Dry powder inhalers

The present invention relates to dry powder inhalers and cassettes such as removable and / or refillable feed cassettes for use in dry powder inhalers.

Asthma and other respiratory illnesses have long been treated by inhalation of appropriate medications. Over the years, the two most widely used and convenient treatment options are inhaling the drug from a drug solution or suspension in a pressurized metered dose nebulizer (pMDI), or A dry powder inhaler (DPI) was generally used to inhale a powder mixed with an excipient. Due to strong concerns about the link between the destruction of the Earth's ozone layer and chlorofluorocarbon (CFC) emissions, the use of such materials in pressurized inhalers has been phased out and interest in DPI systems has increased. ..

For example, UK Pat. No. 2242134 (Davies et al.), US Pat. No. 5,192,548 (Velasquez et al.), No. 5,619,984 (Hodson et al.), No. 5,657,748 (Braithwaite), WO 98/41255 (Jennings et al.), WO A large number of DPI systems or components for DPI systems have been shown, including those described in 01/21238 (Seppala) and US Pat. No. 2006/0081246 (Goede et al.).

In practice, most DPIs use either capsules such as blister packs or blister strips or bulk powder reservoirs sealed in individual containers in the form of blister or individual pre-measured doses. To do.

However, there are problems associated with accurately weighing small amounts (eg, 500 micrograms or less) of powder weighed from the raw material reservoir in the inhaler. For this reason, for many drugs (eg, highly effective drugs), it is necessary to add an excipient such as lactose powder in order to significantly increase the amount of powder to be weighed. However, such excipients are generally undesirable as they can later cause powder deaglomeration problems and can also cause dryness in the patient's mouth and other annoying effects.

In addition, the ingress of moisture (environmental humidity and / or moisture from the patient's breath, for example inadvertently exhaled into the inhaler), for example into the bulk powder reservoir, can cause serious problems. Many bioactive substances, such as pharmaceuticals delivered by inhalation, undergo physical or chemical changes and / or deterioration in the presence of water vapor. For example, powdered particles may recrystallize in the presence of adsorbed water vapor, which can actually increase the median particle size of the powdered material, thereby providing a suitable delivery site in the lungs. Penetration of particles into (eg, lower airways in the lungs) may be reduced.

DPIs in which the powder feed material (eg, powdered drug) is provided in the form of capsules or blisters are generally sealed in individual doses, typically the dose on the carrier component is the lid component. Since it is covered with and sealed, it has some good moisture resistance. The production of such capsules, blister packs or blister strips containing a small amount of powder accurately weighed into each capsule / blister used in DPI can be difficult and / or quite expensive. In addition, DPIs using such powder feeds typically require complex mechanisms (eg, lid peeling mechanisms, capsule / blister piercing mechanisms, etc.) to open individually sealed capsules or blister. ..

