BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates to an inhaler. In particular, the present invention relates to an inhaler for horses or other large animals, with an adapter for a nostril or other respiratory orifice.

Description of Related Art

The invention further relates to inhalers which, on each actuation, dispense a defined dose or amount of a medicinal fluid held under excess pressure, for which reason these inhalers are also known as “pressurized metered-dose inhalers” (pMDI).

pMDI has a reservoir, which is filled with a medicament preparation and is kept under pressure by means of a propellant gas. The reservoir further comprises a metering valve for dispensing the medicament fluid. The metering valve is able to dispense a specified or measured amount of the medicament fluid on each activation. The fluid is dispensed by the movement of a valve element of the metering valve.

U.S. Pat. No. 5,666,948 A discloses a pMDI with a nostril adapter for a horse. During operation, the reservoir is normally used above the animal's head or with the valve directed downwards. A valve element of the valve is connected to the inhaler and the reservoir is movable relative to the inhaler or the valve element. For activation, the reservoir can be pressed downwards manually or be pulled down by means of a trigger button, thus dispensing a dose of the medicament fluid.

In conjunction with their use in large animals, such as horses, inhalers have the disadvantage of requiring a very robust, relatively large and complex construction, which is expensive to manufacture. At the same time, their use in large animals, unless the animals are physically restrained, rapidly leads to soiling by secretions or the like, which prevent longer-term use or re-use of the inhaler.

It has also been found that inhalers developed for use in human medicine are unsatisfactory for use on large animals. On the one hand, the amount delivered has to be many times greater, for example, 10 to 30 times greater, which is expensive and error-prone. On the other hand, known inhalers are awkward and are difficult to operate in rough conditions or wearing gloves or the like.

SUMMARY OF THE INVENTION

The object of the present invention is therefore to provide an inhaler, which is robust and/or ergonomic, compact and accurate in use on large animals and capable of being operated with little effort.

The above object is achieved by an inhaler as described herein.

The proposed inhaler is preferably designed for use in horses or other large animals. It comprises a reservoir for delivering a medicament preparation held under excess pressure, a discharge nozzle for forming an aerosol with the medicament preparation and a chamber for receiving and temporarily storing the aerosol, which may also be termed the spacer. The chamber further comprises, or forms, an adapter for a respiratory orifice, particularly a nostril. The adapter may also be formed separately from the chamber and/or connected to the chamber.

According to a first aspect of the present invention, which can also be implemented independently, the reservoir is secured in position, at least in the axial direction. Preferably, the reservoir is held by interlocking engagement, in particular, in the inhaler so as to prevent axial movement at least when the inhaler is in operation. The reservoir is preferably secured in position with respect to the inhaler, particularly an inhaler housing, the chamber and/or the adapter for the respiratory orifice.

In inhalers, the reservoir is normally moved relative to the inhaler in order to activate it. Instead, in the proposed inhaler, the reservoir is fixed, or not moved, during the activation of the dispensing of the medicament preparation. However, other solutions are also possible, particularly with a movable reservoir.

It has surprisingly been shown that fixing the reservoir enables actuation to be carried out more easily, cheaply, precisely and robustly, particularly when using an operating element such as an operating lever. This gives rise to advantages in terms of the handling properties of the inhaler as a whole, particularly for use on large animals such as horses.

It is also advantageous that, with the reservoir being immovable during activation, the entire mass of the reservoir does not have to be moved, which would require complex mechanics when used in conjunction with large animals and might lead to vibrations, which could interfere with application particularly to large animals. Also, fixing the reservoir makes it possible to have a closed construction, at least in the region of the bottom of the reservoir. This confers improved protection against the ingress of pathogens, particularly when used in stables or outside.

According to a second aspect of the present invention which can also be implemented independently, the discharge nozzle has a direction of discharge for the aerosol which encloses an angle or is inclined by more than 5°, preferably more than 10° or 15° and/or less than 50°, preferably less than 45° or 40°, particularly less than 35°, relative to a central axis of the reservoir or a direction of actuation for dispensing the aerosol.

