CA2415849C - Pharmaceutical powder cartridge, and inhaler equipped with same - Google Patents
Pharmaceutical powder cartridge, and inhaler equipped with same Download PDFInfo
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- CA2415849C CA2415849C CA002415849A CA2415849A CA2415849C CA 2415849 C CA2415849 C CA 2415849C CA 002415849 A CA002415849 A CA 002415849A CA 2415849 A CA2415849 A CA 2415849A CA 2415849 C CA2415849 C CA 2415849C
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- pharmaceutical powder
- powder cartridge
- metering
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- cartridge according
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0065—Inhalators with dosage or measuring devices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0001—Details of inhalators; Constructional features thereof
- A61M15/0003—Details of inhalators; Constructional features thereof with means for dispensing more than one drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0065—Inhalators with dosage or measuring devices
- A61M15/0068—Indicating or counting the number of dispensed doses or of remaining doses
- A61M15/007—Mechanical counters
- A61M15/0071—Mechanical counters having a display or indicator
- A61M15/0073—Mechanical counters having a display or indicator on a ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2202/00—Special media to be introduced, removed or treated
- A61M2202/06—Solids
- A61M2202/064—Powder
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Anesthesiology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicinal Preparation (AREA)
- Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
- Basic Packing Technique (AREA)
- Materials For Medical Uses (AREA)
- External Artificial Organs (AREA)
Abstract
To improve administration of powdered pharmaceuticals, a pharmaceutical powder cartridge (1) for powder inhalers for holding a pharmaceutical depot for a large number of pharmaceutical powder doses is proposed, having at least one storage space (6) and an integrated metering device, said integrated metering device comprising at least one metering slide (9, 13, 14) which can be moved approximately transversely in a metering slide channel (12) at least from a filling position to an emptying position, approximately transversely with respect to the direction of flow of the pharmaceutical powder out from the at least one storage space (6), said metering slide channel (12) with the at least one metering slide (9, 13, 14) being sealed off from the environment at least in the filling position of the metering slide (9, 13, 14), and also further measures and a corresponding inhaler.
Description
Pharmaceutical powder cartridge, and inhaler equipped with same Description The invention relates to a pharmaceutical powder cartridge for powder inhalers for holding a pharmaceutical depot for a large number of pharmaceutical powder doses, having at least one storage space and an integrated metering device, said integrated metering device comprising at least one metering slide which can be moved approximately transversely in a metering slide channel at least from a filling position to an emptying position, approximately transversely with respect to the direction of flow of the pharniaceutical powder out from the at least one storage space, and an inhaler equipped accordingly.
Background of the invention In the field of treatment of bronchial diseases, and also of other diseases in which medication can be given via the airways, it is known not only to atomize solutions or suspensions into inhalable aerosols but also to administer powdered medicaments. Many examples of such medicaments are described in the literature, and of these we refer purely by way of illustration to WO 93/11773, EP 0 416 950 Al and EP 0 416 951 Al.
A customary form of administration in this connection is delivery via an inhalation device (inhaler).
Known inhalers for powdered pharmaceuticals include those for administration of a single dose and also inhalation devices which have a storage space for a plurality of pharmaceutical doses. In connection with the latter, it is known either to provide separate storage spaces for each indi.vidual dose or to provide one single receiving space for receiving a multiplicity of doses of a medicament.
Known inhalers in which a large number of individual doses are provided in separate storage spaces include those in which individual areas of the inhaler are each filled with a pharmaceutical ciose. An example of such an inhaler is described in US 5,301,666 A. However, it is also known to accommodate a large number of pharmaceutical powder doses in separate areas of what are called blister packs. An example of such a blister pack for use with an inhaler is described in DE 44 00 083 C2. Such a blister pack, which is designed at the same time as a disposable irihaler, is described for example in DE 44 00 084 Al.
An inhalation device into which blister packs can be inserted, which each have separate storage spaces for individual doses of a powdered pharmaceutical and which can be emptied one after another with the aid of the inhalation device, is described, for example, in DE 195 23 516 Cl.
Many examples of inhalers with a storage space for a large number of pharmaceutical doses are described in the prior art. One example with an exchangeable storage container is described in German Patent Specification 846 770, and another in WO 95/31237.
An important problem with inhalation systems in which a large number of doses of a medically active substance are accommodated in a common storage space concerns the apportioning of an individual dose for one individual inhalation. In this connection, a great many solutions have been proposed, for example those which are described in US 2,587,215 A and US 4,274,403 A. Other types of arrangements for metering an individual dose of pharmaceutical powder from a storage space for a large number of pharmaceutical doses are furthermore described in WO 92/09322, WO 93/16748 and DE 35 35 561 C2 and in GB 2 165 159 A. An excharigeable cartridge for receiving a large riurnber of doses of a pharmaceutical powder with an integrated metering slide is known from DE 195 22 415 Al.
Another important problem with inhalation of pharmaceutical powders concerris the breakdown of the galenic powder formulations into particles which can access the lungs. The active substances administered in this way are generally combined with vehicles in order to achieve a reasonable dosing capacity of the medically active substance and to set further properties of the pharmaceutical powder, which for example can influence the storage life.
Proposed solutions concerning the designs of powder inhalers with which particles which can access the lungs are intended to be made available in an air stream for inhalation are described for example in EP 0 640 354 A2, US 5,505,196 A, US 5,320,714 A, US
5,435,301 A, US 5, 301, 666 A, DE 195 22 416 Al and WO
97/00703. Proposals are also known to use auxiliary energy to generate the air stream, for example in ZA-A
916741.
In the use of medicaments for inhalation in powder form, it is also quite generally known to combine active substances by administering prepared active substance mixtures. Corresponding proposals are found in EP 0 416 951 Al and WO 93/11773, for example for combination of salmeterol and fluticasone or formoterol and budesonide.
Background of the invention In the field of treatment of bronchial diseases, and also of other diseases in which medication can be given via the airways, it is known not only to atomize solutions or suspensions into inhalable aerosols but also to administer powdered medicaments. Many examples of such medicaments are described in the literature, and of these we refer purely by way of illustration to WO 93/11773, EP 0 416 950 Al and EP 0 416 951 Al.
A customary form of administration in this connection is delivery via an inhalation device (inhaler).
Known inhalers for powdered pharmaceuticals include those for administration of a single dose and also inhalation devices which have a storage space for a plurality of pharmaceutical doses. In connection with the latter, it is known either to provide separate storage spaces for each indi.vidual dose or to provide one single receiving space for receiving a multiplicity of doses of a medicament.
Known inhalers in which a large number of individual doses are provided in separate storage spaces include those in which individual areas of the inhaler are each filled with a pharmaceutical ciose. An example of such an inhaler is described in US 5,301,666 A. However, it is also known to accommodate a large number of pharmaceutical powder doses in separate areas of what are called blister packs. An example of such a blister pack for use with an inhaler is described in DE 44 00 083 C2. Such a blister pack, which is designed at the same time as a disposable irihaler, is described for example in DE 44 00 084 Al.
An inhalation device into which blister packs can be inserted, which each have separate storage spaces for individual doses of a powdered pharmaceutical and which can be emptied one after another with the aid of the inhalation device, is described, for example, in DE 195 23 516 Cl.
Many examples of inhalers with a storage space for a large number of pharmaceutical doses are described in the prior art. One example with an exchangeable storage container is described in German Patent Specification 846 770, and another in WO 95/31237.
An important problem with inhalation systems in which a large number of doses of a medically active substance are accommodated in a common storage space concerns the apportioning of an individual dose for one individual inhalation. In this connection, a great many solutions have been proposed, for example those which are described in US 2,587,215 A and US 4,274,403 A. Other types of arrangements for metering an individual dose of pharmaceutical powder from a storage space for a large number of pharmaceutical doses are furthermore described in WO 92/09322, WO 93/16748 and DE 35 35 561 C2 and in GB 2 165 159 A. An excharigeable cartridge for receiving a large riurnber of doses of a pharmaceutical powder with an integrated metering slide is known from DE 195 22 415 Al.
Another important problem with inhalation of pharmaceutical powders concerris the breakdown of the galenic powder formulations into particles which can access the lungs. The active substances administered in this way are generally combined with vehicles in order to achieve a reasonable dosing capacity of the medically active substance and to set further properties of the pharmaceutical powder, which for example can influence the storage life.
