Inhaler

[0001] This invention relates to an inhaler for delivering a medicament to a patient, and in particular a metered dose inhaler.

Background of the invention [0002] Inhalers are known for delivering a drug to a patient by inhalation. Such devices contain metered dose inhalers (of both pressure and dry powder type). Metered dose inhalers typically have a reservoir containing the drug and a housing with an actuator comprising the drug outlet in the form of a mouthpiece or a nasal cap.

[0003] The drug-containing reservoir may be a pressure container containing a mixture of active drug and propellant. Such containers are usually made of a deep-drawn aluminum canopy having a crimped lid that holds the dispense valve assembly. The dispense valve assembly is equipped with a protruding valve stem, which during use is inserted as a close-fitting button into a so-called stem block in the housing with the actuator.

[0004] Metered dose inhalers may be both of the manually operated type and of the breath activated type. For the manually operated type, the patient administers the drug himself by manually pushing the closed end of the container into the housing with the actuator, causing the container to move relative to its valve stem (which is secured in the stem block in the housing with the actuator). This offset is sufficient to actuate the container metering valve assembly, which causes the pressurized contents of the dispensing chamber to be blown out of the stem, through the stem block and its outlet nozzle and through the opening, and causes the drug to leave the mouthpiece or nasal cap as a mist aerosol. Simultaneously with this action, the patient inhales through the nasal cap or mouthpiece, entraining the aerosol mist in the stream of inhaled air. Then the patient releases the pressure on the container, which under the action of the internal valve spring moves upwards in relation to the valve stem, returning to its resting position.

[0005] A more recent development is the so-called metered dose inhaler that serves to automatically move the container relative to its valve stem and releases the contents of the container dispensing chamber in response to the patient's inspiration. The overall purpose of such inhalers is to alleviate the difficulty of coordinating the actuation of the dispense valve assembly with the patient's inspiration and to ensure that the maximum amount of drug is drawn into the patient's lungs. A metered dose inhaler is disclosed in WO 01/93933 A2.

[0006] A housing with an actuator is generally considered an integral part of the drug delivery system, since the housing design can have a large impact on the form of drug produced for inhalation by the patient. The housing with the metered dose inhaler device usually includes an air inlet device for creating an air flow through the housing with the actuator to which the drug is released.

[0007] Furthermore, in breath actuated inhalers, the air flow through the housing with the actuator typically activates or at least acts in some way on the breath actuated mechanism. Accordingly, the housing with actuator in such inhalers includes air intakes designed to allow air to flow through the housing. However, such air intakes have the problem that they can be covered or clogged by the patient's hand or finger during use, thereby preventing or affecting the airflow through the housing with the actuator, which causes the breath actuated mechanism to malfunction. This problem is often aggravated by the fact that the air intakes are located on the housing with the actuator in places that are convenient for handling the inhaler during use by the patient.

[0008] US 2008/0196718 A1 and US 6994083 B2 disclose drug dispensers having recessed air inlets.

[0009] Thus, there is a need in the art to provide improved airflow settings for inhalers that are less susceptible to clogging or blocking by the patient during use, while at the same time enabling adequate and convenient handling by the patient.

[0010] Attention should also be paid to United States Industrial Design No. 395 147, which discloses a decorative pattern for an inhaler.

Summary of the Invention [0011] The invention provides a metered dose inhaler for delivering a medicament to a patient in accordance with claim 1. Optional features of the invention are defined in the dependent claims.

[0012] The inventors have found that the placement of a plurality of elongated slots containing respective differing apertures, each extending in two different planes, minimizes the risk of the air intake device being blocked. By differing holes is meant that the hole in each slot is defined at least partially by surfaces that are specific to that hole.

[0013] Therefore, embodiments of the invention may prevent the patient from blocking the air intake device during use, in particular by the patient's finger or thumb, each of which contains soft tissue and may adapt to different protrusions on the surface. By providing void spaces between the patient and the gaps when the patient covers the air intake device, substantially air flow can be maintained, allowing air to flow through the air intake device despite the air intake device being covered by the patient.