The direction of discharge according to the present invention preferably is a main or primary direction of discharge, in particular of the discharge nozzle or nozzle opening(s) of the discharge nozzle. In particular, the direction of discharge corresponds to or at least essentially complies with a middle axis or center axis of a spray mist or spray cone produced while forming the aerosol. The direction of discharge according to the present invention preferably at least essentially corresponds to or complies with a (symmetry or middle) axis of nozzle openings of the discharge nozzle.

Preferably, the adapter for the respiratory orifice has a dispensing opening for dispensing the aerosol, which is laterally offset relative to the central axis of the reservoir or has a direction of dispensing which is laterally offset and/or skewed relative to the central axis of the reservoir. This has advantages with respect to anatomical shape and consequent ease of handling of the inhaler, particularly when it is used in large animals with the operator's arm stretched upwards. Thanks to the proposed direction of dispensing, depositing of aerosol on the walls of the chamber or adapter can be prevented or reduced. The proposed dispensing angle therefore permits good handling and ergonomics of the inhaler while at the same time achieving precise and efficient dosing.

The terms “discharge” and “dispensing” are preferably synonymous or interchangeable. In the following description, purely for greater clarity, the term “discharge” is always used, without loss of generality, in conjunction with the discharge nozzle or the aerosol formation and the term “dispensing” is used in conjunction with the aerosol that has already been produced.

A discharge nozzle in the sense of the present invention is preferably a nozzle, which is suitable for dispensing the medicament preparation while forming a preferably respirable aerosol. In particular, the discharge nozzle is a nozzle, which is suitable for nebulizing liquids.

According to a third aspect of the present invention, which can also be implemented independently, the reservoir comprises a dispensing valve arranged on the top in the position of use of the inhaler. The use of a reservoir in an upright position or with the dispensing valve at the top is unusual in inhalers. However, it has been found that such a configuration, particularly in inhalers for large animals, allows a substantially more compact, inexpensive and ergonomic construction, which is economical with materials, compared with the overhead operation with a valve at the bottom which is conventional in inhalers.

In particular, the upright arrangement of the reservoir leads to easier interchanging and reusing of the inhaler. The upright arrangement assists with the formation of an aerosol in the position of use at least substantially upwards, which in the proposed inhaler for use in large animals makes it possible to achieve a compact and ergonomic construction, particularly for animals with respiratory orifices which may be higher than the chest of the user or veterinary surgeon or animal handler.

Moreover, actuation using an operating lever can be achieved without complicated mechanics, thus contributing to a robust and inexpensive construction, which is economical with materials. Also, the reservoir may be insertable from below in the operating position. This confers improved protection against the ingress of dirt and pathogens even in external areas or stables when used on large animals.

Preferably, the reservoir comprises a riser tube, which is fluidically connected to the dispensing valve of the reservoir. This provides a simple and inexpensive way of dispensing the medicinal liquid with the valve at the top.

Moreover, the inhaler may comprise an actuating lever for triggering the aerosol formation. It allows a robust construction which enables the inhaler to be operated reliably even when wearing gloves or in dirty conditions. The actuating lever may be synergistically combined with the reservoir, which comprises a valve directed upwards in the operating position and/or is axially fixed. Surprisingly, it has been found that the actuating lever enables the production of an aerosol even under adverse conditions, outside or in stables, and even when operated while wearing gloves. It has also advantageously been found that with the actuating lever an upwardly directed valve can be operated particularly easily and reliably. In addition, a combination with a fixed reservoir allows a particularly robust and reliable construction with few mechanical parts, thus substantially improving reliability in rural use. The combination of fixed reservoir, valve directed upwards in the position of use, and the actuating lever for actuating the valve is therefore particularly preferred.

In another aspect, the discharge nozzle may comprise at least three, preferably at least four or five discharge openings. The discharge openings may have a cumulative outlet surface of more than 0.1 mm2, preferably more than 0.15 mm2. This has proved favorable for the rapid dispensing of respirable aerosol, particularly for an inhaler for large animals. Surprisingly, it has been found that using the proposed discharge nozzle makes the administration of the medicament preparation to large animals substantially easier, since, compared with inhalers with the otherwise conventional discharge nozzles, the number of actuation steps for a whole dose and the time taken to give the treatment can be reduced considerably.