Proposed solutions concerning the designs of powder inhalers with which particles which can access the lungs are intended to be made available in an air stream for inhalation are described for example in EP 0 640 354 A2, US 5,505,196 A, US 5,320,714 A, US
5,435,301 A, US 5, 301, 666 A, DE 195 22 416 Al and WO
97/00703. Proposals are also known to use auxiliary energy to generate the air stream, for example in ZA-A
916741.
In the use of medicaments for inhalation in powder form, it is also quite generally known to combine active substances by administering prepared active substance mixtures. Corresponding proposals are found in EP 0 416 951 Al and WO 93/11773, for example for combination of salmeterol and fluticasone or formoterol and budesonide.
4 and many other publications over a period of more than twenty years have described how, particularly in powder inhalers, there is a considerable problem with moisture. Not only can moisture have a disadvantageous effect on the pharmaceutically active composition of the medicament, it can also impair in particular the interplay of physical and chemical parameters of the combination of active substance and auxiliaries. As a result, lumps may form, for example, or the breakdown of the inhaled powder into particles which can access the lungs may be impaired. All these circumstances can lead to problems affecting the metering and the efficacy of the administration of a powdered medicament.
To minimize these disadvantages, various attempts have already been made in the past to reduce the penetration of moisture into a powder inhaler by using seals.
Attempts have also been made to reduce the disadvantageous effects of penetrated moisture by providing desiccants to absorb the moisture, in particular to keep the air moisture in storage chambers to a minimum.
Prior art In the prior art, WO 00/74754 expressly describes how attempts to solve this problem have generally been made only by the use of desiccants in various forms. The Applicant there claims to have solved this problem by for the first time providing a seal intended to prevent penetration of moisture into the inhaler, particularly into the storage container of a powder inhaler with in particular elastic sealing elements.
To this end, reference is made to sealing elements made from "all conventionally known materials, for example natural or synthetic rubber, a silicone or PTFE" and like materials.
Subsequently, with reference to the "Clickhaler" powder inhaler from Innovata Biomed, an arrangement is described in detail which concerns a particular arrangement of the metering mechanism of this inhaler, which comprises a metering device in the manner of a star feeder in the form of an inclined truncated cone.
In the embodiment described;, the sealing element provided is a likewise frustoconical sealing sleeve which is fitted over the truncated metering cone and is intended to be pivotable, so that it can assume a sealing position and a non-sealing position. Here, page 5 interestingly describes how this sealing sleeve is preferably to be made of a syrithetic material like that of the metering cone. It is further proposed that the sealing sleeve be provided with the same number of holes as the metering cone element has metering cavities. The sealing sleeve and the metering element are to be designed in such a way that, when both are turned, a metering chamber formed by an opening in the sealing sleeve first takes up the medicament from the reservoir and then, upon further turning, deposits this in the metering cavity in the actual metering cone and is finally conveyed from there into an air channel.
A particularly advantageous embodimerit is described in which the outer contour of the sealing sleeve forms a spherical section and provides a good fit with a corresponding curvature of the medicament storage space. The inner contour of the sealing sleeve is intended to be adapted to the frustum of the metering cone.
From US 6,132,394 A, it is known to provide, in a medicament chamber of an inhaler, a separate container containing a desiccant. This is described as differing from US 4,274,403 A in that a completely closed separate container is used which is made of a material which is as far as possible permeable to moisture and in which the desiccant, for example silica gel, is to be placed. An important advantage of this is stated to be the fact that, compared to conventional dry capsules, there ar-e no assembly or connection points through which small amounts of the desiccant can pass into the medicament chamber and thus contaminate the powdered medicament. In conventional dry capsules, such connection points are to be present in particular between capsule body and porous membrane through which the water vapour is to pass into the desiccant.
The separate container is accordingly intended to be made as far as possible from a single material, preferably one with a high degree of water vapour permeability. Suitable materials proposed are polycarbonate (PC) and ABS (acrylonitrile-butadiene-styrene) . The drying behaviour over a relatively long period of time is intended here to be adapted via the material of the container.
WO 01/46038 discloses the use of a stopper, a foil, a tablet or a lining of an EVA copolymer with 35-80% by weight of a desiccant such as silica gel, clay or zinc chloride as desiccant capsule or embedded in a storage container in particular for packaged foods, mention being made of deficierit mechanical stability of the stopper etc., and the risk of mechanical decomposition at relatively high concentrations of desiccant. Here, the EVA types described as being suitable have quite high proportions of vinyl acetate copolymers, so that these materials have very high water vapour permeability.
WO 01/21238 discloses a powder inhaler with hermetic sealing when not in use. To this end, in the case of a powder inhaler with a medicanlent storage space and with an air channel running through under the storage space, a sealing skirt is provided on each side of the storage container and covers an air inlet opening and an inhalation opening of the air channel in a position of rest. When an actuating cap is actuated to move a metering plunger through the storage space in order to convey a dose of medicament from the reservoir into the air channel, the two sealiiig skirts secured on the actuating cap are moved downwards too until the metering plunger has reached its emptying position.
Through-holes are provided in the sealing skirts and are arranged in such a way that, with the actuating cap in the end position, they free the openings of the air channel. As long as the actuating cap is kept depressed, the air can be sucked through the air channel. When the actuating cap is released and returns to its starting position, the openings of the air channel are closed again.
By means of an additional guide arrangement and an elastic design of the sealing skirts, these are pressed against the outer wall in order to increase the sealing effect. In this arrangement, as the distance travelled from the opening position to the closing position increases, the sealing skirts are pressed increasingly more strongly against the outer wall of the inhaler transverse to the direction of movement. An elastic seal in the form of a bellows is also provided between actuating cap and inhaler housing in order to close the gap between said structural parts.
Summary of the invention The object of the inventiori is therefore to improve known systems for administering powdered pharmaceuticals.
According to the invention, this object is achieved by means of a pharmaceutical powder cartridge for powder inhalers for holding a pharmaceutical depot for a large number of pharmaceutical powder doses, having at least one storage space and an integrated metering device, said integrated metering device comprising at least one metering slide which can be moved approximately transversely in a metering slide channel at least from a filling position to an emptying position, approximately transversely with respect to the direction of flow of the pharmaceutical powder out from the at least one storage space, the metering slide channel with the at least one metering slide being sealed off from the environment at least in the filling position of the metering slide.
By means of the design according to the invention, and for only the slightest additional outlay, an effective protection of the pharmaceutical storage space against moisture from the environment is obtained, in particular during intermediate storage during the.
period of use after the patient has begun using the storage space. This advantage applies both while the pharmaceutical cartridge is fitted in an inhaler and also when it is being stored outside the inhaler.
Compatibility with known powder inhalers for exchangeable pharmaceutical powder cartridges of the type mentioned at the outset can be maintained.
In a particularly preferred embodiment, a pharmaceutical powder cartridge according to the invention is characterized in that the metering slide channel has, at one end, an opening to the environment through which a part of the metering slide can pass, and, around the opening, a contact surface is provided for a seal.
A particularly reliable function can be achieved if the metering slide has a sealing surface provided in a plane approximately transverse to its direction of movement from the f.illirig position to the emptying position. In this way, it is at the same time possible to avoid a change of frictional forces during the movement of the metering slide which, in known inhalers, can be caused by a movement of the seal along the sealing surface, by powder residues or wear of the seal.
To minimize these disadvantages, various attempts have already been made in the past to reduce the penetration of moisture into a powder inhaler by using seals.
Attempts have also been made to reduce the disadvantageous effects of penetrated moisture by providing desiccants to absorb the moisture, in particular to keep the air moisture in storage chambers to a minimum.
Prior art In the prior art, WO 00/74754 expressly describes how attempts to solve this problem have generally been made only by the use of desiccants in various forms. The Applicant there claims to have solved this problem by for the first time providing a seal intended to prevent penetration of moisture into the inhaler, particularly into the storage container of a powder inhaler with in particular elastic sealing elements.
To this end, reference is made to sealing elements made from "all conventionally known materials, for example natural or synthetic rubber, a silicone or PTFE" and like materials.
Subsequently, with reference to the "Clickhaler" powder inhaler from Innovata Biomed, an arrangement is described in detail which concerns a particular arrangement of the metering mechanism of this inhaler, which comprises a metering device in the manner of a star feeder in the form of an inclined truncated cone.
In the embodiment described;, the sealing element provided is a likewise frustoconical sealing sleeve which is fitted over the truncated metering cone and is intended to be pivotable, so that it can assume a sealing position and a non-sealing position. Here, page 5 interestingly describes how this sealing sleeve is preferably to be made of a syrithetic material like that of the metering cone. It is further proposed that the sealing sleeve be provided with the same number of holes as the metering cone element has metering cavities. The sealing sleeve and the metering element are to be designed in such a way that, when both are turned, a metering chamber formed by an opening in the sealing sleeve first takes up the medicament from the reservoir and then, upon further turning, deposits this in the metering cavity in the actual metering cone and is finally conveyed from there into an air channel.