<p num="0008"> According to one aspect of the invention, a compartment comprising a chamber, a patient port communicating with said chamber, and an elongated carrier preloaded with multiple doses of a fine powder containing a bioactive substance. The powder is releasably retained on the surface of the carrier, the preloaded dose is sealed in the compartment, and the carrier is separated through an outlet provided in a moisture-proof sealing system. A compartment configured to be advanced from the chamber into the chamber and a portion of the carrier advanced from the compartment into the chamber, whereby the powder associated with the advance region of the carrier is passed through the patient port. The moisture-proof sealing system can be loosened during the advance of the carrier, and the moisture-proof sealing system is configured to be sealed prior to the advance of the carrier, with an advance mechanism for allowing release from the carrier for inhalation by the patient. Provided is a dry powder inhaler, configured and arranged to be loosened as the carrier advances and to be returned to a sealed configuration after release of the powder associated with said region of the carrier at the latest.</p><p num="0009"> Such a dry powder inhaler provides effective protection against moisture and moisture ingress, while at the same time providing individual doses and taking multiple doses without the need to seal each of those individual doses tightly. It is advantageous in that it allows the delivery of carriers preloaded with fine powder to provide the amount. In other words, the moisture-proof sealing system advantageously returns to the sealed configuration after the release of the powder associated with the advancing region of the carrier at the latest, before the next portion of the carrier advances, so that the fine powder is pre-dose. It is not necessary to weigh the carrier, and it is not necessary to cover and seal the carrier with a lid component such as a foil lid layer component.</p><p num="0010"> Further, in certain preferred embodiments, the moisture-proof sealing system is configured and arranged so that the moisture-proof sealing system is returned to its sealing configuration, at least prior to the release of the powder associated with said region of the carrier, with moisture. Protection against moisture ingress can be further promoted. The moisture-proof sealing system may be configured to return the moisture-proof sealing system to its sealing configuration when the carrier stops advancing, and may further enhance protection against moisture and moisture ingress in certain particularly preferred embodiments in place. it can. In embodiments described below, the moisture-proof sealing system can generally and advantageously operate in a "deadman's handle" fashion, with a seal applied to the supply compartment outlet when the carrier is not advanced, i.e., moisture-proof. It is particularly advantageous because the sealing system generally operates to automatically return to its sealing configuration as soon as the advance of the carrier is stopped. ("Returning the sealing system" or "returning the sealing system" as used herein means that the moisture-proof sealing system may be returned by itself or by the operation of individual mechanisms / elements. Will be understood.) The compartment can preferably be provided in a cassette that can be reversibly removed from the dry powder inhaler. Such cassettes themselves can be advantageous in that they can be used as powder reservoirs and / or supply units for dry powder inhalers, such as the original supply unit and / or refill supply unit.</p><p num="0011"> According to a second aspect of the invention, a device for storing the dry powder used in the dry powder inhaler is provided, the device being preloaded with multiple doses of fine powder containing a bioactive substance. A compartment containing the elongated carrier, the powder being provided in the form of a cassette containing a compartment that is releasably held on the surface of the carrier, the compartment being preloaded. The dosage is sealed in the compartment and the carrier is configured and arranged to allow the carrier to advance from the compartment to the outside of the compartment through an outlet provided in the moisture-proof sealing system, the device being dry powder. During use in the inhaler, a portion of the carrier is advanced so that the powder associated with the advancing area can be released from the carrier for inhalation by the patient through the patient port of the inhaler, and the moisture-proof sealing system provides the carrier. The moisture-proof sealing system is a hermetically sealed configuration prior to advancing the carrier, loosening during advancing the carrier and at the latest after releasing the powder associated with said region of the carrier. Returned to.</p><p num="0012"> In certain preferred embodiments of the device according to the aforementioned embodiments, there is an area of the carrier advanced within the chamber, thereby tightening at its "end" during the release of the powder associated with said area of the carrier. It is particularly advantageous to allow the powder associated with said region of the carrier to be released from the carrier for the patient to inhale through the patient port (hereinafter simply referred to as the "dose release region"). I understood. This bilateral tightening also advantageously reduces powder from other regions of the carrier after or before the dose release region in the chamber from detaching from the carrier when the powder in the dose release region is released. It has been found that allowing and / or preventing, thereby minimizing and / or preventing the accumulation of drifting powder in the inhaler, thereby improving the reproducibility of the dose released accordingly. Therefore, in certain embodiments, the device may preferably further comprise a first tightening system and a second tightening system, which at least release the powder associated with the dose release area. The dose release area between the first tightening system and the second tightening system is configured to be tightened during the release of the powder associated with the dose release area previously moved to the tightening configuration. And are placed. In other words, the dose release area is positioned between the two tightening systems and is tightened by the two systems prior to powder release. In other embodiments, for example, the moisture-proof sealing system is arranged and configured to return to the sealing configuration at least prior to the release of the powder associated with the dose release area, and the moisture-proof sealing system is also configured as a tightening system. It is preferable to be able to operate. Therefore, such embodiments may preferably have a tightening system in addition to the moisture-proof sealing system, which is moved to a tightening configuration at least prior to the release of the powder associated with the dose release area. The tightening system and the moisture-proof sealing system are configured and arranged in such a manner that the tightening system and the moisture-proof sealing system are of the carrier relative to each other. The area is configured and arranged to be tightened between the tightening system and the moisture-proof sealing system during the release of the powder associated with the dose release area. In other words, the dose release area is positioned between the moisture-proof sealing system and the second tightening system and is tightened by the two systems prior to the release of the powder associated with the dose release area.</p><p num="0013"> In the dry powder inhaler, double-sided tightening without utilizing the moisture-proof sealing system according to the first and second aspects described above can also be advantageously used. Thus, in a third aspect of the invention, the dry powder inhaler is an elongated carrier preloaded with a chamber, a patient port communicating with said chamber, and multiple doses of fine powder containing a bioactive substance. The powder is releasably held on the surface of the carrier, and a portion of the carrier is advanced into the chamber to release the powder associated with the advancing region of the carrier from the carrier so that the patient passes through the patient port. It comprises a forward mechanism for inhalation, a first tightening system and a second tightening system, the first and second tightening systems at least prior to the release of the powder associated with said region of the carrier. Configured and arranged to be driven into a tightening configuration so that the region of the carrier is associated with the first tightening system and the second tightening system during the release of the powder associated with the region of the carrier. Tightened between.</p><p num="0014"> The device according to the second aspect described herein, eg, a cassette for storing powder used in a dry powder inhaler, may be equipped with a suitable tightening system or multiple tightening systems.</p><p num="0015"> The plurality of tightening systems may also be provided in a storage device that does not include the moisture-proof sealing system according to the first and second aspects described above. Therefore, in a fourth aspect of the present invention, an apparatus for storing the dry powder used in the dry powder inhaler is provided, the apparatus being preloaded with a plurality of doses of fine powder containing a bioactive substance. An elongated carrier, comprising a carrier in which the powder is releasably held on the surface of the carrier, a first tightening system and a second tightening system, wherein the device is in a dry powder inhaler. During use, a portion of the carrier is advanced so that the powder associated with the advancing area can be released from the carrier for the patient to inhale through the patient port of the inhaler, and the first and second tightening systems are at least The region of the carrier is transferred to a tightening configuration prior to the release of the powder associated with the region of the carrier so that the region of the carrier is combined with the first tightening system during the release of the powder associated with the region of the carrier. It is configured and arranged to be tightened to and from the tightening system.</p><p num="0016"> The scope of the dependent claims defines a further embodiment of the present invention.</p>