The inhaler preferably has a holder for an insert, the insert comprising the reservoir, is axially insertable into the holder and/or has been inserted into the inhaler. As a result, the inhaler can be re-used.

The holder may be a retaining portion for at least axially retaining the reservoir or insert comprising the reservoir. In particular, the retaining portion may be a flap or latching means. In this way, it is possible to secure the reservoir even if the insert is exchangeable. The reservoir may be covered by the flap, at least at the bottom. This has proved advantageous as it prevents the ingress of dirt and interference with operation caused by dirt.

Particularly preferably, in the position of use, the reservoir is fully accommodated in the inhaler at least at its end, particularly at opposite ends. In this way, the ingress of dirt can be prevented.

The holder is preferably formed by or in a handle or gripping means. The handle or gripping means may be at least substantially cylindrical and/or elongate and/or have a diameter of more than 3 cm, preferably more than 3.5 cm and/or have a length of more than 10 cm, preferably more than 13 cm. This allows a large gripping surface for use in large animals such as horses, even when the user is wearing gloves, while at the same time producing a compact inhaler, as the holder is formed in the gripping surface and the gripping surface is formed around the holder, synergistically resulting in a saving of space and on materials.

The holder preferably comprises an orientation portion for orienting the insertion of the insert. In this way, the dispensing direction for the aerosol into the chamber can be fixed, particularly when the chamber is inclined relative to the central axis of the reservoir, the insert and/or the discharge nozzle.

The holder may alternatively or additionally comprise a release portion for releasing the dispensing of the medicament preparation by insertion of the insert. This ensures that the medicament preparation can only be dispensed when the insert has been inserted fully and correctly. This is for safety reasons, as, particularly in the case of medicaments for large animals, accidental release outside the inhaler could affect living creatures in the surrounding area.

Preferably, the orientation portion comprises the release portion or vice versa, and preferably the dispensing of the medicament preparation can be released by fully inserting the insert in the intended orientation. The orientation portion and the release portion may synergistically be the same part, thus saving on construction and materials.

According to another aspect of the present invention, the inhaler may comprise an exchangeable counter, the counter preferably being insertable into the holder. In particular, the counter may be exchanged together with the insert. However, it may also be exchanged separately. The possibility of exchanging it means that if the inhaler is used several times the correct count for the particular reservoir can always be displayed.

Aspects relating to an insert that can preferably be inserted into or used in the holder of the inhaler will be described in more detail hereinafter. However, by contrast, it is also possible for the inhaler itself to comprise individual ones or all of the components of the insert, or for individual ones or all of the components of the insert to be individually exchangeable. However, it is particularly preferable for the inhaler to be of modular construction. Therefore, the invention is hereinafter always described with an insert for or in the inhaler. It will be understood that the inhaler may also comprise the parts of the insert without them being present as an insert. Alternatively or additionally, the insert may be incorporated in the inhaler in fixed, non-exchangeable, non-insertable or non-removable manner, even though it is preferable for the insert to be insertable, removable or exchangeable.

The insert, which may also be produced independently, can be inserted into the inhaler, particularly for a horse. This insert comprises a reservoir for a medicament preparation held under excess pressure, said reservoir comprising a valve. Moreover, the insert has a nebulizer held directly on the reservoir and a discharge nozzle associated with the nebulizer and fluidically connected to the valve, for forming an aerosol with the medicament preparation.

The proposed insert can preferably be inserted into an inhaler and/or removed from an inhaler. In particular, the insert can be accommodated or received by the inhaler for use. The insert may be exchangeable, as a result of which an inhaler is suitable for repeated or universal use.

The nebulizer may also be produced independently and constitutes a particular aspect of the invention in its own right.

The nebulizer is preferably non-detachably connected or connectable to the reservoir. In particular, the nebulizer is clipped onto the reservoir or otherwise held thereon, preferably by latching. In this way a construction unit can be formed with the nebulizer and the reservoir, thus doing away with the replacement of individual parts.