A particularly advantageous embodimerit is described in which the outer contour of the sealing sleeve forms a spherical section and provides a good fit with a corresponding curvature of the medicament storage space. The inner contour of the sealing sleeve is intended to be adapted to the frustum of the metering cone.
From US 6,132,394 A, it is known to provide, in a medicament chamber of an inhaler, a separate container containing a desiccant. This is described as differing from US 4,274,403 A in that a completely closed separate container is used which is made of a material which is as far as possible permeable to moisture and in which the desiccant, for example silica gel, is to be placed. An important advantage of this is stated to be the fact that, compared to conventional dry capsules, there ar-e no assembly or connection points through which small amounts of the desiccant can pass into the medicament chamber and thus contaminate the powdered medicament. In conventional dry capsules, such connection points are to be present in particular between capsule body and porous membrane through which the water vapour is to pass into the desiccant.
The separate container is accordingly intended to be made as far as possible from a single material, preferably one with a high degree of water vapour permeability. Suitable materials proposed are polycarbonate (PC) and ABS (acrylonitrile-butadiene-styrene) . The drying behaviour over a relatively long period of time is intended here to be adapted via the material of the container.
WO 01/46038 discloses the use of a stopper, a foil, a tablet or a lining of an EVA copolymer with 35-80% by weight of a desiccant such as silica gel, clay or zinc chloride as desiccant capsule or embedded in a storage container in particular for packaged foods, mention being made of deficierit mechanical stability of the stopper etc., and the risk of mechanical decomposition at relatively high concentrations of desiccant. Here, the EVA types described as being suitable have quite high proportions of vinyl acetate copolymers, so that these materials have very high water vapour permeability.
WO 01/21238 discloses a powder inhaler with hermetic sealing when not in use. To this end, in the case of a powder inhaler with a medicanlent storage space and with an air channel running through under the storage space, a sealing skirt is provided on each side of the storage container and covers an air inlet opening and an inhalation opening of the air channel in a position of rest. When an actuating cap is actuated to move a metering plunger through the storage space in order to convey a dose of medicament from the reservoir into the air channel, the two sealiiig skirts secured on the actuating cap are moved downwards too until the metering plunger has reached its emptying position.
Through-holes are provided in the sealing skirts and are arranged in such a way that, with the actuating cap in the end position, they free the openings of the air channel. As long as the actuating cap is kept depressed, the air can be sucked through the air channel. When the actuating cap is released and returns to its starting position, the openings of the air channel are closed again.
By means of an additional guide arrangement and an elastic design of the sealing skirts, these are pressed against the outer wall in order to increase the sealing effect. In this arrangement, as the distance travelled from the opening position to the closing position increases, the sealing skirts are pressed increasingly more strongly against the outer wall of the inhaler transverse to the direction of movement. An elastic seal in the form of a bellows is also provided between actuating cap and inhaler housing in order to close the gap between said structural parts.
Summary of the invention The object of the inventiori is therefore to improve known systems for administering powdered pharmaceuticals.
According to the invention, this object is achieved by means of a pharmaceutical powder cartridge for powder inhalers for holding a pharmaceutical depot for a large number of pharmaceutical powder doses, having at least one storage space and an integrated metering device, said integrated metering device comprising at least one metering slide which can be moved approximately transversely in a metering slide channel at least from a filling position to an emptying position, approximately transversely with respect to the direction of flow of the pharmaceutical powder out from the at least one storage space, the metering slide channel with the at least one metering slide being sealed off from the environment at least in the filling position of the metering slide.
By means of the design according to the invention, and for only the slightest additional outlay, an effective protection of the pharmaceutical storage space against moisture from the environment is obtained, in particular during intermediate storage during the.
period of use after the patient has begun using the storage space. This advantage applies both while the pharmaceutical cartridge is fitted in an inhaler and also when it is being stored outside the inhaler.
Compatibility with known powder inhalers for exchangeable pharmaceutical powder cartridges of the type mentioned at the outset can be maintained.
In a particularly preferred embodiment, a pharmaceutical powder cartridge according to the invention is characterized in that the metering slide channel has, at one end, an opening to the environment through which a part of the metering slide can pass, and, around the opening, a contact surface is provided for a seal.
A particularly reliable function can be achieved if the metering slide has a sealing surface provided in a plane approximately transverse to its direction of movement from the f.illirig position to the emptying position. In this way, it is at the same time possible to avoid a change of frictional forces during the movement of the metering slide which, in known inhalers, can be caused by a movement of the seal along the sealing surface, by powder residues or wear of the seal.
Particularly reliable sealing is achieved if said sealing is provided by an elastic seal.
In the case of prolonged storage prior to the pharmaceutical powder cartridge being inserted into an inhaler, an especially permanent and effective sealing is guaranteed if the metering slide can further be moved into an additional storing position and the seal is elastically prestressed sealingly at least in the storing position of the metering slide, especially if the metering slide is fixed iri the storing position by resiliently elastic means.
In a preferred embodiment, a pharmaceutical powder cartridge according to the invention is characterized in that the metering device comprises at least one metering cavity for holding a predetermined quantity of a pharmaceutical powder.
For administering active substance combinations, it can also be advantageous if the pharmaceutical powder cartridge has at least two storage spaces, in particular if the pharmaceutical powder cartridge has a metering device, said metering device having, for each of the storage spaces, a metering cavity for apportioning a predetermined quantity of each medically active substance provided in the storage spaces.
Depending on the active substance combination provided, it is also advantageous if the metering devices of the individual pharmaceutical powder cartridges have metering cavities of identical or different volume.
A particularly economical application, especially suitable for expensive pharmaceutical powders with only occasional administration, is possible if the pharmaceutical powder cartridge further has a device for indicating the quantity of pharmaceutical doses which remain in the storage chambers or which have been removed from the storage chambers.
In the case of prolonged storage prior to the pharmaceutical powder cartridge being inserted into an inhaler, an especially permanent and effective sealing is guaranteed if the metering slide can further be moved into an additional storing position and the seal is elastically prestressed sealingly at least in the storing position of the metering slide, especially if the metering slide is fixed iri the storing position by resiliently elastic means.
In a preferred embodiment, a pharmaceutical powder cartridge according to the invention is characterized in that the metering device comprises at least one metering cavity for holding a predetermined quantity of a pharmaceutical powder.
For administering active substance combinations, it can also be advantageous if the pharmaceutical powder cartridge has at least two storage spaces, in particular if the pharmaceutical powder cartridge has a metering device, said metering device having, for each of the storage spaces, a metering cavity for apportioning a predetermined quantity of each medically active substance provided in the storage spaces.
Depending on the active substance combination provided, it is also advantageous if the metering devices of the individual pharmaceutical powder cartridges have metering cavities of identical or different volume.
A particularly economical application, especially suitable for expensive pharmaceutical powders with only occasional administration, is possible if the pharmaceutical powder cartridge further has a device for indicating the quantity of pharmaceutical doses which remain in the storage chambers or which have been removed from the storage chambers.
The advantages of the invention can be used especially in long-term use of a pharmaceutical powder cartridge for powder inhalers for holding a pharmaceutical depot for a large number of pharmaceutical powder doses, having at least one storage space and an integrated metering device, said integrated metering device being able to assume at least a filling position and an emptying position and being able to move from the filling position to the emptying position, and with a seal being provided which substantially seals off the storage space from the envir.orlment and against entry of moisture, at least in the filling position of the metering device, said seal being elastically deformable, during a movement of the metering device from its emptying position to its filling position, without any sliding movement of the seal relative to the sealing surfaces.
In a preferred embodiment of the invention, the seal is made of a silicone rubber or an elastomer, more preferably a thermoplastic elastomer, preferably of TPEE (thermoplastic polyester elastomer).
The improvement in the application properties afforded by the invention, particularly through actively reducing the effect of moisture on a pharmaceutical powder during the period of use by a patient or a hospital establishment, is further achieved by means of a pharmaceutical powder cartridge for powder inhalers or a powder inhaler having at least one storage space for holding a pharmaceutical depot for a large number of pharmaceutical powder doses, including a housing body and a lid which substantially enclose the at least one storage space, and where the housing body and/or the lid are made predominantly of a PVDC
(polyvinylidene chloride), a pharmaceutically compatible plasti_c coated completely or partially with PVDC, an olefin copo]ymer with heterocyclic side groups - 1.1 -(COC or mPP), or a PCTFE (polychloro-trifluoroethylene).