[0014] The invention can be applied to known inhalers only with minimal structural changes, thus limiting possible patient embarrassment and avoiding the high tool costs that would be associated with more significant structural changes.

[0015] The slots in the air intake device may be parallel to each other. In this way, it may be possible to maximize the air flow through the air intake device with a precisely defined cross-sectional area. Convex, longitudinal structures in the form of fins may be placed between adjacent slots to define different holes in the slots.

[0016] The slots may have a length in the range from 2 mm to 20 mm, preferably in the range from 4 mm to 12 mm. The slots may have a width in the range of 0.5 mm to 2 mm, preferably about 1 mm. The distance between adjacent slots can be the same as the width of the slots. The structures of convex surfaces sandwiched between adjacent slots may have a height in the range from 0.5 mm to 5 mm, preferably from 1 mm to 3 mm.

[0017] In some embodiments, each slot actually includes a different depression in the outer surface of the housing, which depression defines an opening in the slot. The surface area of ​​the opening in each slot (in the outer surface of the housing) may be greater than the surface area of ​​the slot in the interior surface of the housing, for example a recess may surround the slot. However, it is generally preferred that at least one dimension of the cavity is the same or similar to the corresponding dimension of the gap, in order to minimize the risk of blockage of the air intake device.

[0018] As mentioned above, it is an essential feature of the invention that the hole in each slot extends in two different planes, i.e. the hole defines a certain curvature or edge between the oblique planes. The hole in each slot extends in different planes defining an angle of at least 45 degrees, preferably at least 60 degrees, and more preferably at least 80 degrees.

[0019] The housing comprises an elongated body, which body may be uniform or multi-part. The air intake device is located at the end of the elongated body, which can be opposite the end at which the drug delivery port is located. In this case, the air intake device may comprise a pair of meshes in longitudinal slots arranged on opposite sides of the end face of the longitudinal body, with convex, longitudinal surface structures sandwiched between the meshes.

[0020] The inhaler may be a breath actuated, metered dose inhaler. The housing may be adapted to receive a pressure container containing the drug.

Brief Description of the Drawings [0021] An embodiment of the invention will now be described by way of example only, with reference to the accompanying diagrams in which:

Figure 1 shows an inhaler comprising an air intake device according to the state of the art document WO 01/93933 A2;

Figure 2 is an enlarged view of an inhaler comprising an air intake device according to an embodiment of the invention; and

Figure 3 is a side view of the inhaler shown in Figure 2.

Detailed description [0022] The invention provides an inhaler, for example a breath actuated metered dose inhaler, for delivering a medicament to a patient. This inhaler includes a drug storage housing and includes an air inlet device and a drug delivery port that together define the air flow path in which the drug is suspended. The air intake device includes a series of longitudinal slots formed in the housing, the long walls of the adjacent slots face each other. Each slot has a corresponding, different hole in the outer surface of the housing. The hole in each slot extends in two different planes in such a way that if at least part of the hole is covered in one of two different planes during inhalation by the patient, an empty space is created between the cover and the gap to provide airflow through empty space to at least one slot.

[0023] Referring to Figure 1, there is shown a breath actuated metered dose inhaler 10 including an air intake device 12 in accordance with prior art document WO 01/93933 A2. A detailed explanation of the principle of operation of the inhaler 10 is not important for understanding the invention, but a brief explanation will be provided by means of basic information.

[0024] The inhaler 10 comprises a main body 14 and a plug 16, which together form an elongated housing with an actuator. The main body 14, which is substantially cylindrical in cross section, is provided with a transversely extending mouthpiece 18 at one end and at the other is adapted to receive a portion of the cylindrical pressure container containing the drug. A stem block (not shown) is disposed in the main body 14 to accommodate the container valve stem and includes an outlet nozzle and a connection opening to the mouthpiece 18.

[0025] The end cap 16, which is also generally cylindrical in cross section, is equipped with an air intake device 12 at one end and at the other end is adapted to receive the remainder of the container. The main body 14 and end cap 16 are connected to each other by a threaded connection. The components of the breath actuated mechanism (not shown) are contained in both the main body 14 and the end cap 16.

