quantity of substance from the storage chamber on rotation, in particular on rotation and axial movement. The metering element may gather a sub-quantity of substance when it is in the storage chamber. Preferably, the metering element transports a sub-quantity of substance out of the storage chamber on axial movement. 
         [0023]    According to one embodiment, the openings may be partially covered when the metering element is in a position furthest away from the storage chamber, in particular in its second position. The openings may be partially covered by a wall of the powder channel or by another component of the device. Thereby, an intake pressure which has to be built up by a suction air flow of a user needs to be sufficient to draw the substance through the opening. In particular, the more an opening is covered, the higher the intake pressure needs to be in order to draw the substance through the opening. 
         [0024]    According to one embodiment, each opening comprises a size different from the other openings. The area of an opening which is covered may be dependent on the size of the opening. In particular, the larger an opening, the larger is the area of the opening which is covered. In particular, the area which is covered may be different for each opening. According to a further embodiment, each opening comprises the same size. In such an embodiment, a different area of each opening is covered independently from the size of the opening. 
         [0025]    According to one embodiment, the larger an opening is, the more it extends into the powder channel. In particular for a metering element with different sized openings, the largest opening extends into the powder channel most. During an inhalation, the substance may be drawn from the opening which extends most into the powder channel first. The substance may be drawn from the opening which extends least into the powder channel at last. Thereby, a disposal of the substance from the different openings into the powder channel may happen time-delayed. According to one embodiment, the disposal of the substance from the different openings may happen one after another and not simultaneously. Thereby, the distribution of the substance in the powder channel may be improved. 
         [0026]    According to one embodiment, the disposal of the substance from the different openings into the powder channel may happen with a different flow rate. In particular, the less an opening extends into the powder channel, the smaller is the flow rate with which the substance flows into the powder channel. 
         [0027]    According to a further aspect of the disclosure, an inhalation device comprising the above disclosed assembly is provided. 
         [0028]    The term “substance”, as used herein may mean a pharmaceutical formulation containing at least one pharmaceutically active compound, for example for the treatment of obstructive airway or lung diseases such as asthma or chronic obstructive pulmonary disease (COPD), local respiratory tract oedema, inflammation, viral, bacterial, mycotic or other infection, allergies, diabetes mellitus. 
         [0029]    The active pharmaceutical compound is preferably selected from the group consisting of active pharmaceutical compounds suitable for inhalation, preferably antiallergenic, antihistamine, anti-inflammatory, antitussive agents, bronchodilators, anticholinergic drugs, and combinations thereof. 
         [0030]    The active pharmaceutical compound may for example be chosen from: 
         [0031]    an insulin such as human insulin, e.g. a recombinant human insulin, or a human insulin analogue or derivative, a glucagon-like peptide (GLP-1) or an analogue or derivative thereof, or exendin-3 or exendin-4 or an analogue or derivative of exendin-3 or exendin-4; 
         [0032]    an adrenergic agent such as a short acting β2-agonists (e.g. Salbutamol, Albuterol, Levosalbutamol, Fenoterol, Terbutaline, Pirbuterol, Procaterol, Bitolterol, Rimiterol, Carbuterol, Tulobuterol, Reproterol), a long acting β2-agonist (LABA, e.g. Arformoterol, Bambuterol, Clenbuterol, Formoterol, Salmeterol), an ultra LABA (e.g. Indacaterol) or another adrenergic agent (e.g. Epinephrine, Hexoprenaline, Isoprenaline (Isoproterenol), Orciprenaline (Metaproterenol)); 
         [0033]    a glucocorticoid (e.g. Beclometasone, Budesonide, Ciclesonide, Fluticasone, Mometasone, Flunisolide, Betamethasone, Triamcinolone); 
         [0034]    an anticholinergic agent or muscarinic antagonist (e.g. Ipratropium bromide, Oxitropium bromide, Tiotropium bromide); 
         [0035]    a mast cell stabilizer (e.g. Cromoglicate, Nedocromil); 
         [0036]    a xanthine derivative (e.g. Doxofylline, Enprofylline, Theobromine, Theophylline, Aminophylline, Choline theophyllinate); 
         [0037]    an eicosanoid inhibitor, such as a leukotriene antagonist (e.g. Montelukast, Pranlukast, Zafirlukast), a lipoxygenase inhibitor (e.g. Zileuton) or a thromboxane receptor antagonist (e.g. Ramatroban, Seratrodast); 
         [0038]    a phosphodiesterase type-4 inhibitor (e.g. Roflumilast); an antihistamine (e.g. Loratadine, Desloratadine, Cetirizen, Levocetirizine, Fexofenadine); 
         [0039]    an allergen immunotherapy (e.g. Omalizumab); 
         [0040]    a mucolytic (e.g. Carbocisteine, Erdosteine, Mecysteine); 
         [0041]    an antibiotic or antimycotic; 
         [0042]    or a combination of any two, three or more of the above-mentioned compound classes or compounds (e.g. Budesonide/Formoterol, Fluticasone/Salmeterol, Ipratropium bromide/Salbutamol, Mometasone/Formoterol); 
         [0043]    or a pharmaceutically acceptable salt or solvate or esters of any of the above named compounds. 