In a particularly advantageous embodiment, a pharmaceutical powder cartridge according to the invention is characterized in that at least one metering slide as a component of the rnetering device is made predominantly of a PVDC (polyvinylidene chloride), a pharmaceutically compatible plastic coated completely or partially with PVDC, an olefin copolymer with heterocyclic side groups, an at least partially oriented PP (polypropylene) or a PCTFE (polychloro-trifluoroethylene).
To limit the effects of moisture, which has penetrated into the cartridge or is present therein, on a pharmaceutical powder, it is further expedient if a pharmaceutical powder cartridge for powder inhalers or a powder inhaler according to the invention is characterized in that the housing body and/or lid comprises, on at least part of the side facing the storage space, a blend of desiccant embedded in a thermoplastic matrix.
To avoid impairment of the pharmaceutical by desiccant residues, it is advantageous, according to the invention, to provide a pharrnaceutical powder cartridge for powder inhalers or a powder inhaler having at least one storage space for holding a pharmaceutical powder depot for a large number of pharmaceutical doses, containing at least one shaped body made of a blend of a thermoplastic matrix with a desiccant embedded therein, preferably silica gel, bentonite or molecular sieve, particularly if' channels are formed in a matrix of a thermoplastic of low water absorption, as are obtainable by dissolving soluble co-extrudate components. For rapid uptake of residual moisture in the storage space, it can also be expedient in this case if fibres which absorb water vapour are embedded as filler in a matrix of a thermoplastic of low water absorption.
It is particularly advantageous, for economic mass production, if the blend in a matrix of a thermoplastic of low water absorption and a desiccant embedded therein is designed at least as part of an inner wall of a storage space by multi-component injection-moulding in a housing body made of a plastic substantially impermeable to water vapour.
Within the meaning of the invention, it is further advantageous if housing body and lid are sealed watertight, preferably by ultrasonic welding.
For particularly economic production, the seal is co-injected onto the housing body or the metering'slide.
The invention can be advantageously exploited in economic terms using an inhaler for powdered pharmaceuticals with a pharmaceutical powder cartridge according to the invention, and with an inhaler for powdered pharmaceuticals, in which the pharmaceutical can be taken by a patient by way of an air stream, characterized by a holder for a pharmaceutical powder cartridge according to the invention.
The advantages of the invention are particularly beneficial for patients requiring treatment with a pharmaceutical powder cartridge according to the invention containing a powder with one or more of the following active substances: analgesics, anti-allergics, antibiotics, anticholinergics, anti-histamines, anti-inflammatory substances, antipyretics, corticoids, steroids, antitussives, bronchodilators, diuretics, enzymes, substances acting on the cardiovascular system, hormones, proteins and peptides.
Application of the invention By means of the invention, i.t is possible to make available pharmacodynamically active substances in the form of powdered pharmaceuticals over a long period of use, even when they are sensitive to moisture or are under unfavourable climatic c:oriditions, and in so doing also to obtain the advantages of re-usable inhalers with exchangeable pharmaceutical powder cartridges.
It is also possible to make available powdered pharmaceuticals for inhalation in different active substance combinations under improved storage conditions, of which individual active substances have increased sensitivity to moisture affecting their storage life, their stability or their dosability.
Active substances for which the invention can be used can also be for example from the group of beta-sympathomimetics: salbutamol, reproterol, fenoterol, formoterol, salmeterol. Possible examples from the group of corticosteroids are: budesonide, beclomethasone, fluticasone, triamcinolone, loteprednol, mometasone, flunisolide, ciclosonide.
Possible examples froni the group of anticholinergics are: ipatropium bromide, thiotropium bromide, glycopyrrolate.
Possible examples from the group of analgesics and anti-migraines are: morphine, tramadol, flupirtine, sumatryptan. The following can be used for example from the group of peptides and proteins: cetrorelix, insulin, calcitonin, parathyroid hormone, factor VIII
analogs, interferon alpha, interferon beta, heparin, FSH (follicle-stimulating hormone), colistin, tobramycin.
Use is not limited to the active substances mentioned here. The pharmaceutical powder cartridge described is suitable for all active substances which can be metered in powder form and administered by inhalation. By appropriate modification of the system and of the metering device, the inventi_on described is also suitable for combination of active substances which contain liquid formulations, for example solutions or suspensions of pharmacodynamically active substances.
Pharmaceutical powder formulations which can expediently be used with the pharmaceutical powder cartridge system according to the invention can contain various active substances, such as, for example, analgesics, anti-allergics, antibiotics, anticholinergics, antihistamines, anti-inflammatory substances, antipyretics, corticoids, steroids, antitussives, bronchodilators, diuretics, enzymes, cardiovascular agents, hormones, proteins and peptides.
Examples of analgesics are codeine, diamorphine, dihydromorphine, ergotamine, fentanyl and morphine;
examples of anti-allergics are cromoglycinic acid and nedocromil; examples of antibiotics are cephalosporins, fusafungine, neomycin, penicillins, pentamidine, streptomycin, sulphonamides and tetracyclines, colistin, tobramycin; examples of anticholinergics are atropine, atropine methonitrate, ipratropium bromide, oxitropium bromide, trospium chloride and thiotropium bromide; examples of antihistamines are azelastine, flezelastine and methapyrilene; examples of anti-inflammatory substances are beclomethasone, budesonide, loteprednol, dexamethasone, flunisolide, fluticasone, tipredane, triamcinolone, mometasone; examples of antitussives are narcotine and noscapine; examples of bronchodilators are bambuterol, bitolterol, carbuterol, clenbuterol, ephedrine, epinephrine, formoterol, fenoterol, hexoprerialine, i.buterol, isoprenaline, isoproterenol, metaproterenol, orciprenaline, phenylephrine, phenylpropanolamine, pirbuterol, procaterol, reproterol, rimiterol, salbutamol, salmeterol, sulfonteros, terbutaline and tolobuterol;
examples of diuretics are amiloride and furosemide; an example of an enzyme is trypsin; examples of cardiovascular agents are diltiazem and nitroglycerin;
examples of hormones are cortisone, hydrocortisone and prednisolone; examples of proteins and peptides are cyclosporine, cetrorelix, glucagon and insulin. Further active substances which can be used are adrenochrome, coichicine, heparin, scopolamine. The active substances listed by way of example can be used as free bases or acids or as pharmaceutically acceptable salts.
Counterions which can be used include, for example, physiological alkaline earth metals or alkali metals or amines, for example acetate, benzene sulphonate, benzoate, hydrogen carbonate, hydrogen tartrate, bromide, chloride, iodide, carbonate, citrate, fumarate, malate, maleate, cluconate, lactate, pamoate and sulphate. Esters can also be used, for example acetate, acetonide, propionate, dipropionate, valerate.
The invention also allows the doctor to very accurately adapt the dose to the patient over a long period of time, without the need to dispose of partially emptied cartridges, which would have a disadvantageous effect on treatment costs, and without compromising compatibility with other cartridges with different metering devices, e.g. with the cartridge known from WO
97/00703.
Brief description of the drawings Figure 1 shows a pharmaceutical powder cartridge according to the invention, in a perspective view;
Figure 2 shows a plan view of a seal of a pharmaceutical powder cartridge according to the invention;
Figure 3 shows a view of a carrier mechanism of a metering slide in a pharmaceutical powder cartridge according to the invention;
Figure 4A shows a view of a metering slide body in a pharmaceutical powder cartridge according to the invention;
Figure 4B shows a longitudinal section through the metering slide body of a pharmaceutical powder cartridge according to the invention from Figure 4A;
Figure 5 shows a longitudinal section through a pharmaceutical powder cartridge according to the invention, in an inhaler with the metering slide in the emptying position; and Figure 6 shows a longitudinal section through a pharmaceutical powder cartridge according to the invention, in an inhaler with the metering slide in the filling position.
Description of preferred illustrative embodiments Fig. 1 shows a perspective view of a housing body 11 of a pharmaceutical powder cartridge 1 according to the invention for exchangeable insertion into a powder inhaler 2. The pharmaceutical powder cartridge 1 shown here has, at the upper area of its housing body 11, an edge 3 which includes two grip areas 4 in order to permit easy insertion of the pharmaceutical powder cartridge 1 into a powder inhaler 2. In the illustrative embodiment shown, a device for indicating the amount of pharmaceutical doses which remain in the storage space 6 or have been removed from the storage space 6 is provided at the same time in the edge 3, in an annular channel 5 formed therein (the device is not shown in detail however), for example in the form of foil strips with corresponding markings as is described in detail in WO 97/00703. The user can then read off the markings through the viewing window 7 in the edge 3.