The discharge nozzle is particularly preferably held and/or mounted on the reservoir by means of the nebulizer. In this way, a construction unit can be formed with the nebulizer, the reservoir and the discharge nozzle.

Preferably, the discharge nozzle is secured against removal, taking off or pulling off, by means of the nebulizer, or in the nebulizer. The discharge nozzle is thus preferably (in)separable from the insert, from the nebulizer or from the reservoir. In this way it can be ensured that replacement of the reservoir is accompanied by the replacement of the discharge nozzle.

Preferably, the nebulizer is non-detachably held on the reservoir. In particular, the nebulizer and/or the discharge nozzle forms an inseparable construction unit with the reservoir and preferably with the valve. The inseparable construction unit ensures that when the reservoir is exchanged or when the inhaler is reused the discharge nozzle is changed.

“Inseparable” or “non-detachable ” in the sense of the present invention means, in particular that, at least after assembly is complete, separation is only possible with greater effort, cannot be done without tools or manually and is possible only by damaging or destroying the item.

Particularly when used in connection with animals, the discharge nozzle may have a tendency to become clogged or otherwise blocked up with secretions or the like. The proposed insert, by providing for only total replacement or by the formation of the inseparable construction unit, advantageously makes it possible to prevent possibly unreliable, blocked or worn discharge nozzles from being re-used with a new or freshly filled reservoir. Consequently, when the inhaler is reused, reliable operation and dosing can be guaranteed.

The proposed insert ensures that the valve, particularly a metering chamber volume of the valve, corresponds to or is adapted to a concentration of active substance in the medicament preparation. In this way, correct dosing can be ensured.

The metering chamber volume is preferably more than 200 μ1, particularly preferably more than 250 μl, particularly more than 300 μl and/or less than 1000 μl, preferably less than 800 μl, particularly less than 600 or 400 μl. A metering chamber volume of 280 μl to 340 μl is most particularly preferred. It is possible to use the inhaler universally for different large animals, and at the same time, minimize of number of necessary actuation steps. In particular, only one to three actuations or a total dose of between 300 μl and 900 μl are particularly advantageous.

With the proposed insert, it can be ensured, alternatively or additionally, that the valve, particularly a metering chamber volume of the valve, corresponds to or fits the discharge nozzle.

Preferably, a dose of the medicament preparation or a metering chamber volume of the valve can be converted into an, in particular, respirable aerosol within a sufficiently short time span, preferably within a time span of less than a second, particularly less than half a second. It is therefore preferable for the discharge nozzle to be able to dispense at least one metering chamber volume per second, preferably at least twice the metering chamber volume per second.

Too small a metering chamber volume in relation to the amount discharged may lead to inaccuracies of dosing. Therefore, it is preferable if the discharge nozzle is able to dispense less than ten times the metering chamber volume per second.

With the proposed insert, an optimum ratio of metering chamber volume of the valve to the discharge speed of the discharge nozzle is obtained, leading to good reliability and metering accuracy.

With the proposed insert, it may alternatively or additionally be ensured that a discharge nozzle suited to the particular medicament preparation is used. In particular, the discharge nozzle may suit the properties of the medicament preparation, particularly its viscosity and flow properties. In this way, accurate dosing and/or a sufficiently fine aerosol can be obtained.

Overall, with the proposed insert, it can be ensured that a combination of medicament preparation, valve and discharge nozzle is always used which leads to reliable dosing and aerosol formation. The proposed insert thus ensures satisfactory cooperation of the components even when an inhaler is re-used.

The discharge nozzle can be guided by the nebulizer in axial, linear and/or rotationally connected manner. As a result of the axial or linear guiding, the valve can be reliably actuated by the discharge nozzle or by movement of the discharge nozzle. As a result of rotationally connected guiding, it can be ensured that the orientation of the discharge nozzle remains unchanged.

The discharge nozzle may be axially or linearly moveable for opening the valve or dispensing the medicament preparation. However, it is preferable if this axial mobility of the discharge nozzle is restricted at least to the direction of removal or dispensing for the medicament preparation or to a direction leading away from the reservoir, particularly by the nebulizer.