         [0044]    Pharmaceutically acceptable salts are for example acid addition salts and basic salts. Acid addition salts are e.g. a chloride, bromide, iodide, nitrate, carbonate, sulfate, methylsulfate, phosphate, acetate, benzoate, benzenesulfonate, fumarate, malonate, tartrate, succinate, citrate, lactate, gluconate, glutamate, edetate, mesylate, pamoate, pantothenate or a hydroxy-naphthoate salt. Basic salts are for example salts having a cation selected from alkali or alkaline, e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), wherein R1 to R4 independently of each other mean: hydrogen, an optionally substituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenyl group, an optionally substituted C6-C10-aryl group, or an optionally substituted C6-C10-heteroaryl group. Further examples of pharmaceutically acceptable salts are described in “Remington&#39;s Pharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), Mark Publishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia of Pharmaceutical Technology. Pharmaceutically acceptable ester may for example be acetates, propionates, phosphates, succinates or etabonates. 
         [0045]    Pharmaceutically acceptable solvates are for example hydrates. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0046]    Further features and refinements become apparent from the following description of the exemplary embodiments in connection with the figures. 
           [0047]      FIG. 1  schematically shows a sectional view of an inhalation device, 
           [0048]      FIG. 2  shows a metering element, 
           [0049]      FIG. 3  shows a section of the metering element of  FIG. 2 . 
       
    
    
     DETAILED DESCRIPTION 
       [0050]      FIG. 1  shows a sectional view of an inhalation device  1 . The inhalation device  1  is configured to be activated by a suction airflow generated by a user. The inhalation device  1  comprises a housing  3 . Furthermore, the device  1  comprises an outer cylinder  4 . The outer cylinder  4  is secured against axial movement with respect to the housing  3 . The outer cylinder  4  is rotatable with respect to the housing  3 . 
         [0051]    Furthermore, the inhalation device  1  comprises a mouthpiece  6 . Via the mouthpiece  6 , air is sucked into the inhalation device  1 . The inhalation device  1  further comprises a cap  7 . The cap  7  may be configured as a screw cap. The cap  7  is used for covering the mouthpiece  6 . The cap  7  may be rotatable about a main longitudinal axis x of the inhalation device  1  in a first direction with respect to the housing for screwing the cap  7  onto the device  1  and in a second direction with respect to the housing  3  for unscrewing the cap  7  from the device  1 . The outer cylinder  4  is rotationally connected to the cap  7 . In particular, the outer cylinder  4  follows a rotation of the cap  7  with respect to the housing  3 . For a detailed description of the components of the inhalation device  1  and their mechanical cooperation it is referred to document WO 2009/065707 A1, the entire content of which is explicitly incorporated by reference into the present description, in particular as far as the operation of the device  1  is concerned. 
         [0052]    The device  1  further comprises a storage chamber  15 . The storage chamber  15  holds at least one dose of a substance  2 . In particular, the storage chamber  15  may hold a plurality of doses of a substance  2 . The substance  2  may comprise a drug. The substance  2  may comprise a powder. 
         [0053]    The storage chamber  15  is terminated by a chamber sealing  24 . In particular, the side of the storage chamber  15  which is faced towards the mouthpiece is terminated by the chamber sealing  24 . The device  1  further comprises a rotary part  25 . The rotary part  25  is connected in a rotationally fixed manner to the outer cylinder  4 . Accordingly, the rotary part  25  follows a rotation of the outer cylinder and, hence, of the cap  7  about the main longitudinal axis x with respect to the storage chamber  15 . 
         [0054]    The chamber ceiling  24  comprises a central through opening. A cylindrical portion  25 A of the rotary part  25  passes through the central through opening of the chamber ceiling  24 . 
         [0055]    The inhalation device  1  further comprises a metering element  33 . The metering element  33  may comprise a metering rod. The metering element  33  may have a circular or a non-circular cross-section. For example, the metering element  33  may have a rectangular cross-section. 
         [0056]    The metering element  33  comprises a longitudinal axis mx. The longitudinal axis mx of the metering element  33  is parallel to the main longitudinal axis x of the device  1 . In particular, the longitudinal axis mx coincides with the main longitudinal axis x of the device  1 . The metering element  33  is axially and rotationally movable with respect to the storage chamber  15 . When the cap  7  is demounted from the device  1 , i.e. during an operation of the device  1 , the metering element  33  is moved in a distal direction  18 . The distal direction  18  is a direction towards a dispensing end of the device. When the cap  7  is remounted onto the device  1 , i.e. after an operation was completed, the metering element  33  is moved in a proximal direction  19 . The proximal direction  19  is a direction away from the dispensing end of the device. The metering element  33  is rotationally connected to the rotary part  25  by mechanical cooperation with the rotary part  25 . Accordingly, the metering element  33  follows rotational movement of the cap  7  and, hence, of the rotary part  25  about the main longitudinal axis x when the cap  7  is mounted onto the device  1  or demounted from the device  1 . 