Here, the present invention will be described in accordance with the accompanying drawings.<figref num="1">Partial cross-sectional views of its closed, partially open and fully open positions of an exemplary dry powder inhaler, respectively.</figref><figref num="2">Partial cross-sectional views of its closed, partially open and fully open positions of an exemplary dry powder inhaler, respectively.</figref><figref num="3">Partial cross-sectional views of its closed, partially open and fully open positions of an exemplary dry powder inhaler, respectively.</figref><figref num="4">Sectional view of a particular area of an exemplary dry powder inhaler in its closed, partially and fully open positions and in operation, respectively.</figref><figref num="5">Sectional view of a particular area of an exemplary dry powder inhaler in its closed, partially and fully open positions and in operation, respectively.</figref><figref num="6">Sectional view of a particular area of an exemplary dry powder inhaler in its closed, partially and fully open positions and in operation, respectively.</figref><figref num="7">Sectional view of a particular area of an exemplary dry powder inhaler in its closed, partially and fully open positions and in operation, respectively.</figref><figref num="8">Partial cross-sectional views of an additional specific area of an exemplary dry powder inhaler in its closed, partially open, and more incompletely open, and fully open positions, respectively.</figref><figref num="9">Partial cross-sectional views of an additional specific area of an exemplary dry powder inhaler in its closed, partially open, and more incompletely open, and fully open positions, respectively.</figref><figref num="10">Partial cross-sectional views of an additional specific area of an exemplary dry powder inhaler in its closed, partially open, and more incompletely open, and fully open positions, respectively.</figref><figref num="11">Partial cross-sectional views of an additional specific area of an exemplary dry powder inhaler in its closed, partially open, and more incompletely open, and fully open positions, respectively.</figref><figref num="12">Partial cross-sectional view of its sealed position after opening halfway through an additional specific area of an exemplary dry powder inhaler.</figref><figref num="13">An isometric view of a portion of the compartment of an exemplary dry powder inhaler. Indicates the supply spool and friction brake.</figref><figref num="14">Partial cross-sectional view of the area of the feed spool around which the elongated carrier is wound and the outer components of the friction brake.</figref>

It should be understood that the present invention covers all combinations of unique, preferred, desirable, favorable, advantageous and preferred embodiments of the invention described herein.

1 to 3 show partial cross-sectional views showing an exemplary dry powder inhaler (10) in its closed, partially open and fully open positions, respectively. The inhaler (10) includes a chamber (200) and a patient port in the form of a mouthpiece (300) in detail communicating with the chamber. In FIG. 1, the patient port is not visible because the mouthpiece is covered by the cover (301) in the closed position of the illustrated inhaler. The patient port (300) is visible only when the user opens the inhaler for use, i.e., when the mouthpiece cover (301) is opened as shown in FIGS. 2 and 3. The inhaler (10) also includes an elongated carrier (100) preloaded with a fine powder containing a bioactive substance (not shown).

Elongated carriers can be provided in various forms such as tapes, webs, belts or cords. The carrier is preferably provided in the form of tape or web. The elongated carrier can have any ratio of length and width, but said ratio is generally greater than 5: 1, usually greater than 10: 1, and more specifically about 100: 1 to about 1000: 1. Is. The width of the elongated carrier can typically be from 5 mm to 20 mm, eg 10 mm. The thickness of the elongated carrier can typically range from 75 micrometers to 500 micrometers, more specifically from 100 micrometers to 250 micrometers, and more specifically from about 120 micrometers to 175 micrometers. If desired, the elongated carrier may include, for example, a lid component for coating and / or sealing individual doses. However, such coating and sealing is generally not required in certain embodiments of the invention described herein, so the carrier provides a lid component that coats and seals individual doses. It is preferable not to include it.

Powders containing bioactive substances, typically pharmaceuticals, are releasably retained on the surface of the carrier. The powder may be retained on the carrier by attractive forces such as electrostatic attraction, van der Waals forces, physical attraction, mechanical restraints, and / or wedge cracking. Alternatively, the powder may be retained on the carrier by covering the powder with a lid component, but as previously indicated, it is not desirable to use a lid component (also herein). It is also unnecessary according to the specific aspect of the present invention described in (1). It is desirable not to hold the powder on the carrier with an adhesive or glue to promote favorable release properties. The aforementioned expression "mechanical restraint" generally refers to the powder particles being held onto the carrier by the inherent mechanical means of the carrier material (eg, in the interlaced fibers of the non-woven web). .. The expression "wedge split" generally refers to loading powder particles into a particular structure of an elongated carrier (eg, a microdent in a plastic elongated carrier, or a porous space of a non-woven elongated carrier). One or more surfaces of the carrier and, optionally, the interior of the carrier may be configured to assist in the retention of powder particles.

The carrier is composed of a wide range of natural and synthetic materials such as polyethylene, polypropylene, polyester (eg polyethylene terephthalate), polytetrafluoroethylene or copolymers thereof, ethylene vinyl alcohol, and one or more of cellulose. May be good. The material may be a non-woven fiber material, a coarse woven or fiber, a material with a surface pile, a film, a microporous material, a fine groove material, a twisted string of fibers, or any other suitable material or a plurality. It may be in the form of a composite of materials. Desirably, the carrier is a small surface with a depth or height of 500 micrometers or less and at least one other dimension typically having a size greater than 0.1 micrometers to facilitate the retention of powder particles. Consists of a material or material composite provided with a dent, depression, groove, recess, gap, opening or embossed surface structure. Various materials and specific forms of carriers suitable for use herein are disclosed in US Pat. No. 5,619,984 (Hodson et al.), The entire contents of said patent being incorporated herein by reference. Is done.

