Classifications

• • 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
  • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
  • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
• • 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
  • A61M15/0021—Mouthpieces therefor
• • 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
  • A61M15/0021—Mouthpieces therefor
  • A61M15/0025—Mouthpieces therefor with caps
  • A61M15/0026—Hinged caps
• • 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
  • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
  • A61M15/003—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using capsules, e.g. to be perforated or broken-up
  • A61M15/0043—Non-destructive separation of the package, e.g. peeling
• • 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
  • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
  • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
  • A61M15/0046—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier
  • A61M15/0051—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type of carrier the dosages being arranged on a tape, e.g. strips
• • 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
  • A61M15/0028—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up
  • A61M15/0045—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters
  • A61M15/0053—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type or way of disposal
  • A61M15/0055—Inhalators using prepacked dosages, one for each application, e.g. capsules to be perforated or broken-up using multiple prepacked dosages on a same carrier, e.g. blisters characterized by the type or way of disposal the used dosages being coiled
• • 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
  • A61M15/0075—Mechanical counters having a display or indicator on a disc
• • 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
  • A61M15/0081—Locking means
• • 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
  • A61M2202/062—Desiccants
• • 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
• • 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
  • A61M2205/00—General characteristics of the apparatus
  • A61M2205/27—General characteristics of the apparatus preventing use
  • A61M2205/276—General characteristics of the apparatus preventing use preventing unwanted use
• • 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
  • A61M2206/00—Characteristics of a physical parameter; associated device therefor
  • A61M2206/10—Flow characteristics
  • A61M2206/16—Rotating swirling helical flow, e.g. by tangential inflows

Definitions

• the present invention relates to an inhaler appropriate for delivering the medicament in dry powder form used in the treatment of respiratory diseases, particularly in asthma and chronic obstructive pulmonary disease (COPD).
• COPD chronic obstructive pulmonary disease
• the present invention relates to an inhaler which comprises blister package appropriate for carrying medicament in dry powder form and is used so as to achieve an effective inhalation.
• inhalers for delivering medicaments utilized in the treatment and prophylaxis of respiratory diseases by the oral route.
• Inhalation treatment is the most commonly preferred treatment method in these diseases as the inhalers provide ease of use; the medicaments have rapider onset of time resulting from local administration and they have fewer side effects.
• Various inhalers have been designed in order to provide effective and sufficient delivery of the medicaments used in the treatment of respiratory diseases, particularly in asthma and chronic obstructive pulmonary disease. These inhalers vary according to their operating mechanisms and the physical form of the medicament to be delivered.
• the medicament is carried in reservoirs, capsules or blisters packages. It is highly significant to provide the delivery of sufficient amounts of the medicament to the patient since the required amount of the dry powder medicament to be delivered to the patient for each inhalation is very low.
• one blister pocket is opened in response to each actuation of the dry powder inhalers comprising blister packages and one dose of dry powder medicament contained in the pocket is inhaled upon the respiration of the patient.
• the active agents used in inhalation treatment have quite strong effects, the amount of active agent comprised in a dry powder medicament is rather low. Therefore, it is essential that the required amount of active agent for an effective inhalation is absorbed in the lungs of the patient because absorption of less than the required amount of active agent is insufficient for an effective inhalation.
• the medicament in dry powder form has to have the appropriate particle size distribution for the required amount of the active agent comprised by the dry powder medicament in the opened blister to be able to reach the lungs.
• the particles having a particle size larger than 20 ⁇ accumulate in oral cavity and throat of the patient while the particles having a smaller particle size than 1 ⁇ adheres to esophagus or exits the body via the respiration of the patient.
• the particle size of the particles absorbed by the alveolus in the lungs is in the range of 1 ⁇ to 5 ⁇ .
• the particle size of the active agent has to be in the range of 1 ⁇ to 5 ⁇ in order to enable the absorption of the active agent comprised in the dry powder medicament by the alveolus in the lungs.
• the blister opened in response to each actuation of the inhaler has a high discharge capacity for the required amount of the active agent to be inhaled.
• Blister's having a high discharge capacity refers that almost the entire dry powder medicament contained in the blister pocket is discharged during the inhalation. To this end, the inhaler should hold the specifications that enable the inhalation of the dry powder medicament in each opened blister pocket with high discharge capacity.
• Diskus® The inhalation device marketed under the trade mark Diskus® by GlaxoSmithKlein is one of the most well-known dry powder inhalers on the market. This device comprises a blister strip package in which the dry powder medicament is carried and operates with a slide mechanism.
• Diskus® inhaler remains incapable to achieve an effective inhalation as it does not hold any specifications that can eliminate or prevent the problems mentioned above.
• the present invention relates to an inhaler which enables the inhalation of the active agent comprised in the dry powder medicament stored in each blister pocket of the blister pack at an appropriate particle size so as to achieve an effective inhalation, and the absorption of required amount of the active agent from the patient's lungs.
• the present invention relates to an inhaler provides the blister pockets each of which contains medicament in dry powder form to have high discharge capacity so as to enable the delivery of required amount of the active agent to the patient.