The edge 3 also serves to receive a lid 8 with which the storage space 6-forming the main part of the pharmaceutical powder cartridge 1 can be sealed off.
Such a lid 8 is expediently sealed in a watertight manner to a collar 10 formed within the edge 3, for example by ultrasonic welding.
Arranged below the storage space 6 there is a metering slide channel 12 in which a metering slide acting as metering device is movably arranged, which metering slide, in the illustrative embodiment described here,-is made up of three parts, namely a carrier 13, the actual metering slide body 1.4, and a seal 15 (Figures 2, 3, 4A and 4B). The metering slide is configured in such a way that 'the seal 15 shown in Figure 2 is inserted into the carrier 13 shown in Figure 3 and the carrier 13 is clipped with seal 15 onto the metering slide body 14.
As can be clearly seen from Figure 1, the metering slide channel 12 at one end has an opening 16 and-, formed around the opening 16, there is a contact-surface 17 for the seal 15 of the metering slide. The contact surface 17 is at the same time provided as a sealing surface and extends in a plane approximately perpendicular to the direction of movement of the metering slide from a filling position, as is shown in Figure 6, to an emptying position, as is shown in Figure 5.
The metering slide body 14 shown in Figures 4A and 4B
comprises a metering cavity 18 whose holding volume represents the dose quantity to be made available for an inhalation. The seal 15 can for example be co-injected in multi-component injection-moulding and for this purpose can be made, for example, of a thermoplastic elastomer.
Correspondingly, a sealing surface can be provided on the metering slide and the elastic seal 15 can be mounted or better still injection-moulded in the area of the opening 16 of the metering slide channel 12.
The housing body 11 and/o.r the lid 8 and/or the metering slide body 14 can advantageously be made of a COC by injection-moulding. A suitable material with the name TOPASO 8007 is commercially available as a trial product from the company Ticona in Germany.
For pharmaceutical combinations in which the powders cannot be stored, or cannot adequately be stored, as a mixture, it can also be expedient to provide two storage chambers instead of the one storage space 6.
Figures 5 and 6 show a longitudinal section through the pharmaceutical powder cartridge 1 inserted into an inhaler 2. As can be seen from the figures, the metering slide, designated overall by 9, can move in the metering slide channel 12 at least from the filling position shown in Figure 6 to the emptying position shown in Figure 5.
In the filling position shown in Figure 6, pharmaceutical powder can fall. from the storage space 6 into the metering cavity 18. When the metering cavity 18 has been filled, as desired, with a pharmaceutical powder, the metering slide 9 can be moved to the emptying position shown in E'igure 5 with the aid of engagement means in a powder inhaler which are only indicated schematically here, for example such as those described in US 5,840,279 A, and which cooperate with the carrier 13.
The emptying position is reached when the metering cavity 18 is situated over an emptyirig opening 19. When the metering slide 9 has reached this position, the pharmaceutical powder can fall from the metering cavity 18 through the emptying opening 19, for example into a powder channel 20 of an inhaler 2.
The filling position of the metering slide 9 can be seen clearly in Figure 6, with the metering cavity 18 under a hole 21 on the underside of the storage space 6. To reach the empting position, the metering slide 9 is pushed to the left in Figure 6 until this metering cavity 18 covers the emptying opening 19 and the pharmaceutical powder can fall down from it.
It can also be clearly seen in Figure 6 that the seal of the metering slide 9 lies on the contact surface 17 of the metering slide channel 12 and ensures a good sealing, preferably with slight elastic deformation.
15 This can be done by prestressing with resiliently elastic means, in particular via an actuating device in the inhaler for the metering slide 9, which expediently also effects an immediate reverse movement of the metering slide 9 from the emptying position, as shown in Figure 5, to its sealed filling position, as shown in Figure 6, as soon as a pharmaceutical dose has been removed.
For a higher contact pressure of the seal 15 of the metering slide 9 on the contact surface 17 of the metering slide channel 12, and thus for a particularly reliable sealing during storage of a pharmaceutical powder cartridge according to the invention, especially prior to its first use in a powder inhaler, it is advantageous to provide, slightly further to the right in the view in Figure 6, an additional storing position for the metering slide 9 of a filled pharmaceutical powder cartridge 1 in which the metering slide 9 can be fixed by the releasable snap connection 22 shown. In this storing position, the seal 15 of the metering slide 9 on the contact surface 17 of the metering slide channel 12 is subject to an increased prestressing force.
In the upper area of the storage space there is also advantageously a shaped body 23 which is preferably secured in its position via corresponding shaped edges 24, in order to avoid mechanical loading of the pharmaceutical powder. The shaped body 23 is expediently produced by injection-moulding from a blend of a thermoplastic matrix and a desiccant. The desiccant is intended in particular to absorb moisture which is situated in the storage space 6 or which has penetrated through the metering cavity 18. The use of such a shaped body 23 ensures that no crumbs of the desiccant, typically silica gel, can pass into the pharmaceutical powder and thus into the airways of a patient. Such a shaped body can be made of a PP matrix which itself does not take up water and which is injected mixed with a water-soluble compound and the desiccant, for example polyethylene glycol, and the water-soluble compound is then washed out. This results in a sponge-like structure with channels which, after the shaped body has dried, permit rapid water absorption of the (not water-soluble) silica gel through large surfaces using capillary condensation.
In order to obtain a rapid water absorption in the whole shaped body 23, it may also be expedient to embed suitable fibres as filler in the blend of desiccant and thermoplastic matrix, which fibres, by means of their capillary action, ensure rapid transport of the air moisture and of the water to the desiccant.
The shaped body 23 can also be designed in the form of a wall lining in the manner of an itisert, as is shown purely by way of example iri Figure 5, or, by multi-component injection-mouldirig in the production of the pharmaceutical powder cartridge, can form all or part of an inner wal.l of the storage space 6.
In a preferred embodiment of the invention, the seal is made of a silicone rubber or an elastomer, more preferably a thermoplastic elastomer, preferably of TPEE (thermoplastic polyester elastomer).
The improvement in the application properties afforded by the invention, particularly through actively reducing the effect of moisture on a pharmaceutical powder during the period of use by a patient or a hospital establishment, is further achieved by means of a pharmaceutical powder cartridge for powder inhalers or a powder inhaler having at least one storage space for holding a pharmaceutical depot for a large number of pharmaceutical powder doses, including a housing body and a lid which substantially enclose the at least one storage space, and where the housing body and/or the lid are made predominantly of a PVDC
(polyvinylidene chloride), a pharmaceutically compatible plasti_c coated completely or partially with PVDC, an olefin copo]ymer with heterocyclic side groups - 1.1 -(COC or mPP), or a PCTFE (polychloro-trifluoroethylene).
In a particularly advantageous embodiment, a pharmaceutical powder cartridge according to the invention is characterized in that at least one metering slide as a component of the rnetering device is made predominantly of a PVDC (polyvinylidene chloride), a pharmaceutically compatible plastic coated completely or partially with PVDC, an olefin copolymer with heterocyclic side groups, an at least partially oriented PP (polypropylene) or a PCTFE (polychloro-trifluoroethylene).
To limit the effects of moisture, which has penetrated into the cartridge or is present therein, on a pharmaceutical powder, it is further expedient if a pharmaceutical powder cartridge for powder inhalers or a powder inhaler according to the invention is characterized in that the housing body and/or lid comprises, on at least part of the side facing the storage space, a blend of desiccant embedded in a thermoplastic matrix.
To avoid impairment of the pharmaceutical by desiccant residues, it is advantageous, according to the invention, to provide a pharrnaceutical powder cartridge for powder inhalers or a powder inhaler having at least one storage space for holding a pharmaceutical powder depot for a large number of pharmaceutical doses, containing at least one shaped body made of a blend of a thermoplastic matrix with a desiccant embedded therein, preferably silica gel, bentonite or molecular sieve, particularly if' channels are formed in a matrix of a thermoplastic of low water absorption, as are obtainable by dissolving soluble co-extrudate components. For rapid uptake of residual moisture in the storage space, it can also be expedient in this case if fibres which absorb water vapour are embedded as filler in a matrix of a thermoplastic of low water absorption.