The discharge nozzle is preferably fluidically connected to the valve. It is also preferable if the discharge nozzle is mechanically connected to the valve, particularly to a valve element of the valve. In this way, axial movement of the discharge nozzle can move the valve element. The medicament preparation can be dispensed by the movement of the valve element. Thus, a preferably axial movement of the discharge nozzle can open the valve and activate the dispensing of the medicament preparation.

“Axial” in the sense of the present invention is preferably a movement or direction along or parallel to the central axis or an axis of symmetry of the reservoir or the insert or a movement or direction along or parallel to an axis of symmetry of the valve or valve element. In particular, the central axis corresponds to the axis of symmetry or vice versa. Moreover, the terms “central axis” or “axis of symmetry” preferably relate to a position of use of the insert or the valve. In particular, reference to the central axis or axis of symmetry is also possible irrespective of whether the insert has been inserted into the inhaler or the like.

Preferably, the direction of actuation is axial and/or corresponds or complies with a direction of movement or direction along or parallel to the central axis or an axis of symmetry of the reservoir or the insert or a movement or direction along or parallel to an axis of symmetry of the valve or valve element.

For dispensing the medicament preparation, it is preferable for the valve to be opened. In this way, medicament preparation is able to reach intake openings of the discharge nozzle and be dispensed through the dispensing openings. Preferably, the medicament preparation is dispensed through the discharge openings under a corresponding pressure or at a corresponding velocity or the like such that the aerosol is formed.

In a variant, different proposed inserts with, in particular, different medicament preparations can be used one after the other or alternately in the same inhaler. By using inserts with different medicament preparations, a respirable aerosol based on different medicament preparations can be produced and dispensed with the same inhaler or type of inhaler. This allows the inhaler to be used universally and produced efficiently in large production runs.

Features of the medicament preparation are preferably visible or displayed on the inhaler, for example through a window in the inhaler. This can prevent mix-ups.

Alternatively or additionally an insert may in particular be mechanically insertable into, or usable in, only one corresponding inhaler. The insert is preferably coded in the manner described, or in some other way, for a corresponding inhaler, particularly by orientation means, which will be discussed in more detail hereinafter. This, too, can prevent mix-ups.

Preferably, the orientation means corresponds to the orientation portion of the holder of the inhaler. In particular, the orientation means and the orientation portion are embodied to be complementary to one another, constitute a coding, can be inserted in one another or secure an orientation of the insert or the nebulizer with respect to the holder or the inhaler according to the lock and key principle.

The insert is preferably not designed for self-sufficient operation or cannot be used on its own as an inhaler. Preferably, the insert is protected from actuation outside an inhaler or otherwise embodied for use solely with or in an inhaler.

The insert is preferably free from adapters for respiratory orifices.

The insert is preferably configured to avoid, prevent or block the dispensing of medicament outside the inhaler.

The insert may comprise a cover, particularly a cap, which covers the discharge nozzle or prevents the medicament preparation from being dispensed outside the inhaler.

Particularly preferably, the insert comprises a blocking device, which is embodied to prevent accidental actuation, actuation in the non-inserted state of the insert and/or actuation after reaching or exceeding a given number of actuating steps.

The blocking device preferably corresponds to the release portion of the holder of the inhaler. In particular, the blocking device and the release portion are of complementary construction, they constitute a coding, can be inserted in one another or are configured so as to release a blocking arrangement of the actuation, particularly the opening of the valve, using the lock and key principle. This can prevent accidental actuation independently of the inhaler, which could have an effect on other living creatures particularly in the case of medicaments for large animals.

Alternatively or additionally, actuation can be prevented once a given number of actuation processes has been reached or exceeded. This can be done by means of the blocking device and/or the counter. The advantage of this is that actuation is prevented when the dosage might possibly be inaccurate, particularly when there is a reduction in the pressure in the reservoir or the like.

In another aspect of the present invention, the insert or the nebulizer may be configured to dispense the medicament preparation in a direction of discharge which corresponds at least substantially to a central axis of the reservoir and/or which extends diagonally with respect to the central axis of the reservoir. This has the advantage that no or very little deflection of the medicament preparation is needed and consequently a loss in pressure can be minimized.