• An inhaler suitable for delivery of the medicament in dry powder form according to the present invention comprising;
• a blister package composed of a plurality of blister pockets each of which comprises medicament in dry powder form and which are spaced at equal intervals;
• a mouthpiece enabling the patient to inhale the medicament in dry powder form from the opened blister ;
• a manifold through which the air entering from the air inlet passes is characterized in the apertures on the opposite walls in the second part of the manifold that is partitioned off from the first part of the two-part manifold where the air entering the device through at least one air inlet upon the inhalation of the patient entrains the dry powder medicament in the blister in order to create turbulence.
• the inhaler pertaining to the present invention is preferably actuated by the rotation of the mouthpiece cover in terms of providing ease of use to the patients.
• the patient For the dry powder medicament prepared for inhalation upon the rotation of the mouthpiece cover to be inhaled, the patient should seal his oral cavity on the mouthpiece and breathe in. While the patient breathes in, the external air enters the manifold passing through the air inlet.
• the inhaler is an easy-grip, manual device which is appropriate for delivering medicament in dry powder form.
• the housing of the device pertaining to the present invention has been designed such that each component of the blister package and the gear mechanism which have a significant role in enabling the device to work properly is situated accurately and works harmoniously.
• the housing is divided into several compartments.
• the used portion and the unused portion of the blister package are accommodated in separated compartments in order to prevent the medicament in dry powder form remained in the opened blister pocket to spill on the other components of the housing.
• the housing also comprise the beak which enables the blister package to be peeled and the manifold through which the dry powder medicament in the open blister passes before reaching the mouthpiece during the inhalation.
• the housing can be in any appropriate shape while it is preferably elliptic or circular.
• the upper and the lower housing members interlock with each other and enclose the housing in order to keep the housing and the gear mechanism fixed together.
• the mouthpiece cover hiding the mouthpiece is rotated by being slid on the upper and lower housing members.
• the grids on the surface of the lower and the upper housing members provide an effective actuation by preventing the slipping of the finger while rotating the mouthpiece cover.
• the upper and the lower housing members can be in any appropriate shape or size which provides ease of use.
• the mouthpiece cover hiding the mouthpiece of the device pertaining to the present invention has been designed such that it also provides to actuate the device.
• both the mouthpiece is uncovered and one dose of the medicament in dry powder becomes ready for inhalation as one of the blister pockets is opened as a result of the mouthpiece cover's preferably being manually rotated along the path restricted by the engagement of the protrusions on the upper and the lower housing members.
• the rotational path on which the cover moves is restricted on both ends by the protrusions of the upper and the lower housing members.
• the constant-distance path that the protrusions of the upper and the lower housing members define results in the mouthpiece cover's being rotated by the same angle in response to the each actuation of the device.
• the mouthpiece cover that actuates the device can solely be in two positions. Holding the carved part on one end, the mouthpiece cover can be easily shifted from the first position to the second position. The mouthpiece is completely hidden when the mouthpiece cover is in the first position and the device is on standby mode. When the mouthpiece cover is in the second position, the mouthpiece is completely exposed and one dose of the medicament in dry powder form is prepared for inhalation upon the actuation of the device.
• the mouthpiece cover of the device is joined with the gear mechanism by the connection points.
• One end of the drive gear passes through the center of the lower housing member and tightly joins with the mouthpiece cover in one connection point while the other end passes through the center of the upper housing member and tightly joins with the mouthpiece cover in the other connection point.
• one side cover is used for each end of the drive gear.
• the ends of the drive gear are carved for the ends of the side covers to be joined with each end of the drive gear from inside such that the ends of the side covers can tightly interlock with it. Inner faces of these carved parts in each end of the drive gear have a matching shape with the shapes of the ends of the side covers.
• connection point On each connection point of the mouthpiece cover, there is a stabilizing resilient cover.
• the extensions under the stabilizing resilient covers pass through the holes on the upper or the lower housing member according to the position of the connection point and provide the stabilizing resilient covers that they connect with to remain stable.
• the rotation of the mouthpiece cover is prevented from both sides as the pawl under each of the stabilizing resilient covers in both sides of the device interlocks with the mouthpiece cover.
• the resilient parts of each stabilizing resilient cover which are compatible with the shape of the fingers are pressed on for raising the pawls and releasing the mouthpiece cover in order to move the mouthpiece cover which actuates the device.
• the mouthpiece cover can easily be rotated when the resilient parts of each stabilizing resilient cover on both sides of the device which match with the shape of the fingers are pressed on.
• the resilient parts of the stabilizing resilient covers are not pressed on, the pawls under the stabilizing resilient covers do not allow the mouthpiece cover to move in any circumstances.
• the mouthpiece cover that actuates the device can solely be in two positions. When the mouthpiece cover is in the first position, it leans on the protruding part in one end of the rotational path. The mouthpiece is completely hidden when the mouthpiece cover is in the first position and the device is on standby mode. When the mouthpiece cover is in the second position, it leans on the protruding part on the other end of the rotational path and one dose of the medicament in dry powder form is prepared for inhalation upon the actuation of the device.
• Each gear of the gear mechanism in the device according to the present invention is directly or indirectly engages with each other.
• the drive gear which is one of the components of the gear mechanism, provides the mouthpiece cover to trigger the gear mechanism.
• the constant-angle rotational movement of the cover is transmitted by the indexing ratchet wheel which interlocks with the indexing wheel via the drive gear.