It is particularly advantageous, for economic mass production, if the blend in a matrix of a thermoplastic of low water absorption and a desiccant embedded therein is designed at least as part of an inner wall of a storage space by multi-component injection-moulding in a housing body made of a plastic substantially impermeable to water vapour.
Within the meaning of the invention, it is further advantageous if housing body and lid are sealed watertight, preferably by ultrasonic welding.
For particularly economic production, the seal is co-injected onto the housing body or the metering'slide.
The invention can be advantageously exploited in economic terms using an inhaler for powdered pharmaceuticals with a pharmaceutical powder cartridge according to the invention, and with an inhaler for powdered pharmaceuticals, in which the pharmaceutical can be taken by a patient by way of an air stream, characterized by a holder for a pharmaceutical powder cartridge according to the invention.
The advantages of the invention are particularly beneficial for patients requiring treatment with a pharmaceutical powder cartridge according to the invention containing a powder with one or more of the following active substances: analgesics, anti-allergics, antibiotics, anticholinergics, anti-histamines, anti-inflammatory substances, antipyretics, corticoids, steroids, antitussives, bronchodilators, diuretics, enzymes, substances acting on the cardiovascular system, hormones, proteins and peptides.
Application of the invention By means of the invention, i.t is possible to make available pharmacodynamically active substances in the form of powdered pharmaceuticals over a long period of use, even when they are sensitive to moisture or are under unfavourable climatic c:oriditions, and in so doing also to obtain the advantages of re-usable inhalers with exchangeable pharmaceutical powder cartridges.
It is also possible to make available powdered pharmaceuticals for inhalation in different active substance combinations under improved storage conditions, of which individual active substances have increased sensitivity to moisture affecting their storage life, their stability or their dosability.
Active substances for which the invention can be used can also be for example from the group of beta-sympathomimetics: salbutamol, reproterol, fenoterol, formoterol, salmeterol. Possible examples from the group of corticosteroids are: budesonide, beclomethasone, fluticasone, triamcinolone, loteprednol, mometasone, flunisolide, ciclosonide.
Possible examples froni the group of anticholinergics are: ipatropium bromide, thiotropium bromide, glycopyrrolate.
Possible examples from the group of analgesics and anti-migraines are: morphine, tramadol, flupirtine, sumatryptan. The following can be used for example from the group of peptides and proteins: cetrorelix, insulin, calcitonin, parathyroid hormone, factor VIII
analogs, interferon alpha, interferon beta, heparin, FSH (follicle-stimulating hormone), colistin, tobramycin.
Use is not limited to the active substances mentioned here. The pharmaceutical powder cartridge described is suitable for all active substances which can be metered in powder form and administered by inhalation. By appropriate modification of the system and of the metering device, the inventi_on described is also suitable for combination of active substances which contain liquid formulations, for example solutions or suspensions of pharmacodynamically active substances.
Pharmaceutical powder formulations which can expediently be used with the pharmaceutical powder cartridge system according to the invention can contain various active substances, such as, for example, analgesics, anti-allergics, antibiotics, anticholinergics, antihistamines, anti-inflammatory substances, antipyretics, corticoids, steroids, antitussives, bronchodilators, diuretics, enzymes, cardiovascular agents, hormones, proteins and peptides.
Examples of analgesics are codeine, diamorphine, dihydromorphine, ergotamine, fentanyl and morphine;
examples of anti-allergics are cromoglycinic acid and nedocromil; examples of antibiotics are cephalosporins, fusafungine, neomycin, penicillins, pentamidine, streptomycin, sulphonamides and tetracyclines, colistin, tobramycin; examples of anticholinergics are atropine, atropine methonitrate, ipratropium bromide, oxitropium bromide, trospium chloride and thiotropium bromide; examples of antihistamines are azelastine, flezelastine and methapyrilene; examples of anti-inflammatory substances are beclomethasone, budesonide, loteprednol, dexamethasone, flunisolide, fluticasone, tipredane, triamcinolone, mometasone; examples of antitussives are narcotine and noscapine; examples of bronchodilators are bambuterol, bitolterol, carbuterol, clenbuterol, ephedrine, epinephrine, formoterol, fenoterol, hexoprerialine, i.buterol, isoprenaline, isoproterenol, metaproterenol, orciprenaline, phenylephrine, phenylpropanolamine, pirbuterol, procaterol, reproterol, rimiterol, salbutamol, salmeterol, sulfonteros, terbutaline and tolobuterol;
examples of diuretics are amiloride and furosemide; an example of an enzyme is trypsin; examples of cardiovascular agents are diltiazem and nitroglycerin;
examples of hormones are cortisone, hydrocortisone and prednisolone; examples of proteins and peptides are cyclosporine, cetrorelix, glucagon and insulin. Further active substances which can be used are adrenochrome, coichicine, heparin, scopolamine. The active substances listed by way of example can be used as free bases or acids or as pharmaceutically acceptable salts.
Counterions which can be used include, for example, physiological alkaline earth metals or alkali metals or amines, for example acetate, benzene sulphonate, benzoate, hydrogen carbonate, hydrogen tartrate, bromide, chloride, iodide, carbonate, citrate, fumarate, malate, maleate, cluconate, lactate, pamoate and sulphate. Esters can also be used, for example acetate, acetonide, propionate, dipropionate, valerate.
The invention also allows the doctor to very accurately adapt the dose to the patient over a long period of time, without the need to dispose of partially emptied cartridges, which would have a disadvantageous effect on treatment costs, and without compromising compatibility with other cartridges with different metering devices, e.g. with the cartridge known from WO
97/00703.
Brief description of the drawings Figure 1 shows a pharmaceutical powder cartridge according to the invention, in a perspective view;
Figure 2 shows a plan view of a seal of a pharmaceutical powder cartridge according to the invention;
Figure 3 shows a view of a carrier mechanism of a metering slide in a pharmaceutical powder cartridge according to the invention;
Figure 4A shows a view of a metering slide body in a pharmaceutical powder cartridge according to the invention;
Figure 4B shows a longitudinal section through the metering slide body of a pharmaceutical powder cartridge according to the invention from Figure 4A;
Figure 5 shows a longitudinal section through a pharmaceutical powder cartridge according to the invention, in an inhaler with the metering slide in the emptying position; and Figure 6 shows a longitudinal section through a pharmaceutical powder cartridge according to the invention, in an inhaler with the metering slide in the filling position.
Description of preferred illustrative embodiments Fig. 1 shows a perspective view of a housing body 11 of a pharmaceutical powder cartridge 1 according to the invention for exchangeable insertion into a powder inhaler 2. The pharmaceutical powder cartridge 1 shown here has, at the upper area of its housing body 11, an edge 3 which includes two grip areas 4 in order to permit easy insertion of the pharmaceutical powder cartridge 1 into a powder inhaler 2. In the illustrative embodiment shown, a device for indicating the amount of pharmaceutical doses which remain in the storage space 6 or have been removed from the storage space 6 is provided at the same time in the edge 3, in an annular channel 5 formed therein (the device is not shown in detail however), for example in the form of foil strips with corresponding markings as is described in detail in WO 97/00703. The user can then read off the markings through the viewing window 7 in the edge 3.
The edge 3 also serves to receive a lid 8 with which the storage space 6-forming the main part of the pharmaceutical powder cartridge 1 can be sealed off.
Such a lid 8 is expediently sealed in a watertight manner to a collar 10 formed within the edge 3, for example by ultrasonic welding.
Arranged below the storage space 6 there is a metering slide channel 12 in which a metering slide acting as metering device is movably arranged, which metering slide, in the illustrative embodiment described here,-is made up of three parts, namely a carrier 13, the actual metering slide body 1.4, and a seal 15 (Figures 2, 3, 4A and 4B). The metering slide is configured in such a way that 'the seal 15 shown in Figure 2 is inserted into the carrier 13 shown in Figure 3 and the carrier 13 is clipped with seal 15 onto the metering slide body 14.
As can be clearly seen from Figure 1, the metering slide channel 12 at one end has an opening 16 and-, formed around the opening 16, there is a contact-surface 17 for the seal 15 of the metering slide. The contact surface 17 is at the same time provided as a sealing surface and extends in a plane approximately perpendicular to the direction of movement of the metering slide from a filling position, as is shown in Figure 6, to an emptying position, as is shown in Figure 5.
The metering slide body 14 shown in Figures 4A and 4B
comprises a metering cavity 18 whose holding volume represents the dose quantity to be made available for an inhalation. The seal 15 can for example be co-injected in multi-component injection-moulding and for this purpose can be made, for example, of a thermoplastic elastomer.