As already mentioned in conjunction with the inhaler, it is also particularly preferred, in relation to the insert, if the direction of discharge is inclined by more than 5°, particularly more than 10° or 15° and/or less than 50°, preferably less than 45° or 40°, particularly less than 35° relative to the central axis of the reservoir or if such an angle is enclosed between the central axis and the direction of discharge. This advantageously makes it possible to prevent aerosol being deposited on the walls of a chamber for receiving and temporarily storing aerosol or on the walls of an adapter for a respiratory orifice, particularly while the aerosol can be dispensed from the chamber or through the adapter for the respiratory orifice, in laterally offset and/or skewed manner with respect to the central axis of the reservoir. The dispensing of the aerosol in laterally offset and/or skewed manner with respect to the central axis of the reservoir has advantages in terms of the anatomical shaping and consequent ease of handling of the inhaler.

The insert or the nebulizer may comprise the counter, which can be driven by the triggering of the dispensing of the medicament preparation. The counter preferably forms an inseparable construction unit with the reservoir and/or with the nebulizer and/or the dispensing nozzle and/or the valve. This ensures that an insert that has already been emptied or partially emptied can be recognized as such independently of an inhaler. The counter is preferably rotatable mounted in the nebulizer.

The insert or the nebulizer preferably comprises an, in particular, axially movable activating element, the medicament preparation being adapted to be dispensed by the movement of the activating element. The activating element is preferably embodied to move the valve element or to open the valve by some other means.

The counter may be drivable by the movement of the activating element.

The activating element may be blocked and released by the total insertion of the insert in the intended orientation.

Preferably, the activating element guides and/or moves the discharge nozzle in the nebulizer.

The activating element may be arranged between the discharge nozzle and a housing of the nebulizer held on the reservoir.

The activating element is preferably fixed to the discharge nozzle or formed by the discharge nozzle. The activating element may be held by latching on the housing. This allows a quick and easy and/or non-separable assembly. In particular, the activating element is or forms a shoulder for the axial movement of the discharge nozzle.

In one variant, the activating element is movable independently of the discharge nozzle. In this case, the discharge nozzle can be immovably held by the nebulizer and/or on the reservoir.

The insert or the nebulizer may comprise a frame or a shoulder, which is immovable with respect to the reservoir, the activating element being adjacent to the frame or the shoulder. The frame or the shoulder may surround, enclose and/or envelop the activating element. In this way, accidental triggering can be prevented.

The frame or the shoulder may be connected to the nebulizer or be formed by the nebulizer, particularly by a housing of the nebulizer, which is connected or connectable to the reservoir. However, other solutions are also possible.

A further aspect of the present invention, which can also be implemented independently, relates to a medical use of the insert, the reservoir, the nebulizer and/or the inhaler, in particular as described above.

In a further aspect, the present invention concerns the insert, the reservoir, the nebulizer and/or the inhaler for the use (in a method) for the management/treatment, preferably of airway disease, in particular in equines, preferably horses, preferably wherein the airway disease is a pulmonary disease, more preferably the airway disease is selected from the group consisting of: recurrent airway obstruction (RAO), summer pasture associated obstructive pulmonary disease (SPAOPD), and inflammatory airway disease (IAD).

The invention further concerns a method of treating an airway disease comprising administering a therapeutic effective amount of an active substance or a pharmaceutically acceptable salt thereof using said insert, reservoir, nebulizer and/or inhaler to a patient, preferably an equine patient, more preferably a horse, in need thereof. Preferably the airway disease is a pulmonary disease, more preferably the airway disease is selected from the group consisting of: recurrent airway obstruction (RAO), summer pasture associated obstructive pulmonary disease (SPAOPD), and inflammatory airway disease (IAD).

The term “equine” means of or belonging to the family Equidae, which includes the horses, asses, and zebras, preferably horses. In addition, the term “equine” encompasses also hybrids of members of the family Equidae (e.g., mules, hinnies, etc.)