[0026] The breath actuating mechanism and the container contained in the housing 14,16 provide one or more air paths so that air can pass through the air inlet device 12 to the mouthpiece 18 through the interior of the housing 14,16.

[0027] The mouthpiece 18 is equipped with a dust cap 20 revolving around an axis 22 between a first (closed) position (as shown in Figure 1) and a second (open) position. In use, the patient rotates the dust cap 20 to its open position and inserts the protruding mouthpiece 18 into his mouth. When the patient inhales through the mouthpiece 18, the pressure difference across the housing 14.16 causes the breath actuated mechanism to automatically move relative to its valve stem. The drug contained in the dispensing chamber of the container is therefore released in response to the patient's inspiration.

[0028] In a patient during inspiration, air flows from the air intake device 12 through the housing 14, 16 to the mouthpiece 18 and thus to the patient. The drug released from the dispensing chamber of the container is entrained in this air flow.

[0029] After inhalation of the drug dose by the patient, the dust cap 22 is rotated to its closed position and this causes the breath actuated mechanism and the aerosol container to be moved to the resting position, ready for the next use.

[0030] The air intake device 12 of the inhaler 10 shown in Figure 1 comprises a plurality of elongated slots 24 formed at the end of the end face of the plug 16. The slots 24 are arranged in a pair of meshes positioned on opposite sides of the end face. Although the amount of three-dimensionality 26 placed between the rows is limited, the holes in the adjacent slots 24 in each of the rows define a flat surface. Therefore, when using the inhaler, there is the problem that the gaps 24 can be blocked by the patient's finger or thumb, which can lead to a malfunction of the breath actuated mechanism and / or incomplete or ineffective delivery of the drug to the patient.

[0031] Referring to Figures 2 and 3, there is shown an enlarged view of an inhaler 100 comprising an air intake device 102, in accordance with an embodiment of the invention. With the exception of its air inlet device 102, the inhaler 100 according to the invention has the same structure and use as the known inhaler 10 shown in Figure 1. A detailed description of the individual components of the inhaler 100, other than the end cap containing the air inlet device 102, will therefore omitted. Similarly, a detailed description of the use of the inhaler 100 will also be omitted.

[0032] The air intake device 102 of the inhaler 100 includes a plurality of parallel, elongated slots 104 having an approximately rectangular shape. The slots 104 are formed on the end face of the plug 106. The slots 104 are arranged in two different rows disposed on opposite sides of the face, each row having five slots 104 whose long edges face each other. The short slit walls 104 in one row face the short edges of the slots 104 in other rows and are separated by a pair of longitudinal protrusions 108 on the surface that extend in a direction perpendicular to the length direction of the slots 104.

[0033] Each of the slots 104 is effectively recessed in the surface of the plug 106 and the recess defines an opening in the slot 104. The recesses are defined by raised, longitudinal protrusions on the surface in the shape of embossed ribs 110 sandwiched between the long walls of adjacent slots 104. Each depression is open at one end, with a corresponding end in each rib 110 which is chamfered. As such, the opening in each slot 104 extends in two substantially perpendicular planes: a horizontal plane corresponding to the "upper" portion of the opening and a vertical plane corresponding to the "lateral" portion of the opening.

[0034] The slots 104 have a length that varies from 5 mm to 7 mm and a width of 1 mm. The gap between the slots 104 is 1.2 mm, and the longitudinal ribs 104 filling this space have a height of 2.5 mm.

[0035] When using the inhaler 100, if the patient covers at least some of the holes in the slots 104 in one of two different planes, for example with his finger or thumb, then spaces are created between the patient and the slots 104 to provide an airflow path through voids to the slots 104, thereby preventing the slots 104 from being clogged or blocked by the patient.

[0036] In other words, if the air intake device 102 is covered by a surface extending in a horizontal plane that prevents vertical air flow (as shown by the arrows marked "V" in Figures 2 and 3) into the slots 104, for example, the configuration the air intake device 102 is such that the holes in the slots 104 extend at least partially in the vertical plane, allowing horizontal airflow (as shown by the arrows designated "H" in Figures 2 and 3) into the slots 104. Conversely, if the air intake device 102 is covered by a surface extending in a vertical plane, which prevents horizontal air flow (as shown by the arrows marked "H") to the slots 104, then the configuration of the air intake device 102 is such that the holes in the the recesses 24 extend in a horizontal plane, allowing vertical air flow (as shown by the arrows marked "V") into the slots 104.