The elongated carrier morphology helps to some extent in the storage mode. For example, the string may conveniently be stored as a coil or wound around a spool, and the tape or web may be conveniently folded or wound around a spool, for example. In general, the elongated carrier is preferably wound around a spool.

As shown in the exemplary embodiments shown in FIGS. 1-3, the carrier (100) is first housed on the feed spool (102) and onto the intake spool (104) during use of the inhaler. You may move forward. Generally, during the use of the inhaler, a portion of the carrier is delivered into the chamber, whereby the powder associated with the forward region of the carrier is removed from the carrier for inhalation by the patient through the patient port during operation. To be released.

For ease of illustration and observation, FIGS. 1-3 show carriers with a shorter overall length than usual. The carrier (100) is housed in a compartment (105) preloaded with fine powders that provide multiple doses, which seals the preloaded dose in the compartment. As a result, the carrier can advance from the compartment through the outlet (completely invisible in FIGS. 1-3) provided in the moisture barrier sealing system (110) into the chamber (200). it can.

This is better seen in Figures 4-6, respectively, in the area around the compartment outlet of the exemplary inhaler and in the lower part of the chamber, where the mouthpiece cover is closed (before progress). ), Partially open position (in progress), fully open position (before powder release). In the figure, the compartment (105) is on the left side and the compartment wall (106) is provided with an exit (107) (best visible in FIG. 5) through which the carrier (100) advances. In the closed position shown in FIG. 4, a moisture-proof sealing system (110) is in a sealing configuration, in particular the seal (111) pushes the carrier and the outer surface (106a) of the compartment wall (106), which It can be seen that the outlet (107) of the compartment is sealed. As shown in FIG. 5, which shows the partially open position, when the user opens the mouthpiece cover, the moisture-proof sealing system loosens and the seal (111) disengages from the compartment outer wall surface (106a) and the carrier (100). ) Can move forward (more on this later). When the user fully opens the cover, or more simply, when the user completes the advance of the carrier, and before the powder associated with said advance area of the carrier is released, the moisture-proof sealing system Returning to the sealed configuration, as can be seen in FIG. 6, the seal (111) is again tightened to the outer surface (106a) of the carrier (100) and the wall (106) of the compartment (105), thereby the compartment. The outlet (107) is sealed.

In a preferred embodiment, the moisture-proof sealing system is configured and arranged such that the moisture-proof sealing system returns to its sealing configuration at least prior to the release of the powder associated with the dose release region of the carrier.

The moisture-proof sealing system preferably comprises a seal. The seal (s) is typically a component of the system that seals the outlet of the compartment when the system is in its sealed configuration. Suitable materials for moisture-proof seals may have a Shore A hardness value of 75 or less, specifically 65 or less (as determined by ASTM Test Number D2249). Suitable materials for moisture-proof seals may have a Shore A hardness value of 35 or higher, more particularly 45 or higher (as determined by ASTM Test Number D2249). Such seals are preferably elastic and therefore most preferably contain an elastomeric material such as silicone rubber. For example, EPDM and polypropylene blends such as those available under the trade name SANTOPRENE, or thermoplastic elastomers of styrene isoprene copolymers such as those available under the trade name KRATON are preferably used. Such elastomers may be co-molded with other components of the device (such as swivel components described below) and also provide hardness and compliance that provides optimal sealing when the moisture-proof sealing system is in its sealing configuration. May be selected to have. Elastomer material or simultaneous molding surface components may be provided on any or all of the associated sealing surfaces of the device (eg, all surfaces in contact with the carrier and forming part of the moisture barrier sealing system). Good. Any or all of the seals may have a molding profile that allows the thickness of the carrier, for example, the seal may have a slight recess into which the thickness of the carrier fits. Such recesses are preferably slightly shallower than the thickness of the carrier.

The compliance required for sealing materials is relative and depends on several factors. Specifically, the accuracy of the parts (manufactured) that determine the accuracy with which the seal and the compartment outlet fit together, the thickness of the seal, the area of the seal in contact with the compartment outlet, the elasticity of the carrier, the spring The use and its strength, as well as the degree of moisture required, all influence the selection of the optimum sealing material. In certain examples, the seal and compartment may be adequately fitted so that the inelastic seal material can provide adequate sealing and prevention of moisture ingress. Suitable inelastic sealing materials include plastics such as polyethylene, polypropylene, and acrylonitrile butadiene styrene (ABS). In one embodiment, the seal and other components of the device (such as swivel components) may be entirely composed of a single plastic material. In another embodiment, the device component (eg, swivel component) may be made of any elastic thermoplastic material such as ABS, or may be molded with an elastomer seal placed on the component. Good.

The compartment may advantageously accommodate the desiccator. The desiccator may preferably be provided in the form of a cartridge containing water and / or a moisture absorbing material. Such water and / or moisture absorbing materials are well known and are known as active alumina, aerogel, benzophenone, bentonite viscosity, calcium chloride, calcium hydride, calcium sulfate, copper (II) sulfate, lithium chloride, lithium bromide, magnesium sulfate. Examples thereof include magnesium, magnesium sulfate, magnesium perchlorate, molecular sieve, potassium carbonate, silica gel, sodium chlorate, sodium sulfate, and sodium benzophenone. The use of such a desiccator can be easily seen as component 108 in the diagrams of the exemplary embodiments of FIGS. 1-3.