The term “patient” or “subject” embraces mammals such as primates including humans. The term “patient” or “subject” as used herein relates specifically to horses, especially horses suffering from airway disease (particularly pulmonary disease), preferably from recurrent airway obstruction (RAO) also called heaves or equine COPD and/or summer pasture associated obstructive pulmonary disease (SPAOPD) also called Summer Pasture Associated Recurrent Airway Obstruction (SPARAO) and/or inflammatory airway disease (IAD), most preferably from RAO.

The term “airway disease” in horses means the following: recurrent airway obstruction (RAO) also called heaves or equine COPD, Summer Pasture Associated Obstructive Pulmonary disease (SPAOPD), inflammatory airway disease (IAD), exercise induced pulmonary hemorrhage (EIPH), infectious diseases, chronic interstitial lung disease and upper respiratory tract functional disorders.

The term “pulmonary disease” means: recurrent airway obstruction (RAO) also called heaves or equine COPD, Summer Pasture Associated Obstructive Pulmonary disease (SPAOPD), inflammatory airway disease (IAD), exercise induced pulmonary hemorrhage (EIPH), infectious diseases, chronic interstitial lung disease.

The term “recurrent airway obstruction (RAO)” in horses means the following: a chronic syndrome of mature horses with reversible airway obstruction in the stable showing periods of laboured breathing at rest during exacerbation.

The term “Summer Pasture Associated Obstructive Pulmonary disease (SPAOPD)” in horses means the following: a chronic syndrome, which shares many clinical and pathological similarities with RAO at rest on the pasture, suggesting similar pathogenesis, however, it is caused by different antigens.

The term “inflammatory airway disease (IAD)” in horses means the following: a chronic syndrome of horses showing poor performance or coughing or excess tracheal mucus without showing periods of laboured breathing at rest.

The term “effective amount” as used herein means an amount sufficient to achieve a reduction of airway disease in a horse when ciclesonide is administered at a dosage as described herein. The progress of the therapy (improvement of airway disease, particularly pulmonary disease, preferably recurrent airway obstruction (RAO) and/or Summer Pasture Associated Obstructive Pulmonary disease (SPAOPD) and/or inflammatory airway disease (IAD), most preferably RAO as described herein) can be monitored by standard airway/pulmonary diagnosis, for example, by clinical examination, airway fluid cytology, endoscopy, lung function measurement, or blood-gas analysis.

The term “pharmaceutically acceptable derivative thereof” means, but is not limited to, pharmaceutically acceptable salts, derivatives, metabolites or pro-drugs of a drug. Derivatives as used herein include, but are not limited to, any hydrate forms, solvates, isomers, enantiomers, racemates, racemic conglomerate and the like of the compound of choice. Suitable pharmaceutically acceptable salts are well known in the art and may be formed with an inorganic or organic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, acetic acid, glycolic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, mandelic acid, tartaric acid, citric acid, ascorbic acid, palmitic acid, maleic acid, hydroxymaleic acid, benzoic acid, hydroxybenzoic acid, phenylacetic acid, cinnamic acid, salicylic acid, methanesulfonic acid, benzenesulfonic acid and toluenesulfonic acid.

In a preferred aspect of the present invention, the active substance administered using the insert, the reservoir, the nebulizer and/or the inhaler of the present invention is a glucocorticoid, preferably ciclesonide and/or budesonide and/or fluticasone, most preferably ciclesonide.

The term “glucocorticoid” refers to a class of steroid hormones that bind to the glucocorticoid receptor (GR), which is present in almost every vertebrate animal cell. The name glucocorticoid (glucose +cortex +steroid) derives from its role in the regulation of the metabolism of glucose, its synthesis in the adrenal cortex, and its steroidal structure.

Glucocorticoids are part of the feedback mechanism in the immune system that turns immune activity (inflammation) down. They are therefore used in medicine to treat diseases caused by an overactive immune system, such as allergies, asthma, autoimmune diseases, and sepsis.

Preferred glucocorticoids according to the present invention are ciclesonide and/or budesonide and/or fluticasone.