• the indexing wheel that synchronizes with the indexing ratchet wheel is engaged with the winding wheel gear and the pinion gear and causes them to move as well.
• both the lid sheet of the blister package is provided to be coiled on the wings of the winding wheel as the winding wheel is rotated by the mechanism gear that engages with the winding wheel gear, and the counter gear that engages with the small gear under the base gear is provided to be rotated by means of the base gear that engages with the pinion gear.
• the indexing wheel is another component of the gear mechanism and it provides the blister package to be indexed properly and the opened blisters to be positioned accurately.
• the recesses of the indexing wheel match with the shape of the blister package and the blister pockets of the blister package are received in these recesses in sequence while the indexing wheel rotates. There are preferably 8 recesses on the indexing wheel.
• the indexing wheel is supposed to rotate by the same angle in response to each actuation of the device for the opened blister pocket to be positioned accurately.
• the angle between each recess is equal and 45°.
• the indexing wheel has to rotate by the same angle each time. As the indexing wheel rotates by the same angle, the blister package is indexed to the same extent and the opened blister pocket is provided to be accurately positioned.
• At least one stopper component is arranged in any suitable part of the device in order to provide the blister package to be precisely positioned.
• the stopper can be in any suitable shape to execute said task.
• the counter gear in the device pertaining to the present invention displays the number of the unused blister pockets remained in the device.
• the mouthpiece is uncovered, the blister package is indexed and one dose of the dry powder medicament is prepared for inhalation while the counter gear rotates as well.
• the movement of the mouthpiece cover causes the mouthpiece cover to be uncovered; one dose of the dry powder medicament to be ready for inhalation after the blister pocket is opened as well as providing the counter gear to rotate and display the new value of the unused blister pockets remained.
• the counter gear On the counter gear, there exist numerals equal to the number of the blister pockets present in the device and they are spaced by equal angles. In a device comprising 60 doses, the angle between the numerals is approximately 5°.
• the counter gear rotates as a result of the reflection of the rotation of the indexing wheel via the pinion gear and the base gear.
• rotation of the indexing wheel by the same angle each time due to the accurate transmission of the movement of the mouthpiece to the gear mechanism via the drive gear results in the rotation of the counter wheel approximately by the same angle as well and each numeral on the counter wheel is clearly seen through the display aperture on the upper housing member. Therefore, the patient makes sure about the number of the unused blister pockets remained in the device.
• the device Before the inhalation, the device is actuated by pressing on the stabilizing resilient covers on both faces of the device and rotating the mouthpiece cover along the rotational path, and the drive gear which is joined with the both connection points of the mouthpiece cover via the side covers precisely transmits the movement of the mouthpiece cover to the indexing ratchet wheel owing to the side covers upon the actuation of the device.
• the indexing ratchet wheel interlocks with the indexing wheel from inside thanks to its arms and enables the indexing wheel to rotate 45°.
• the blister package indexed and it is peeled by means of the beak present in the housing. As the indexing wheel engages with the winding wheel gear and the pinion gear, these gears synchronize with the indexing wheel.
• the mechanism gear engages both with the winding wheel gear and the winding wheel, the rotation of the winding wheel gear causes the winding wheel to move and lid sheet of the blister package coils on the winding wheel tightly.
• the pinion gear engages with the base gear while the small gear under the base gear engages with the counter gear.
• the movement of the mouthpiece cover along the rotational path causes the blister package to be accurately positioned as a result of the rotation of the indexing wheel by 45 degrees and the number of the unused blisters remained in the device is clearly seen through the display aperture as the counter gear rotates approximately by 5 degrees.
• the inhaler according to any of the proceeding claims, further comprising a blister package composed of a plurality of blister pockets each of which comprises medicament in dry powder form and which are spaced at equal intervals.
• the blister package carries the medicament in dry powder form in one-dose portions and it is preferably a blister strip and it is preferably peelable.
• the blister pockets comprised in the blister package are spaced in equal intervals and each of them carries one dose of the medicament in dry powder form.
• the base sheet of the blister package on which the blister cavities are spaced is accumulated in the separated compartment of the housing.
• the lid sheet that provides impermeability of the blister package on the other hand, is coiled on the winding wheel which is one of the components of the gear mechanism positioned in the other side of the housing.
• the blister opened by the beak is situated immediately under the manifold.
• the airflow that preferably enters the device through at least one air inlet on the upper housing member entrains the dry powder medicament in the opened blister pocket via the manifold to the mouthpiece and enables the delivery of said medicament to the patient.
• the air inlet on the upper housing member that allows the entry of air can be in any suitable shape and size that also enable external air to enter the device easily and at a convenient speed.
• the mouthpiece is designed to fit the mouth for the patient to comfortably inhale the medicament in dry powder form.
• the mouthpiece can be in any suitable shape or size as well as being fixed or movable. Furthermore, it can be attached or unattached to the upper and/or the lower cover.
• the air inlet that the external airflow passes through is preferably designed not to be close where the patient holds the device in order not to prevent the air flow. Furthermore, in order to deliver the required amount of the dry powder medicament in the opened blister to the patient, the air inlet has been designed such that it allows the entry of the airflow through the air inlet by a convenient angle.