         [0057]    The metering element  33  comprises at least one metering chamber  40 . The metering chamber  40  is located near a proximal end of the metering element  33 . The proximal end of the metering element  33  is the end, which his located in the storage chamber  15  when the cap  7  is mounted on the device. The metering element  33  is configured for moving the metering chamber  40  from a first position, wherein the metering chamber  40  is located inside the storage chamber  15 , to a second position, wherein the metering  40  is located outside of the storage chamber  15 . The metering chamber  40  is configured for measuring and accommodating a sub-quantity  14  of the substance  2  which is to be dispensed during an inhalation action performed by a user. In particular, a sub-quantity  14  of the substance  2  may be transported from the storage chamber  15  to a powder channel  16  via the metering chamber  40 . In order to collect a sub-quantity  14  of the substance  2 , each metering chamber  40  comprises an opening  10 . As can be seen in  FIGS. 2 and 3 , the openings  10  are arranged eccentric with respect to the axis mx on the metering element  33 , in order to achieve an adequate filling of the metering chambers  40  with substance  2 . In particular, the metering chambers  40  helicoidally move through the storage chamber  15 , thereby gathering a sub-quantity  14  of substance  2 . 
         [0058]    For a detailed description of the operation of the metering element  33 , it is referred to document WO 2009/065707 A1. 
         [0059]      FIG. 2  shows a metering element  33  which is configured for use in an inhalation device  1  as described with reference to  FIG. 1 . The metering element  33  comprises three openings  10 . The openings  10  have a different size. 
         [0060]    Furthermore, the metering element  33  comprises a knob  11 . The knob  11  serves as a holding element. In particular, the metering element  33  is mounted in the device by means of the knob  11 . Furthermore, the metering element  33  may be moved by means of the knob  11 . The knob  11  is clasped by another element of the device, as shown in  FIG. 1 . 
         [0061]      FIG. 3  shows a detailed view of the part of the metering element  33  comprising the openings  10 . Furthermore, the position of the powder channel  16  relative to the metering element  33  is indicated. In particular, the profile of a wall  17  of the powder channel  16  is shown. In  FIG. 3 , the metering element  33  is shown in a relative position with respect to the powder channel  16  when the metering element  33  has been moved out of the storage chamber  15 . In particular, a sub-quantity of substance  2  may be delivered to the powder channel  16  when the metering element  33  is in the position shown in  FIG. 3 . 
         [0062]    The openings  10  of the metering element each have the form of an ellipse. The openings  10  are arranged along the circular opening  9  of the powder channel  16 . In particular, the openings  10  extend into the powder channel  16 . Furthermore, the openings  10  are partially covered, for example by the wall  17  of the powder channel  16  or by another component of the device. 
         [0063]    Each opening  10  of the metering element extends into the opening  9  of the powder channel  16  for a different amount. This amount may depend on the size of each respective opening  10 . In particular, the larger the size of an opening  10 , the more the opening  10  extends into the opening  9  of the powder channel  16 . 
         [0064]    In each metering chamber  40 , a different pressure ratio is developed during an inhalation. Thereby, the substance  2  flows into the powder channel  16  against a different flow resistance when a user inhales. In particular, the opening  10  which extends least into the opening  9  of the powder channel  16  generates the highest flow resistance. The opening  10  which extends least into the opening  9  of the powder channel  16  is the smallest opening  10 . Furthermore, the smaller the metering chamber  40 , the more the substance  2  adheres to an interior wall of the metering chamber  40 . 
         [0065]    The different flow resistance effects that the substance  2  is delivered to the powder channel  16  from each opening  10  time-delayed. When a user inhales, the substance  2  from the opening  10  which extends into the opening  9  of the powder channel  16  for the greatest amount, i. e. the largest opening  10 , flows into the powder channel  16  first, and the substance  2  from the opening  10  which extends into the opening  9  of the powder channel  16  for the smallest amount, i. e. the smallest opening  10 , flows into the powder channel  16  at last. Thereby, a good distribution of the substance  2  in the powder channel  16  is achieved. Since the substance  2  is delivered from the openings  10  into the powder channel  16  consecutively instead of simultaneously, a large amount of the substance  2  may strive along an interior wall of the powder channel  16 . Thereby, the substance  2  may be deaggregated. Thereby, the substance  2  which is inhaled by a user may comprise a sufficient fine particle fraction. In particular, the separation of the micronized portion of the substance from a carrier material is achieved.