Preferably, the compartment is configured such that the relative humidity in the compartment is maintained at a level of about 75% or less, more preferably 65% or less, most preferably 60% or less over a 30-day period. 30 days is a typical duration of intended patient use of the device described herein (ie, the last dose after the patient has removed the device from any secondary packaging such as a sealed pouch. Until you take the amount). For example, for a device containing 120 doses of 2 doses twice daily, the intended duration of use would be 30 days. In certain cases, it has been found that it is desirable to keep the relative humidity in the compartment above the minimum level in order to minimize and / or prevent unwanted electrostatic effects. Considering the aforementioned ranges, it is preferable to maintain the relative humidity (within the aforementioned ranges) at a level of about 20% or higher, more preferably 25% and most preferably 30% or higher in such examples. For certain embodiments in which the desiccator can accommodate the desiccator, in some cases it is desirable to pre-adjust the desiccator so that the initial relative humidity in the compartment is set to a particular target value. I found out. For example, the default relative humidity is in the target and / or required relative humidity range, eg, about 20% to about 30%, more preferably about 25% to about 35%, even more preferably about 30% to about 40%. It may be desirable to be close to the bottom edge.

It is preferred that the compartment comprises a single outlet, i.e., the outlet through which the elongated carrier passes is the only opening of the compartment.

The compartment may be made by injection molding a thermoplastic material such as high density polyethylene or a cyclic olefin copolymer. In one embodiment, the feed spool (102), along with an elongated tape (100) and desiccator (108), may be loaded onto the bottom of the compartment (105) so that the tape is attached to the capture spool (104). Passed through. The compartment is then closed by heat-sealing a foil laminated lid (not shown) on top of the compartment wall (106), whereby the compartment is completely closed from its outlet (107). In an alternative configuration, the lid may be a molded plastic component sealed on top of the compartment wall, for example by ultrasonic welding, thermal welding or adhesive bonding.

It is desirable that at least a portion, or most preferably all, of the walls of the compartment be made of and / or constructed of a material such that the walls (s) provide a moisture barrier. Specifically, the wall (s) is 12 g / (m).²Sun) (38 ° C, 90% RH) less than moisture permeability (WVTR), more preferably 6 g / (m)²WVTR below (38 ° C, 90% RH), and even more preferably 3 g / (m)²Sun) (38 ° C, 90% RH) WVTR, and most preferably 1 g / (m)²It is desirable to have a WVTR of (38 ° C, 90% Rh).

WVTR may be measured at a relative humidity of 38 ° C / 90% by gravimetric methods such as ASTM E96 / E96M-05, Procedure E, desiccator method.

Preferably, at least a portion, or more preferably all, of the walls of the compartment is made of a material that contains a low water vapor (moisture) permeable material, i.e. a moisture barrier material. Moisture-proof layer material is 12 g / (m) when such material has a thickness of 100 micrometers.²Sun) (38 ° C, 90% RH) less than moisture permeability (WVTR), specifically 6g / (m)²Sun) (38 ° C, 90% RH) or less WVTR, more specifically 3g / (m)²WVTR below (38 ° C, 90% RH), most preferably 1 g / (m)²Can be described as a material with a WVTR of (38 ° C, 90% RH) or less.

The compartment wall (s) may be a single material (eg, a moisture barrier material) or a combination of materials (eg, a variety of moisture barrier materials provided per region or as a combination of layers within the wall. , Or may be made of a moisture-proof layer material (s) in combination with other materials. As a second alternative example, the rear wall and side walls may be made of a polymeric moisture barrier material (such as high density polyethylene (HDPE)) and the front wall (lid) may be a metal foil (aluminum foil or It may be made of a laminated foil consisting of one or more metal layers). In another example, the walls of the compartment (s) may be made up of two or more layers, each layer providing different impervious properties. For example, for pharmaceuticals that are susceptible to long-term exposure to oxygen, it is desirable with materials that provide desirable moisture barrier properties, but typically do not provide favorable oxygen barrier properties (such as high density polyethylene (HDPE)). It may be preferable to use a material that provides oxygen blocking properties (ethylene vinyl alcohol, nylon 6, nylon 66, polyvinylidene chloride, polyvinyl acetate, etc.). Alternatively, the walls of the compartment (s) may include two or more layers, for example for ease of manufacture and / or stability. For example, the walls of the compartment (s) may be laminated to a suitable polymer layer or made of aluminum foil sandwiched between two suitable polymer layers, or aluminum may be made of aluminum. It may be adhered on a suitable polymer layer (eg, creating a metallized polyethylene terephthalate layer or a metallized nylon layer), or two metallized plastic layers (eg, aluminum adhered on polyethylene or polypropylene). However, they may be laminated with the metallized surfaces facing each other. Another alternative is to stack a polymeric moisture barrier layer on another polymeric layer, especially for strength. Further, the walls of the compartment (s) may include an outer layer made of a moisture barrier material and an inner layer containing a desiccator material. This may be done, for example, using a two-shot molding process, in which case the outer layer. Is a polymer with low moisture permeability (eg HDPE, polypropylene (PP), or cyclic olefin copolymer), the inner layer is a dry polymer (eg nylon), or the outer layer is a polymer. It may be made of a moisture-proof layer material, the inner surface of which is lined with a non-polymer in which desiccator particles are embedded. With respect to the latter, the material for the desiccator particles can be selected from the material list described above. Additional examples of combinations include blending a moisture barrier material (eg PE) with another material (eg ethylene vinyl acetate (EVA)).