The term “ciclesonide” ((11β,16α)-16,17-[[(R)-Cyclohexylmethylene]bis(oxy)]-11-hydroxy-21-(2-methyl-1-oxopropoxy)pregna-1,4-diene-3,20-dione, C32H44O7, Mr=540.7 g/mol) is well known in the art and means/describes a glucocorticoid used to treat asthma and allergic rhinitis in humans. It is marketed for application in humans under the brand name Alvesco™ for asthma and Omnaris™/Omniair™ for hay fever in the US and Canada. Ciclesonide is a prodrug. It is transformed into the active metabolite C21-C21-desisobutyrylciclesonide (=desciclesonide) via hydrolysis by intracellular esterases in the lung. Ciclesonide is a non-halogenated glucocorticoid, which predominantly exists in its form as R-Enantiomer.



As used herein the term “prodrug” refers to (i) an inactive form of a drug that exerts its effects after metabolic processes within the body converting it to a usable or active form, or (ii) a substance that gives rise to a pharmacologically active metabolite, although not itself active (i.e. an inactive precursor).

The terms “prodrug” or “prodrug derivative” mean a covalently-bonded derivative, carrier or precursor of the parent compound or active drug substance which undergoes at least some biotransformation prior to exhibiting its pharmacological effect(s). Such prodrugs either have metabolically cleavable or otherwise convertible groups and are rapidly transformed in vivo to yield the parent compound (also called the active metabolite), for example, by hydrolysis in blood or by activation via oxidation as in case of thioether groups. Most common prodrugs include esters and amide analogues of the parent compounds. The prodrug is formulated with the objectives of improved chemical stability, improved patient acceptance and compliance, improved bioavailability, prolonged duration of action, improved organ selectivity, improved formulation (e.g., increased hydrosolubility), and/or decreased side effects (e.g., toxicity). In general, prodrugs themselves have weak or no biological activity and are stable under ordinary conditions. Prodrugs can usually be readily prepared from the parent compounds using methods known in the art.

The medicament preparation according to the present invention preferably comprises the active substance or a pharmaceutically acceptable salt thereof. The medicament preparation preferably is a fluid or liquid, in particular comprising the active substance or the pharmaceutically acceptable salt thereof. The medicament preparation preferably comprises one or more solvents, in particular water, alcohol, ethanol or the like. The medicament preparation in particular is a solution and/or suspension from the active substance or a pharmaceutically acceptable salt thereof, in particular an aquenous, alcoholic, and/or ethanolic solution and/or suspension.

In a further aspect of the present invention, which can also be realized independently, an aerosol is produced with the insert, the reservoir, the nebulizer and/or the inhaler according to the present invention, from or with the medicament preparation comprising the active substance or a pharmaceutically acceptable salt thereof. It has been surprisingly shown that producing the aerosol and administering the aerosol is particularly efficient and effective in this case. In particular, the amount of the active substance or the pharmaceutically acceptable salt thereof that can be resorbed by a lung can be increased by means of the combination of the liquid medicament preparation comprising the active substance and the insert, the reservoir, the nebulizer and/or the inhaler for generating the aerosol with the medicament preparation and, preferably the chamber forming a spacer, preferably with the respiratory orifice adapter.

The aspects mentioned above and described hereinafter can be implemented individually and in combination and also independently of one another. In particular, it is possible that the inhaler with the operating lever, the inhaler with the reservoir with the valve uppermost in the position of use, the inhaler with the operating lever and the reservoir with the valve uppermost in the position of use, the inhaler with the operating lever and the discharge nozzle with the direction of discharge at an angle relative to the central axis of the reservoir, the inhaler with the nebulizer, the nebulizer with the discharge nozzle, the nebulizer with the counter, the nebulizer with the discharge nozzle and the counter, the discharge nozzle with the activating device, the discharge nozzle with the activating device in conjunction with the nebulizer, the nebulizer with the inhaler, the discharge nozzle with the inhaler, and other combinations of the different aspects constitute independent inventions and are therefore implemented separately, independently of one another or in combination.

Further aspects, advantages and properties of the present invention will be apparent from the claims and the drawings and the following description of preferred embodiments.