• the manifold between the opened blister and the mouthpiece When the manifold between the opened blister and the mouthpiece is considered as a whole, one end of its communicates with the opened blister while the other end communicates with the mouthpiece.
• the manifold is connected to the mouthpiece by the tapered channel.
• the external air passes through the air aperture and reaches the manifold.
• the dry powder medicament is inhaled at the appropriate particle size distribution as a result of the dispersion of the agglomeration in the dry powder medicament entrained to the second part of the manifold.
• the medicament in dry powder form entrained to the second part of the manifold is delivered to the patient via the mouthpiece.
• the manifold can be in appropriate shape while the distance between the end of the manifold communicating with the mouthpiece and the end of its communicating with the blister is at least 1 mm.
• each aperture on each of the opposite walls in the second part of the manifold there can be at least one aperture on each of the opposite walls in the second part of the manifold.
• One of the said walls in the second part of the manifold is the one partitioning the manifold into two parts and lying between the apertures with four sub-apertures.
• These apertures can be in any appropriate shape and their cross-sections can be equal or different. However, the cross-sections of these apertures are preferably different to provide the airflows passing through these apertures to be at different speed.
• the cross-section of each aperture is in the range of 0,01 mm 2 to 27 mm 2 , preferably in the range of 0,01 mm 2 to 17 mm 2 , more preferably in the range of 0,01 mm to 7 mm .
• the said apertures can be positioned exactly opposite or asymmetrically on the appropriate spots of the walls.
• the air apertures with four sub-apertures on the edge of the manifold that is close to the blister are preferably shaped circular.
• the distance between the centers of these apertures is one of the factors affecting the discharge capacity of the opened blister because accurate positioning of these air apertures causes the sufficient amount of the external air to enter into the opened blister and entrain the entire dry powder medicament in the blister from the blister to the manifold.
• the distance between the centers of the two apertures with four sub-apertures in the inhaler is in the range of 3,0 mm to 3,8 mm, more preferably in the range of 3,2 mm to 3,6 mm.
• an effective inhalation used throughout the text refers to the desired result which is induced as a result of the delivery of the active agent in quantities required for inhalation treatment to the patient's lungs.
• Each component of the device pertaining to the present invention can be made of any appropriate substance while it is preferably made of plastics.
• plastics are selected from a group comprising styrene-acrylonitrile, polyoxymethylene, acrylic- polymethylmetacrylate, cellulose acetate, polyetheretherketone, polyvinyl choloride, polyethylene, polypropylene, acrylonitrile butadiene styrene, polycarbonate, polyamide, polystyrene, polyurathane or fluoropolymer types while it is more preferably polyoxymethylene.
• the components made of plastics can be produced by methods such as injection molding.
• each component of the device can be in any appropriate color.
• the lid and the base sheets constituting the blister package preferably consist of a plurality of layers.
• Each of these layers are preferably chosen from a group comprising polymeric layers that are made of various polymeric substances; aluminum foil and fluoropolymer film.
• the lid and base sheets composing the blister package are sealed very tightly by at least one of the methods comprising cold formed bonding, hot metal bonding, hot metal welding, radio frequency welding, laser welding or ultrasonic welding in order to provide impermeability, more preferably by cold formed bonding method. Since these cold formed bonding methods can be carried out at lower temperatures than hot sealing methods, they are the most appropriate methods to use in the case that the medicament carried in the blister is heat sensitive.
• Fluoropolymer film is a polymeric film which is used in blister packs and provides excellent moisture barrier. This chemically inert polymeric film does not cause any change in the taste of the formulation when it is in contact with the dry powder formulation. In addition, it easily constitutes a layered structure with the other polymeric layers which are composed of various polymers. It is appropriate to be transacted with heat.
• At least one of the polymeric layers comprises at least one desiccant agent including silica gel, zeolite, alumina, bauxite, anhydrous calcium sulfate, activated carbon and clay which has the property of water absorption in order to decrease gas and moisture permeability of the layer.
• desiccant agent including silica gel, zeolite, alumina, bauxite, anhydrous calcium sulfate, activated carbon and clay which has the property of water absorption in order to decrease gas and moisture permeability of the layer.
• the thickness of the aluminum foil in the lid and the base sheets of the blister package are preferably chosen to be in the range of 5 to 80 ⁇ , more preferably in the range of 15 to 65 ⁇ .
• the polymeric layers in the lid and the base sheets of the blister pack are made of the same or different polymers.
• the thickness of these polymeric layers varies according to the type of the polymeric substance used and its properties while they are preferably in the range of 5 to 100 ⁇ , more preferably in the range of 15 to 60 ⁇ .
• the polymers composing the polymeric layer are preferably selected from thermoplastics such as polyethylene, polypropylene, polystyrene, polyolefin, polyamide, polyvinyl chloride, polyurethane or synthetic polymers.
• the blister pockets in the blister package can be in any appropriate shape.
• the plurality of blister pockets spaced at equal intervals on the base sheet of the blister package can be in the same or different shape, structure or volume.
• Figure 1 is a perspective view of an inhaler according to the inhaler described in the present invention.
• Figure 2 is an exploded view of the inhaler pertaining to the invention
• Figure 3 is a perspective view of the blister pack for use with the inhaler pertaining to the invention.
• Figures 4a and 4b are perspective views of the housing of the inhaler according to the invention.