Suitable moisture barrier materials include metal foils, in particular aluminum foils at least 8 micrometers, more specifically at least 10 micrometers, even more specifically at least 15 micrometers, most specifically at least. It has a thickness of 25 micrometers. The desired and / or required thickness depends on how the foil is used. For example, the aluminum foil laminated between the polymeric moisture barriers may be only 8 micrometers thick, but for simple aluminum foils it is desirable to use foils with a thickness of 25 micrometers or more. And / or may be necessary. The lid is preferably 80 micrometers thick, includes an 8 micrometer aluminum foil layer sandwiched between layers of low density polyethylene, and has an outer coating of polyethylene terephthalate. Other suitable moisture-proof layer materials include thin-film aluminum coatings (specifically having a thickness of at least 0.1 micrometer), vapor-deposited silicon oxide coatings (specifically having a thickness of at least 0.04 micrometers), and thin-film deposition diamonds. Coatings such as glass coatings can be mentioned (these coatings and methods of forming these coatings are described in US Pat. No. 6,696,157 (David et al.), The entire contents of which are described herein. Incorporated into the book). More suitable moisture barrier materials include polyvinyl chloride (hard or plasticized; specifically hard PVC), ethylene vinyl alcohol (specifically high ethylene content, more specifically at least 30% polyethylene content). Has ethylene vinyl alcohol), polychlorinated nitrile, polyethylene terephthalate, polyethylene naphthalate, polyolefin (specifically, polypropylene, a copolymer of polyethylene and polypropylene, biaxially stretched polypropylene), polyethylene (low density polyethylene (density 0.925 g / cm)³Including), linear low density polyethylene, medium density polyethylene (density 0.925 g / cm)³Super and 0.94g / cm³Below), high density polyethylene (density 0.94 g / cm)³Polymer materials such as super), cyclic olefin copolymers (eg, those available under the trade name TOPAS), polyvinylidene chloride, polychlorotrifluoroethylene, and liquid crystal polymers. Among polyethylenes, high-density polyethylene is particularly advantageous as a moisture-proof layer material. Polymers produced using metallocene catalysts, specifically polyolefins (including low density polyethylene, linear low density polyethylene, medium density polyethylene, high density polyethylene, polypropylene, biaxially stretched polypropylene) are such. The use of catalysts generally allows the production of polymers with a narrower molecular weight distribution than polymers using the more traditional Ziegler-Natta catalysts, thus allowing tighter control of the composition and moisture barrier properties. It is preferable in that.

If necessary, the wall or part of the wall of the compartment can be injection molded (eg, single-shot or multi-shot molded), as well as simultaneous extrusion, extrusion bonding, vacuum metallization, or as desired and / or as needed. It may be generated by a combination of these methods.

Depending on the choice of wall material (s) and certain agents, at least part or more preferably all of the walls of the compartment, usually to such a device, without adding too much material to make the device unwieldy. It may be desirable to make it thicker than the thickness used. Specifically, for non-foil-based wall materials (eg, neither metal-leaf-based nor polymer and metal-leaf laminate-based), at least a portion, or preferably all, of the walls of the compartment, preferably about. It may be at least 500 micrometers, more preferably at least about 1000 micrometers, and most preferably at least about 1250 micrometers. Also, it is desirable that at least part or more preferably all of the walls of the compartment be 4 mm or less, more preferably 3 mm or less, and most preferably 2 mm or less.

As mentioned above, the compartment may preferably be provided in a cassette that can be reversibly removed from the dry powder inhaler. Such cassettes also preferably include an uptake spool so that the user can easily insert the cassette into the dry powder inhaler and / or easily remove the cassette. For long-term storage as the original supply unit and / or refill supply unit, the cassette may be sealed in a container such as a pouch.

Figure 7 shows the portion around the compartment outlet and inferior portion of an exemplary inhaler chamber at the time of operation, that is, the powder associated with the dose release area is inhaled by the patient through the patient port. It is a figure of the part released from the carrier.

Various means are known to release the powder from one region of the carrier, regardless of the patient's inspiratory effort. Many such means are disclosed in US Pat. No. 5,619,984 (Hodson et al.), Included systems that provide mechanical effort (eg, shock, vibration, gas flow, etc.) or electrostatic effort. The means for releasing the powder from the carrier during inhalation is preferably actuated in response to the patient's inhalation so that the operation of the release mechanism does not have to be synchronized with the inhalation. Airflow detection is conveniently performed by movable blades located in the chamber or patient port, and the movement of the blades activates the release mechanism.

In an exemplary embodiment, the release of the powder is initiated in response to the patient's inhalation. Specifically, when the user inhales, the movable blades in the chamber (not shown; the outer part of the blade positioning pin (201) in FIGS. 1-3) release the trigger mechanism (not shown) and then: The trigger mechanism releases the hammer (205, shown in FIGS. 4-7). The hammer then hits the carrier (100), so that the powder (90) associated with the dose release area is released into the chamber (200) (as shown in FIG. 7).