[0037] With particular reference to Figure 3, it can be seen that the longitudinal ribs 110 that define the holes in the slots 104 protrude from the surrounding surface 112 of the plug 106. Thus, the longitudinal ribs 110 provide a void space that can be held between a finger or thumb patient and slots 104.

[0038] A specific embodiment has been described herein for illustrative purpose. Various modifications will be understood by those skilled in the art and may be made without departing from the scope of the invention.

[0039] For example, although the form described above is used as a breath actuated metered dose inhaler, it should be understood that alternative forms may generally include an inhaler for delivering a drug to a patient by inhalation, where it is desirable to limit or prevent the patient from blocking air inlets. . Such blocking prevention may be desirable in, for example, dry powder inhalers in which an air source is needed for effective atomization of the drug.

[0040] In the form described above, the air inlet device is located at the end of the end face of the plug. In alternative embodiments, the air inlet device may be located elsewhere, for example at the end of the main body face adjacent the mouthpiece.

[0041] The components of the inhaler of the invention will typically be molded plastic materials. Such elements may conveniently contain the surface features of the invention:

[0042] In some embodiments, the inhaler comprises a pressurized container containing a drug containing the drug and a propellant.

[0043] Typically, the drug is selected from the group consisting of anti-inflammatory agents, anti-cholinergic agents, β2 adrenoreceptor agonists, anti-infectious agents, antihistamines and combinations thereof.

[0044] Suitable anti-inflammatory agents include corticosteroids and NSAIDs. Suitable corticosteroids that can be used include corticosteroids for oral and inhalation administration and their prodrugs that have anti-inflammatory effects. Examples include methylprednisolone, prednisolone, dexamethasone, fluticasone propionate, 6a, 9a-difluoro-17a - [(2-furanylcarbonyl) oxy] -11-hydroxy-16-methyl-3-oxo-androsta-1,4-diene-17 acid -thiocarboxylic acid, 6a, 9a-difluoro-11-hydroxy-16a-methyl-3-oxo-17a-propionyloxyandrosta-1,4-diene-17p-thiocarboxylic acid ester, becomethasone esters (e.g. . ester, 17-propionate or ester, 17,21-dipropionate), budesonide, flunizolide, mometasone esters (e.g. ester, furoate), triamcinolone acetonide, rofleponide, ciclesonide, butixocortic propionate, RPR106541 and ST-126. Preferred corticosteroids include fluticasone propionate, 6a, 9c-difluoro-11-hydroxy-16a-methyl-17a - [(4-methyl-1,3-thiazole-5-carbonyl) oxy] -3-oxo-androsta- 1,4-diene-17,8-thiocarboxylic acid and 6a, 9a-difluoro-17a - [(2-furanylcarbonyl) oxy] -11-hydroxy-16-methyl-3-oxo-androsta-1,4- acid S-fluoromethyl ester diene-17p-thiocarboxylate, more preferably 6a, 9a-difluoro-17a - [(2-furanylcarbonyl) oxy] -11-hydroxy-16a-methyl-3-oxoandrosta-1,4-diene-17-carbothioic acid S-fluoromethyl ester.

[0045] Suitable NSAID agents include sodium cromoglycate; nedocromil sodium; phosphodiesterase (PDE) inhibitors (e.g., theophylline, PDE4 inhibitors or mixed PDE3 / PDE4 inhibitors); leukotriene antagonists; leukotriene synthesis inhibitors; iNOS inhibitors; tryptase and elastase inhibitors; beta-2 integrin antagonists and adenosine receptor agonists or antagonists (e.g., adenosine 2a agonists); cytokine antagonists (e.g., chemokine antagonists) or cytokine synthesis inhibitors.