• Figures 4c is a perspective view of the housing of the inhaler according to the invention.
• Figures 4d and 4e are cross-sectional views of the manifold part of the inhaler pertaining to the invention which is shown as X in figure 4c;
• FIGS. 5 a and 5b are perspective views of upper and lower housing members of the inhaler according to the invention.
• Figure 6a is a perspective view of the mouthpiece cover of the inhaler pertaining to the invention.
• Figure 6b is an exploded view of the communication between the mouthpiece cover, the drive gear and the stabilizing resilient covers in the inhaler pertaining to the invention
• Figure 6c is a cross-sectional view of the communication between the mouthpiece cover, the drive gear and the stabilizing resilient covers in the inhaler pertaining to the invention
• Figure 6d is a cross-sectional view of the communication between the mouthpiece cover, the drive gear and the stabilizing resilient covers in the inhaler pertaining to the invention
• Figure 6e is an exploded view of the communication between the drive gear and the side covers in the inhaler pertaining to the invention.
• Figure 6f is a cross-sectional view of the connection of the stabilizing resilient cover with the lower housing member in the inhaler pertaining to the invention.
• Figures 7a- 7c are cross-sectional views of the engagement of the gears composing the gear mechanism with each other in the inhaler pertaining to the present invention.
• Figure 8 is a cross-sectional view of the blister package delaminating in course of operation of the inhaler pertaining to the present invention.
• Figure 9 is a perspective view of the counter gear used in the inhaler pertaining to the present invention.
• the inhaler (1) pertaining to the present invention comprises a gear mechanism situated in the housing (10) between the upper housing member (4a) and the lower housing member (4b) in order to enable the inhalation of the dry powder medicament carried in a blister package (15) as displayed in figures 1 and 2.
• Each component of the inhaler (1) is positioned at appropriate spots of the device to guarantee their working properly and accurately.
• the inhaler (1) pertaining to the present invention shown in figure 1 is ready for inhalation.
• the mouthpiece cover (2) is in the second position and the mouthpiece (14) is entirely exposed.
• Rotating by holding on the carved part (2a) on one end the mouthpiece cover (2) is switched to the second position from the first position wherein the mouthpiece is completely covered.
• the mouthpiece (14) is completely exposed when the mouthpiece cover (2) is switched to the second position from the first position and the gear mechanism is triggered by the drive gear (12).
• the drive gear (12) precisely transmits the movement of the mouthpiece cover (2) to the indexing ratchet wheel (3).
• the indexing wheel (8) which engages with the indexing ratchet wheel (3) enables the blister package (15) shown in figure 3 to be indexed.
• the blister pockets (15a) composing the blister package are received in the recesses (8a) on the indexing wheel and the blister package (15) is indexed when the indexing wheel (8) rotates.
• shapes of the recesses (8a) on the indexing wheel (8) have been designed to match the shapes of the blister pockets (15) composing the blister package (15) for the blister package to be indexed properly.
• the blister package (15) shown in figure 3 is composed of the lid sheet (15b) which provides impermeability and the base sheet (15c) on which the blister pockets (15a) are spaced at equal intervals.
• Each blister pocket contains medicament in dry powder form comprising one or more active agents.
• the rotational movement that the mouthpiece cover (2) of the device executes while switching from the first position to the second is transmitted to the indexing ratchet wheel (3) via the drive gear (12) that the mouthpiece cover (2) engages with.
• arms (3a) of the indexing ratchet wheel interlocks with protrusions inside the indexing wheel (8) and rotates the indexing wheel (8) unidirectionally. Therefore, the blister package (15) is indexed forward while the indexing wheel (8a) rotates as the blister pockets (15a) composing the blister package (15) are received in the recesses (8a) of the indexing wheel.
• the beak (16) in the housing (10) provides the blister package (15) to be peeled while the blister package (15) is indexed and provides one blister pocket (15a) to be opened in response to each actuation of the device (1).
• the winding wheel gear (6) which is another component of the gear mechanism, engages with the indexing wheel (8) as displayed in figure 2.
• the mechanism gear (5) that interlocks with the winding wheel (13) from inside has arms (5a) to interlock with the interior teeth of the winding wheel gear (6).
• the indexing wheel (12) rotates the winding wheel gear (6)
• the winding wheel rotates unidirectionally owing to the arms of the mechanism gear (5a) which interlock with the interior teeth of the winding wheel gear (6) and the lid sheet (15b) which is peeled away while the blister package is indexed is tightly coiled on the wings (13a) of the winding wheel.
• the base sheet (15c) of the blister package (15) where the blister pockets are spaced is accumulated in a separate part (18a) of the device.
• FIG. 10 Different perspective views of the housing (10) wherein the gear mechanism and the other components of the inhaler (1) pertaining to the present invention are arranged are displayed in figures 4a and 4b. Furthermore, as can be seen in figures 4a and 4b, the housing (10) also comprises the other components having significant roles in the actuation of the device such as the beak (16), the manifold (20), the apertures with four sub-apertures (20a, 20b). Each component comprised in the housing is situated in appropriate parts of the housing (10) in order to enable the inhaler (1) to work properly.
• the drive gear (12) passes through the center (21) of the housing and joins the mouthpiece cover (2) at two points.