It is particularly advantageous that the dose release area of the carrier (ie, the area of the portion advanced into the chamber for powder release of the carrier) is tightened between the first tightening system and the second tightening system. It turned out that there was. As mentioned above, during operation, by tightening the area of the carrier to be struck between the two tightening systems, when the powder associated with the dose release area is released, the other area of the carrier (ie, intended). It is possible to reduce and / or prevent the removal of powder from (the area after or before the dose release area) that has been applied. This can advantageously improve the reproducibility of the dose released.

Bilateral tightening can be achieved by providing a first tightening system and a second tightening system, the first and second tightening systems at least before the release of the powder associated with the dose release area. The region of the carrier is configured to be clamped between the first tightening system and the second tightening system during the release of the powder associated with the region of the carrier. And are placed. As mentioned earlier, one aspect of the invention includes a dry powder inhaler that comprises such a bilateral tightening system but does not utilize a moisture barrier sealing system. Also, as mentioned earlier, specific embodiments according to certain other aspects of the invention include inhalers and / or cassettes that include such bilateral tightening systems, in addition to moisture-proof sealing systems.

According to the present invention, an inhaler and / or cassette comprising a moisture-proof sealing system configured and arranged such that the moisture-proof sealing system is returned to its sealing configuration at least prior to the release of the powder associated with the dose release region. In certain embodiments, bilateral tightening can be achieved in an alternative way, i.e., in which the moisture-proof sealing system acts as a tightening system. Such embodiments include a tightening system in addition to a moisture-proof sealing system, the tightening system being configured and arranged to be transferred to a tightening configuration at least prior to the release of the powder associated with the dose release area. The tightening system and the moisture-proof sealing system are configured such that the dose-releasing area is clamped between the tightening system and the moisture-proof sealing system during the release of the powder associated with the dose-releasing area to each other. To. In other words, the dose release area is positioned between the moisture-proof sealing system and the second tightening system and is tightened by the two systems prior to dose release.

This latter option can be better understood by examining exemplary embodiments. As described in connection with FIGS. 4-6, the moisture-proof sealing system (110), specifically its seal (111), seals the outlet (107) of the compartment (105) with its sealing configuration. At the same time, the carrier (100) is tightened against the wall (106) of the compartment (105) between the seal (111) and the outer surface (106a) of the compartment wall (106). See, for example, FIGS. 6 and 7 in comparison with FIG. Thus, in an exemplary embodiment, the moisture-proof sealing system also serves as a tightening system. With reference to FIG. 7, it will be understood that the region of the carrier (100) advanced within the chamber (200) is tightened between the two systems. In this embodiment, the tip of the region is tightened to the grip (126) of the tightening system and the rear end is tightened by the seal (111) of the moisture-proof sealing system. When the hammer (205) hits the carrier (100) and releases the powder (90) associated with the area of the carrier placed between the tightenings, when the other area of the carrier (when the hammer hits) from that area of the carrier. The transfer of energy to the area before and after the area intended for dose release of the carrier in the chamber) is minimized and / or prevented. In this way, the unwanted release of powder from the region still within the carrier feeding compartment (105) is the undesired release of residual and / or residual powder from the already used region of the carrier within the uptake region. As with, it may be minimized and / or prevented.

In an exemplary embodiment, the second tightening system (125) is formed as an extension (118) of the swivel component (112) used in the moisture-proof sealing system (110).

Here, with reference to FIGS. 8-11, the closed position (FIG. 8) and the partially open position (FIG. 9) of the region including the exemplary inhaler supply and intake spool, compartment outlet and flow chamber, respectively. ), The position between the partially opened position and the fully opened position (FIG. 10), and the detailed partial cross-sectional view of the fully opened position (11) (here, without a cover). (Fig. 8, Fig. 9 and Fig. 11 correspond to Fig. 1, Fig. 2 and Fig. 3, and Fig. 4, Fig. 5 and Fig. 6, respectively.) The swivel component (112) is a pin with a front plate (113) having a quasi-triangular structure (see, eg, FIGS. 8-11) and a quasi-V-shaped rib rear structure (114) and a seal (111). It has a structure (see FIGS. 4 to 7) in which the shape structure (115) is combined. One end of the aforementioned quasi-V-shaped rib rear structure (the end distal to the seal (111)) provides a grip (126) for the tightening system. The other end is provided in the form of a partial cylinder (116). The swivel component (112) is held in place by a pin (not shown) protruding from the rear of the partial cylinder (116), which pin is held in a suitable cylindrical hole in the main frame or chassis of the suction device. To. The partial cylinder (116) is positioned within the "socket" of the curved portion of the compartment wall (106). There is a gap between the partial cylinder (116) and the "socket", and as you can see, the partial cylinder "rotates / turns" within the "socket". Furthermore, comparing FIGS. 8-11, the swivel component (112) swivels around an axis (P) approximately perpendicular to the front plate (113), with the axis (P) within the partial cylinder (116). It is located near the seal (111). (For the printed figure, the axis (P) is perpendicular to the page of the figure, to the left, and below the sticker.) As best seen in FIGS. 4-7, an exemplary embodiment has a post (120) and a torsion spring (121). The post (120) is located near the quasi-V-shaped rib rear structure but opposite to the seal (111). The torsion spring (121) engages a portion of the rear structure (114) of the swivel component (112) and exerts a force on the swivel component so that the seal (111) is urged in the direction of the sealing configuration. The outlet (107) of the compartment (105) is sealed. For example, comparing FIGS. 4 and 5 shows that the torsion spring (121) exerts a substantially counterclockwise force on the swivel component. The swivel movement of the swivel component is restricted by providing a slot (117) in the front plate structure and passing one end of a post (120) through the slot. With reference to FIG. 8 where the exemplary inhaler is in the closed position, the post (120) is next to the bottom of the slot (117) and the seal (111) seals the outlet (107) and at the same time the carrier ( Tighten 100) to the outer surface of the compartment and allow the peripheral portion (100a) near the carrier intake spool (104) to sag.