[0046] Suitable other β2 adrenoceptor agonists include salmeterol (e.g. as xinafoate), salbutamol (e.g. as sulfate or as the free base), formoterol (e.g. as fumarate), fenoterol or terbutaline and salts thereof.

[0047] Suitable anticholinergic agents are compounds that act as muscarinic receptor antagonists, in particular those compounds that are M1 and M2 receptor antagonists. These compounds contain an alkaloid from plants of the belladonna, such as, but not limited to, atropine, scopolamine, homatropin, hyoscyamine; these compounds are usually administered as salts, being tertiary amines.

[0048] Particularly suitable anticholinergics include ipratropium (e.g. as bromide), sold under the name Atrovent, oxitropium (e.g. as bromide) and tiotropium (e.g. as bromide) (CAS-139404-48-1). Are also of interest: metantelin (CAS-53-46-3), propantelin bromide (CAS-50-34-9), anisotopin methylbromide or Valpin 50 (CAS-80-50-2), clidinium bromide (Quarzan, CAS- 3485-62-9), coprrolate (Robinul), isopropamide iodide (CAS-71-81-8), mepenzolate bromide (US Patent No. 2,918,408), tridihexetyl chloride (Pathilone, CAS-4310-35-4) and hexocyclic sulfate ( Tral, CAS-115-63-9). See also cyclopentolate hydrochloride (CAS5870-29-1), tropicamide (CAS-1508-75-4), trihexyphenidyl hydrochloride (CAS-144-116), pirenzepine (CAS-29868-97-1), telenzepine (CAS-80880- 90-9), AF-DX 116 or methoctramine and the compounds disclosed in WO 01/04118.

[0049] Suitable antihistamines (also referred to as H1 receptor antagonists) include any one or more of numerous antagonists known to inhibit H1 receptors and are safe for use in humans. They are all reversible, competitive inhibitors of the interaction of histamine with H1 receptors. Examples include ethanolamines, ethylenediamines and alkylamines. In addition, other first generation antihistamines include those characterized as piperazine and phenothiazine based compounds. Second-generation antagonists, without sedation, have similar structure-activity relationships in that they retain an ethylene (alkylamines) group in the core or mimic a tertiary amine group with piperizine or piperidine. Examples of such antagonists are as follows:

Ethanolamines: carbinoxamine maleate, clemastine fumarate, diphenylhydramine hydrochloride and dimenhydrinate.

[0050] Ethylenediamine: pyrilamine maleate, tripelenamine hydrochloride and tripelenamine citrate.

[0051] Alkylamines: chlorfeniramine and its salts, such as maleate, and acristastine.

[0052] Piperazines: hydroxyzine hydrochloride, hydroxyzine pamoate, cyclysine hydrochloride, cyclysine lactate, meclysine hydrochloride and cetirizine hydrochloride. [0053] Piperidines: astemizole, levocabastine hydrochloride, loratadine or its decarboethoxy analogue, and terfenadine and fexofenadine hydrochloride or other pharmaceutically acceptable salt.

[0054] Azelastine hydrochloride is yet another H1 receptor antagonist that can be used in combination with a PDE4 inhibitor.

[0055] Particularly useful antihistamines include metapyrylene and loratadine.

[0056] Preferably, the medicament is in a formulation comprising a propellant and preferably a solvent; other preferred ingredients include surfactants, including oleic acid. Preferred solvents include ethanol, glycerols and glycols.

[0057] Preferred propellants include hydrofluroalkanes; in particular 1,1,1,2-tetrafluoroethane (HFA134a); 1,1,1,2,3,3,3-heptafluoropropane (HFA227); or a combination of them. Preferably, the drug is suspended in the propellant. Alternatively, the drug is dissolved in the propellant. The drug may also be partly suspended and partly dissolved in the propellant.

Examples [0058] The following drug formulations were used in the inhaler:

Preparation example 1:

[0059]

Ingredient Amount / mg per ml

Beclometasone dipropionate 1.00 Ethanol 94.80

HFA 134a 1,090.20

Preparation example 2:

[0060]

Ingredient Mass / mg

Salbutamol sulfate 0.1098

HFA 134a 27.8

Ethanol 3.6