• the blister package (15) is in the lower part (17) of the housing as coiled up.
• the blister package (15) is peeled by the beak (16) in the housing while being indexed by the indexing wheel (8) situated in the upper part (19) of the housing.
• the lid sheet (15b) of the blister package (15) which provides impermeability is indexed over the beak (16) and coiled on the winding wheel (13) which is situated in the side part (18) of the housing.
• the air passes through the air inlet with four sub-apertures (20a) under the manifold (20) into the opened blister pocket; entrains the dry powder medicament contained in the opened blister pocket (15a) in response to each actuation of the device; provides it to pass through the other aperture with four-sub-apertures (20b) and reach the mouthpiece via the manifold (20).
• a view of the cross-section of the housing component (10) which illustrated as X in figure 4c and includes the manifold part (20) is given in figures 4d and 4e. According to figure 4d, the blister pocket (15a) opened upon the actuation of the inhaler (1) is positioned immediately under the apertures with four sub-apertures (20a, 20b).
• Some part of the external air which runs through the air inlet (22) and enters the inhaler (1) upon the patient's breathing in passes through the first part (20c) of the manifold and reaches the opened blister pocket (15a) while the rest passes through the aperture (20e) on wall A and the aperture (20f) on wall B and enters the second part (20d) of the manifold.
• the apertures (20e; 20f) on wall A and wall B are asymmetrically positioned. Shapes and the cross-sections of the apertures (20e; 20f) on wall A and wall B can be identical or different.
• an effective turbulence is created in the second part (20d) of the manifold as the speed of the airflow entering through the aperture (20e) on wall A and the speed of the airflow entering through the aperture (20f) on wall B are different.
• the created turbulence disperse the agglomeration of the dry powder medicament entrained to the second part (20d) of the manifold and provides the dry powder medicament to be delivered to the patient at appropriate particle size distribution.
• FIG. 4e Another cross-sectional view of the part of the housing which is shown as X in figure 4c is given in figure 4e.
• FIG. 4e In the cross-sectional view of the manifold illustrated in figure 4e, there are two apertures (20f; 20g) on wall B of the manifold differently from figure 4d.
• the apertures (20e; 20f) on wall A and wall B are asymmetrically positioned with respect to each other.
• the shapes and the cross-sections of the apertures (20e; 20f; 20f) on wall A and wall B which allow the air in the second part (20d) of the manifold can be identical or different.
• the airflow entering in through the aperture (20e) on wall A and the airflows entering in through the apertures (20f; 20g) on wall B create an effective turbulence in the second part (20d) of the manifold.
• This turbulence disperses the agglomeration in the dry powder medicament entrained to the second part (20d) of the manifold and enables the medicament in dry powder form to be delivered to the patient at an appropriate particle size distribution.
• the housing (10) and the other components of the inhaler (1) pertaining to the present invention are stably kept together as the upper housing member (4a) and the lower housing member (4b) displayed in figures 5a and 5b are joined together.
• the engagement tabs (28) on the inside surface of the lower housing member (4b) engage with the engagement recesses (27) on the inside surface of the upper housing member (4a) and the upper and lower housing members are fixed tightly. Therefore, the protrusions (23a, 23b) on the upper housing member (4a) and the protrusions (24a, 24b) on the lower housing member (4b) are joined end to end and they define the restricted path for the rotational movement of the mouthpiece cover (2).
• the mouthpiece cover (2) can be moved along this path.
• the mouthpiece cover (2) When the mouthpiece cover (2) is in the first position, the mouthpiece is completely covered, the device is in standby mode and the mouthpiece cover (2) leans on the first protrusion (23 a) on the upper housing member and the first protrusion (24a) on the lower housing member.
• the mouthpiece (2) is manually slid along the rotational path with the help of the carved part to switch to the second position.
• the mouthpiece is completely exposed when the cover is in this position, one dose of the dry powder medicament is ready for inhalation and the mouthpiece cover (2) leans on the second protrusion (23b) on the upper housing member and the second protrusion (24b) on the lower housing member.
• one half (25a) of the tapered channel that interconnects the manifold (20) that exist in the housing (10) with the mouthpiece (14) is comprised in the upper housing member (4a) while the other half of it (25b) is comprised in the lower housing member (4b).
• the channel is constituted as a whole when the upper (4a) and the lower (4b) housing members are joined together.
• the air that enters the device through the air inlet (22) arranged in the upper housing member (4a) passes through the aperture with four sub-apertures (20a), reaches the opened blister (15a) and entrains the dry powder medicament there to the manifold (20) by passing it through the other aperture with four sub-apertures (20b).
• the grids on the upper housing member (23e, 23f) and the grids on the lower housing member (24e, 24f) prevent the slips of fingers when rotating the mouthpiece cover.
• the mouthpiece cover (2) of the inhaler pertaining to the present invention is displayed in figure 6a.
• the carved part (2a) in one end of the device enables to easily move the mouthpiece cover manually.
• the mouthpiece cover (2) is joined with the gear mechanism via the connection points.
• the drive gear (12) is joined with the connection points (29, 30) of the mouthpiece cover via the side covers (31a, 31c) as it can clearly be seen in figures 6b, 6c and 6d illustrating the communication between the mouthpiece cover (2), the drive gear (12), side covers (31a, 31c) and the stabilizing resilient covers (32,33).