Correspondingly, a sealing surface can be provided on the metering slide and the elastic seal 15 can be mounted or better still injection-moulded in the area of the opening 16 of the metering slide channel 12.
The housing body 11 and/o.r the lid 8 and/or the metering slide body 14 can advantageously be made of a COC by injection-moulding. A suitable material with the name TOPASO 8007 is commercially available as a trial product from the company Ticona in Germany.
For pharmaceutical combinations in which the powders cannot be stored, or cannot adequately be stored, as a mixture, it can also be expedient to provide two storage chambers instead of the one storage space 6.
Figures 5 and 6 show a longitudinal section through the pharmaceutical powder cartridge 1 inserted into an inhaler 2. As can be seen from the figures, the metering slide, designated overall by 9, can move in the metering slide channel 12 at least from the filling position shown in Figure 6 to the emptying position shown in Figure 5.
In the filling position shown in Figure 6, pharmaceutical powder can fall. from the storage space 6 into the metering cavity 18. When the metering cavity 18 has been filled, as desired, with a pharmaceutical powder, the metering slide 9 can be moved to the emptying position shown in E'igure 5 with the aid of engagement means in a powder inhaler which are only indicated schematically here, for example such as those described in US 5,840,279 A, and which cooperate with the carrier 13.
The emptying position is reached when the metering cavity 18 is situated over an emptyirig opening 19. When the metering slide 9 has reached this position, the pharmaceutical powder can fall from the metering cavity 18 through the emptying opening 19, for example into a powder channel 20 of an inhaler 2.
The filling position of the metering slide 9 can be seen clearly in Figure 6, with the metering cavity 18 under a hole 21 on the underside of the storage space 6. To reach the empting position, the metering slide 9 is pushed to the left in Figure 6 until this metering cavity 18 covers the emptying opening 19 and the pharmaceutical powder can fall down from it.
It can also be clearly seen in Figure 6 that the seal of the metering slide 9 lies on the contact surface 17 of the metering slide channel 12 and ensures a good sealing, preferably with slight elastic deformation.
15 This can be done by prestressing with resiliently elastic means, in particular via an actuating device in the inhaler for the metering slide 9, which expediently also effects an immediate reverse movement of the metering slide 9 from the emptying position, as shown in Figure 5, to its sealed filling position, as shown in Figure 6, as soon as a pharmaceutical dose has been removed.
For a higher contact pressure of the seal 15 of the metering slide 9 on the contact surface 17 of the metering slide channel 12, and thus for a particularly reliable sealing during storage of a pharmaceutical powder cartridge according to the invention, especially prior to its first use in a powder inhaler, it is advantageous to provide, slightly further to the right in the view in Figure 6, an additional storing position for the metering slide 9 of a filled pharmaceutical powder cartridge 1 in which the metering slide 9 can be fixed by the releasable snap connection 22 shown. In this storing position, the seal 15 of the metering slide 9 on the contact surface 17 of the metering slide channel 12 is subject to an increased prestressing force.
In the upper area of the storage space there is also advantageously a shaped body 23 which is preferably secured in its position via corresponding shaped edges 24, in order to avoid mechanical loading of the pharmaceutical powder. The shaped body 23 is expediently produced by injection-moulding from a blend of a thermoplastic matrix and a desiccant. The desiccant is intended in particular to absorb moisture which is situated in the storage space 6 or which has penetrated through the metering cavity 18. The use of such a shaped body 23 ensures that no crumbs of the desiccant, typically silica gel, can pass into the pharmaceutical powder and thus into the airways of a patient. Such a shaped body can be made of a PP matrix which itself does not take up water and which is injected mixed with a water-soluble compound and the desiccant, for example polyethylene glycol, and the water-soluble compound is then washed out. This results in a sponge-like structure with channels which, after the shaped body has dried, permit rapid water absorption of the (not water-soluble) silica gel through large surfaces using capillary condensation.
In order to obtain a rapid water absorption in the whole shaped body 23, it may also be expedient to embed suitable fibres as filler in the blend of desiccant and thermoplastic matrix, which fibres, by means of their capillary action, ensure rapid transport of the air moisture and of the water to the desiccant.
The shaped body 23 can also be designed in the form of a wall lining in the manner of an itisert, as is shown purely by way of example iri Figure 5, or, by multi-component injection-mouldirig in the production of the pharmaceutical powder cartridge, can form all or part of an inner wal.l of the storage space 6.
Claims (27)
1. A pharmaceutical powder cartridge for powder inhalers for holding a pharmaceutical depot for a large number of pharmaceutical powder doses, having at least one storage space and an integrated metering device, said integrated metering device comprising at least one metering slide which can be moved approximately transversely in a metering slide channel from a filling position to an emptying position, approximately transversely with respect to the direction of flow of the pharmaceutical powder out from the at least one storage space, wherein the metering slide channel with the at least one metering slide is sealed off from the environment at least in the filling position of the metering slide, and wherein the sealing is provided by an elastic seal.
2. A pharmaceutical powder cartridge according to claim 1, wherein the metering slide channel has, at one end, an opening to the environment through which a part of the metering slide can pass, and, around the opening, a contact surface is provided for a seal.
3. A pharmaceutical powder cartridge according to claim 2, wherein the metering slide has a sealing surface provided in a plane approximately transverse to its direction of movement from the filling position to the emptying position.
4. A pharmaceutical powder cartridge according to claim 1, 2 or 3, wherein the metering slide can further be moved into a storing position, and the seal is elastically prestressed sealingly at least in the storing position of the metering slide.
5. A pharmaceutical powder cartridge according to claim 4, wherein the metering slide is fixed in the storing position by resiliently elastic means.
6. A pharmaceutical powder cartridge according to any one of claims 1 to 5, wherein the metering device comprises at least one metering cavity for holding a predetermined quantity of a powdered pharmaceutical.
7. A pharmaceutical powder cartridge according to any one of claims 1 to 6, wherein the pharmaceutical powder cartridge has at least two storage spaces.
8. A pharmaceutical powder cartridge according to claim 7, wherein the pharmaceutical powder cartridge has a metering device, said metering device having, for each of the storage spaces, a metering cavity for apportioning a predetermined quantity of each medically active substance provided in the storage spaces.
9. A pharmaceutical powder cartridge according to any one of claims 1 to 8, wherein the metering devices of the individual pharmaceutical powder cartridges have metering cavities of identical or different volume.
10. A pharmaceutical powder cartridge according to any one of claims 1 to 9, wherein the pharmaceutical powder cartridge further has a device for indicating the quantity of pharmaceutical doses which remain in the at least one storage space or which have been removed from the at least one storage space.
11. A pharmaceutical powder cartridge for powder inhalers for holding a pharmaceutical depot for a large number of pharmaceutical powder doses, having at least one storage space and an integrated metering device, said integrated metering device being able to assume at least a filling position and an emptying position and being able to move from the filling position to the emptying position, wherein a seal is provided which substantially seals off the storage space from the environment and against entry of moisture, at least in the filling position of the metering device, said seal being elastically deformable, during a movement of the metering device from its emptying position to its filling position, without any sliding movement of the seal relative to the sealing surfaces.
12. A pharmaceutical powder cartridge according to any one of claims 1 to 11, wherein the seal is made of a silicone rubber or an elastomer.
13. A pharmaceutical powder cartridge according to claim 12, wherein the seal is made of a thermoplastic elastomer.
14. A pharmaceutical powder cartridge according to claim 13, wherein the thermoplastic elastomer is thermoplastic polyester elastomer (TPEE).
15. A pharmaceutical powder cartridge according to any one of claims 1 to 13, wherein the at least one storage space is substantially enclosed by a housing body and a lid, wherein the housing body and/or the lid are made predominantly of a polyvinylidene chloride (PVDC), a pharmaceutically compatible plastic coated completely or partially with PVDC, an olefin copolymer with heterocyclic side groups, or a polychlorotrifluoroethylene (PCTFE).
16. A pharmaceutical powder cartridge according to claim 15, wherein the at least one metering slide as a component of the metering device is made predominantly of a polyvinylidene chloride (PVDC), a pharmaceutically compatible plastic coated completely or partially with PVDC, an olefin copolymer with heterocyclic side groups, an at least partially oriented polypropylene (PP) or a polychlorotrifluoroethylene (PCTFE).
17. A pharmaceutical powder cartridge according to claim 15 or 16, wherein the housing body and/or lid comprises, on at least part of the side facing the storage space, a blend of desiccant embedded in a thermoplastic matrix.
18. A pharmaceutical powder cartridge according to claim 15, 16 or 17, containing at least one shaped body made of a blend of a thermoplastic matrix with a desiccant embedded therein.
19. A pharmaceutical powder cartridge according to claim 17 or 18, wherein channels are formed in a matrix of a thermoplastic of low water absorption, and are obtained by dissolving soluble co-extrudate components.
20. A pharmaceutical powder cartridge according to claim 17, 18 or 19, wherein fibres which absorb water vapour are embedded as filler in a matrix of a thermoplastic of low water absorption.
21. A pharmaceutical powder cartridge according to any one of claims 17 to 20, wherein the blend in a matrix of a thermoplastic of low water absorption and a desiccant embedded therein is designed at least as part of an inner wall of the at least one storage space by multi-component injection-moulding in a housing body made of a plastic substantially impermeable to water vapour.
22. A pharmaceutical powder cartridge according to any one of claims 15 to 21, wherein the housing body and lid together form a watertight seal.
23. A pharmaceutical powder cartridge according to claim 22, wherein the housing body and lid are sealed by ultrasonic welding.
24. A pharmaceutical powder cartridge according to any one of claims 15 to 23, wherein the seal is co-injected onto the housing body or the metering slide.
25. An inhaler for powdered pharmaceuticals, with a pharmaceutical powder cartridge as defined in any one of claims 1 to 24.
26. An inhaler for powdered pharmaceuticals, in which the pharmaceutical can be taken by a patient by way of an air stream, the inhaler comprising a holder for a pharmaceutical powder cartridge as defined in any one of claims 1 to 24.
27. A pharmaceutical powder cartridge according to any one of claims 1 to 24, containing a powder with one or more active substances comprising an analgesic, an anti-allergic, an antibiotic, an anti-cholinergic, an antihistamine, an anti-inflammatory substance, an antipyretic, a corticoid, a steroid, an antitussive, a bronchodilator, a diuretic, an enzyme, a substance acting on the cardiovascular system, a hormone, a protein or a peptide, or any combination thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10202940.07 | 2002-01-24 | ||
| DE10202940A DE10202940A1 (en) | 2002-01-24 | 2002-01-24 | Cartridge for a powder inhaler |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2415849A1 CA2415849A1 (en) | 2003-07-24 |
| CA2415849C true CA2415849C (en) | 2008-03-18 |
Family
ID=7713081
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002415849A Expired - Fee Related CA2415849C (en) | 2002-01-24 | 2003-01-08 | Pharmaceutical powder cartridge, and inhaler equipped with same |
Country Status (23)
| Country | Link |
|---|---|
| EP (2) | EP2286860A1 (en) |
| JP (1) | JP4597523B2 (en) |
| KR (2) | KR20110009727A (en) |
| CN (1) | CN100584402C (en) |
| AR (1) | AR038313A1 (en) |
| AT (1) | ATE509652T1 (en) |
| AU (1) | AU2003236784B2 (en) |
| BR (1) | BR0307094A (en) |
| CA (1) | CA2415849C (en) |
| DE (1) | DE10202940A1 (en) |
| ES (1) | ES2366683T3 (en) |
| HK (1) | HK1078809A1 (en) |
| HR (1) | HRP20040762A2 (en) |
| IL (1) | IL162996A (en) |
| MX (1) | MXPA04007197A (en) |
| NO (1) | NO20043324L (en) |
| NZ (1) | NZ534206A (en) |
| PL (1) | PL204871B1 (en) |
| RU (1) | RU2319512C2 (en) |
| TW (1) | TW575441B (en) |
| UA (1) | UA78746C2 (en) |
| WO (1) | WO2003061742A2 (en) |
| ZA (1) | ZA200405869B (en) |
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| ES2319596B1 (en) | 2006-12-22 | 2010-02-08 | Laboratorios Almirall S.A. | NEW DERIVATIVES OF THE AMINO-NICOTINIC AND AMINO-ISONICOTINIC ACIDS. |
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| UY31272A1 (en) | 2007-08-10 | 2009-01-30 | Almirall Lab | NEW DERIVATIVES OF AZABIFENILAMINOBENZOIC ACID |
| CA2716124A1 (en) * | 2008-02-20 | 2009-08-27 | Boehringer Ingelheim International Gmbh | Powder inhalers |
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2002
- 2002-01-24 DE DE10202940A patent/DE10202940A1/en not_active Withdrawn
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2003
- 2003-01-03 KR KR1020107029843A patent/KR20110009727A/en not_active Application Discontinuation
- 2003-01-03 CN CN03804167A patent/CN100584402C/en not_active Expired - Fee Related
- 2003-01-03 PL PL374327A patent/PL204871B1/en not_active IP Right Cessation
- 2003-01-03 EP EP10014581A patent/EP2286860A1/en not_active Withdrawn
- 2003-01-03 JP JP2003561682A patent/JP4597523B2/en not_active Expired - Fee Related
- 2003-01-03 AU AU2003236784A patent/AU2003236784B2/en not_active Ceased
- 2003-01-03 AT AT03731664T patent/ATE509652T1/en active
- 2003-01-03 BR BR0307094-8A patent/BR0307094A/en not_active IP Right Cessation
- 2003-01-03 RU RU2004126087/14A patent/RU2319512C2/en not_active IP Right Cessation
- 2003-01-03 ES ES03731664T patent/ES2366683T3/en not_active Expired - Lifetime
- 2003-01-03 MX MXPA04007197A patent/MXPA04007197A/en active IP Right Grant
- 2003-01-03 WO PCT/EP2003/000015 patent/WO2003061742A2/en active Application Filing
- 2003-01-03 EP EP03731664A patent/EP1469900B1/en not_active Expired - Lifetime
- 2003-01-03 KR KR10-2004-7011476A patent/KR20040096534A/en active IP Right Grant
- 2003-01-03 NZ NZ534206A patent/NZ534206A/en not_active IP Right Cessation
- 2003-01-08 CA CA002415849A patent/CA2415849C/en not_active Expired - Fee Related
- 2003-01-13 TW TW92100608A patent/TW575441B/en not_active IP Right Cessation
- 2003-01-23 AR ARP030100203A patent/AR038313A1/en active IP Right Grant
- 2003-03-01 UA UA20040706146A patent/UA78746C2/en unknown
-
2004
- 2004-07-13 IL IL162996A patent/IL162996A/en not_active IP Right Cessation
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- 2004-08-10 NO NO20043324A patent/NO20043324L/en not_active Application Discontinuation
- 2004-08-24 HR HR20040762A patent/HRP20040762A2/en not_active Application Discontinuation
-
2005
- 2005-11-25 HK HK05110703.2A patent/HK1078809A1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| ATE509652T1 (en) | 2011-06-15 |
| WO2003061742A3 (en) | 2003-12-31 |
| CN1642591A (en) | 2005-07-20 |
| DE10202940A1 (en) | 2003-07-31 |
| CN100584402C (en) | 2010-01-27 |
| ES2366683T3 (en) | 2011-10-24 |
| TW200302116A (en) | 2003-08-01 |
| WO2003061742A2 (en) | 2003-07-31 |
| EP1469900B1 (en) | 2011-05-18 |
| NO20043324L (en) | 2004-08-10 |
| KR20110009727A (en) | 2011-01-28 |
| BR0307094A (en) | 2005-03-01 |
| CA2415849A1 (en) | 2003-07-24 |
| EP2286860A1 (en) | 2011-02-23 |
| UA78746C2 (en) | 2007-04-25 |
| AU2003236784B2 (en) | 2008-01-24 |
| PL374327A1 (en) | 2005-10-17 |
| NZ534206A (en) | 2007-03-30 |
| IL162996A (en) | 2011-06-30 |
| HRP20040762A2 (en) | 2004-10-31 |
| JP2005515038A (en) | 2005-05-26 |
| HK1078809A1 (en) | 2006-03-24 |
| MXPA04007197A (en) | 2005-07-05 |
| ZA200405869B (en) | 2006-06-28 |
| KR20040096534A (en) | 2004-11-16 |
| WO2003061742A8 (en) | 2004-10-21 |
| JP4597523B2 (en) | 2010-12-15 |
| AR038313A1 (en) | 2005-01-12 |
| TW575441B (en) | 2004-02-11 |
| EP1469900A2 (en) | 2004-10-27 |
| RU2004126087A (en) | 2005-03-20 |
| PL204871B1 (en) | 2010-02-26 |
| RU2319512C2 (en) | 2008-03-20 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20130108 |