• Each of these side covers (31a; 31c) passes through the center (4d) of the upper housing member or the center (4e) of the lower housing member and joins with the end (12a; 12b) of the drive gear. It can clearly be seen in figure 6d that the both ends (12a; 12b) of the drive gear is carved such that the end of the side cover (31b; 3 Id) can pass through.
• Each end of the side covers (3 Id; 31b) passes through one of the connection points (29; 30) of the mouthpiece cover and it is received in the recess in one end (12b; 12a) of the drive gear, thus it provides to tightly and stably interconnect the mouthpiece cover (2) with the drive gear (12).
• the mouthpiece cover (2) synchronizes with the drive gear (12) as the connection point (29; 30) of the mouthpiece cover which has a matching shape with the ends (3 Id; 31b) of the side covers that passes through it on both sides of the device and the end (12b; 12d) of the drive gear that it communicates with are on the same component.
• the shapes of the ends (31b; 3 Id) of the side covers that are received in the carved parts on the ends of the drive gear and the shapes of the connection points (29, 30) of the mouthpiece cover are not identical since the two ends (12a, 12b) of the drive gear are not identical.
• stabilizing resilient cover (33; 32) on each connection point (29; 30) of the mouthpiece and on each side cover (31c; 31a), as displayed in figures 2, 6a-6d and 6f.
• the pawls (32a, 33a) under the stabilizing resilient covers which are on the connection points (29, 30) of the mouthpiece, interlock with the mouthpiece cover (2) on both sides as clearly seen in figures 6c and 6d.
• the pawl (33 a) under the stabilizing resilient cover that is on the first connection point (29) interlocks with the mouthpiece cover on one side (figure 6c).
• the pawl (32a) under the stabilizing resilient cover that is on the second connection point (30) of the mouthpiece cover interlocks with the mouthpiece cover (2) on the other side (figure 6d).
• the pawls (32a, 33a) under the stabilizing resilient covers interlock with the mouthpiece cover (2) on both sides and prevent its rotation, and therefore the inadvertent actuation of the gear mechanism.
• the extensions (32b, 32c; 33b, 33c) under the stabilizing resilient covers pass through the apertures (23 c, 23 d; 24c, 24d) on the upper and the lower housing members illustrated in figures 5a and 5b and provide the stabilizing resilient covers to remain stable.
• the extensions (33b; 33c) under the stabilizing resilient cover that is on the first connection point (29) of the mouthpiece cover pass through the apertures (23c; 23d) on the upper housing member and provide the stabilizing resilient cover (33) to be stably joined with the device.
• the extensions (32b, 32c) under the stabilizing resilient cover on the second connection point (30) of the mouthpiece cover pass through the apertures (24c, 24d) on the lower housing member and provide the stabilizing resilient cover (32) to be stably joined with the device as clearly illustrated in figure 6f.
• each stabilizing resilient cover illustrated in figures 6c and 6d Before the inhalation, the resilient parts (32d, 33 d) of each stabilizing resilient cover illustrated in figures 6c and 6d are pressed on for raising the pawls (32a, 33a) and releasing the mouthpiece cover (2) in order to actuate the gear mechanism of the device to prepare one dose of dry powder medicament before inhalation. Therefore, the gear mechanism of the device is actuated and one blister pocket (15a) is opened for one dose of the dry powder medicament to be ready for inhalation when the resilient parts (32d, 33d) of the stabilizing resilient covers are pressed on and the mouthpiece cover (2) is switched from the first position to the second position simultaneously.
• the necessity to press on the resilient parts (32d, 33 d) of the stabilizing resilient covers so as to actuate the gear mechanism preclude the consequences which may result from accidental and inadvertent actuations of the gear mechanism.
• FIG 7a it is displayed that the stopper (26) interlocks with the tooth of the indexing ratchet wheel (3) and hinders its rotation.
• the rotational movement of the mouthpiece cover (2) by the same angle in response to each actuation of the device (1) is accurately transmitted to the indexing ratchet wheel (3) by the drive gear (12) which engages with the mouthpiece cover (2) on its both ends and the drive gear (12) is enabled to rotate by the same angle in each actuation of the device (1).
• the stopper component (26) in the lower housing member (4b) prevents the backwards movement of the blister package (15) indexed by the indexing wheel (8) which synchronizes with the indexing ratchet wheel by keeping the position of the indexing ratchet wheel (3) fixed and provides the blister package (15) to be precisely positioned.
• the lid sheet (15b) of the blister package (15) which is peeled away by the beak (16) and the base sheet (15c) are enclosed in separate compartments.
• the lid sheet (15b) that provides impermeability is indexed over the beak (16) and tightly coiled on the wings (13a) of the winding wheel.
• the base sheet (15c) of the blister package (15) where the blister pockets (15a) each of which carries one dose of the dry powder medicament are spaced is accumulated in the separated compartment (18a) of the housing (10).
• one dose of the dry powder medicament which is prepared for inhalation after one blister pocket (15a) is opened and the air entering the device through the air inlet (22) upon the inhalation of the patient provides to deliver one dose of the dry powder medicament to the patient by entraining it from the blister pocket (15a) to the mouthpiece (14).
• the rotation of the indexing wheel (8) is transmitted to the base gear (7) engaging with the pinion gear (11) by the pinion gear (11).
• the small gear which is under the base gear (7) as attached to it engages with the counter gear (9) (figure 7c).
• the movement of the indexing wheel (8) is transmitted to the counter wheel (9) shown in figure 9 by the pinion gear (11) and the base gear.
• the counter gear rotates approximately 5° and the number of the unused blister pockets remained in the device are clearly seen through the display aperture (4c) on the lower housing member (4b).
• the mouthpiece (14) is exposed when the mouthpiece cover (2) is slid from the first position to the second on the upper housing member (4a) and the lower housing member (4b); the gear mechanism is triggered by the drive gear (12) and one dose of dry powder medicament is prepared for inhalation; the counter gear (9) is indexed and the numeral seen through the display aperture (4c) on the lower housing member (4b) is incremented.
• the mouthpiece cover (2) is solely moved from the second position to the first position wherein the mouthpiece (14) is completely covered.
• the medicament in dry powder form which is stored in blister cavities is manufactured according to the prior art.
• the particle sizes of the active agents comprised in the dry powder medicament are smaller than 20 ⁇ , preferably smaller than 10 ⁇ .
• the inhaler pertaining to the present invention has been designed so as to deliver the dry powder medicament used in monotherapy or combined therapy.
• monotherapy refers to inhalation treatments in which dry powder medicaments comprising a single active agent are used whereas the term “combined therapy” refers to inhalation treatments in which dry powder medicaments comprising more than one active agents are use used.
• the dry powder medicament delivered via the device pertaining to the present invention comprises at least one excipient in addition to the active agent or agents.
• excipients are generally chosen from a group comprising monosaccharides (glucose, arabinose, etc.), disaccharides (lactose, saccharose, maltose, etc.), oligo- and polysaccharides (dextran, etc.), polyalcohols (sorbite, mannite, xylite), salts (sodium chloride, calcium carbonate, etc.) or combinations thereof.
• the medicament in dry powder form comprises lactose as the excipient.
• the medicament in dry powder form comprises fine or coarse excipients particles preferably having various particle size ranges in order to deliver the required amount to the lungs.
• the active agent or the active agents comprised in the dry powder medicament which is stored in blister packages used in the device pertaining to the present invention can be selected from a group comprising cromolyns, anti-infectives, antihistamines, steroids, antiinflammatories, bronchodilators, leukotirene inhibitors, PDE IV inhibitors, antitussives, diuretics, anticholinergics, hormones, xanthines and pharmaceutically acceptable combinations thereof.
• the active agent comprised in the medicament in dry powder form delivered via the inhaler pertaining to the present invention is preferably selected from a group comprising tiotropium, oxitropium, flutropium, ipratropium, glicopironium, flunisolid, beclomethasone, budesonide, fluticasone, mometasone, ciclesonide, rofleponide, dexamethasone, montelukast, methylcyclopropane acetic acid, sodium cromoglicat, nedocromil sodium, Npropylene, teophylline, roflumilast, ariflo (cilomilast), salmeterol, salbutamol, formoterol, terbutaline, carmoterol, indacaterol, cetirizine, levocetirizine, efletirizine, fexofenadine and their racemates, free base, enantiomers or diastereomers and
• the device pertaining to the present invention is used in the administration of the medicament in dry powder form which is utilized in the treatment of many respiratory diseases, particularly in asthma, chronic obstructive pulmonary disorder (COPD) and allergic rhinitis.
• the respiratory diseases include, but not restricted to, allergic or non-allergic asthma at any phases, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), exacerbation of airways hyperactivity, bronchiectasis, chronic obstructive pulmonary including emphysema and chronic bronchitis, airways or lung diseases (COPD, COAD or COLD), pneumoconiosis, aluminosis, anthracosis, asbestosis, chalicosis, ptilosis, siderosis, silicosis, tabacosis and byssinosis.
• ALI acute lung injury
• ARDS acute respiratory distress syndrome
• COAD chronic obstructive pulmonary including emphysema and chronic
• the device pertaining to the invention can be used in prophylactic or symptomatic treatment.
• the medicament in dry powder form which is preferably used in the symptomatic treatment of allergic asthma and COPD is adniinistered to the patient via the device pertaining to the present invention.
• the inhaler pertaining to the present invention is compared with the inhaler existing in the prior art and marketed under Diskus trade mark which does not have apertures to create turbulence. This comparison is based on DUSA analyses defined in American pharmacopeia which was conducted for these two inhalers comprising the same dry powder medicament in the same amount. 10 DUSA (Dose Uniformity Sampling Apparatus) analyses were conducted for each inhaler and the average values are taken into consideration. DUSA analyses of both inhalers are given in the tables below: Table 1 : Comparative DUSA analysis results of device 1 and device 2
• the amount of dry powder medicament contained in each blister is 13 mg in table 1 and 2; however, similar results were obtained in the conditions that the dry powder medicament in the blister is different than 13 mg.
• the inhaler pertaining to the invention makes a significant difference compared with the inhaler in the prior art which do not hold the specifications defined in the invention.

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• 2011
  • 2011-04-13 JP JP2013504864A patent/JP2013523378A/ja active Pending
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• 2012
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