As can be seen in Figure 9 where the mouthpiece cover is in the partially open position, when the user opens the mouthpiece cover of the exemplary inhaler (301 in Figures 1-3), the intake spool is rotated clockwise. It rotates and the outer bend of the carrier around the intake spool is pulled tight. With respect to the end of the upper extension / grip of the swivel component (112) (118 is shown in FIG. 9 and 126 is not shown in FIG. 9) (more specifically, the grip (126) above. The newly generated tension of the carrier (100) and the resulting force (against the end of the upper portion of the so-called rear structure) overcomes the force of the torsion spring (121) and thus substantially the swivel component (112). Rotate clockwise and at the same time loosen (remove) the moisture-proof sealing system, thereby opening the outlet (107) of the compartment (105). Referring to FIG. 9, the post (120) is adjacent to the top of the slot (117), the seal (111) is moved slightly clockwise downward, and the carrier grips above the seal (111). Moving forward on (126, not shown), the intake spool is rotated clockwise by about 90-100 degrees from the position shown in FIG. 8 to the position shown in FIG. The latter is best understood by referring to the movement of the quasi-semicircular cam feature shape (145) on the anterior ratchet (144) on the capture spool (104), which the capture spool is about 90. Indicates that it has been rotated ~ 100 degrees clockwise.

As can be seen in FIG. 10, the intake spool rotates clockwise as the user continues to open the example inhaler mouthpiece cover (301) between the partially open and fully open positions. Continuing, the aforementioned cam (145) on the forward ratchet (144) begins to engage the heel (119) of the swivel component (112), which causes the swivel component to rotate / turn counterclockwise. The grip (126) of the tightening system (125) moves towards the chamber wall (202). Finally, when the user fully opens the mouthpiece cover (301) (fully open position as shown in FIG. 11), the grip (126) of the tightening system (125) is replaced by the carrier (100) / chamber wall (100). Finally fully engaged with 202) (ie, tightening the carrier (100) against the outer surface (202a) of the chamber wall (202)), the moisture-proof system seal (111) is attached to the carrier (100) / compartment. Engage with the wall (106) (ie, tighten the carrier (100) against the outer surface (106a) of the compartment wall (106)), resulting in a gap between the seal (111) and the grip (126). The dose release area is tightened. Due to the elastomer seal (111) within the moisture-proof sealing system (110), this seal (111) is such that the grip (126) of the tightening system (125) is perfect against the surface (202a) of the chamber wall (202). The surface (106a) of the compartment wall (106) can be completely sealed prior to sealing. The use of the cam (145) and its engagement of the swivel component (112) with the heel (119) facilitates the sealing of the grip (126) with respect to the chamber wall (202). At this time, the exemplary inhaler is ready for the release of the powder associated with the dose release area (the release has already been described in connection with FIG. 7).

In an alternative embodiment, the swivel component (112) may be substituted by a component that moves linearly to tighten and loosen the carrier, said component being apparent to those skilled in the art who have studied the present disclosure and exemplary embodiments. It is arranged and configured by any suitable method.

The tightening system may include a grip or a plurality of grips. Such grips (s) have the form of properly tightening the carrier and also include such suitable materials. Suitable materials for gripping tightening systems may have a Shore A hardness of 85 or less (as determined by ASTM Test Number D2249), and more specifically 75 or less. Suitable materials for tightening system grips may have a Shore A hardness of 35 or higher (as determined by ASTM Test Number D2249), and more specifically 45 or higher. The grip may be made of the same material as another (eg, swivel) component and is therefore adjacent to that component. Alternatively, the grip may include an elastomeric material, eg, an elastomer grip component that is attached to the swivel component in the same way that the moisture barrier seal is attached to the swivel component. Alternatively, the grip may be two-shot molded into the swivel component. One of the functions of bilateral tightening is the region outside the dose release region of the carrier by absorbing some or all of the carrier's vibrations that occur during the release of the powder from the dose release region. If necessary, this will provide an elastomeric material (specifically, for example, a low Shore A hardness value of 35-55) on both the moisture-proof grip (s) and the seal, as it will prevent or reduce the transmission to. May be facilitated by the use of (such as materials with). Increasing the distance that the fasteners act along the area of the carrier may enhance the braking effect. However, such parameters must be optimized by other performance considerations for the device, such as powder turbulence due to contact with fasteners and / or the need to advance the carrier longer than the length of the dose release region. Must be.

In a particularly preferred embodiment of the device according to the particular embodiment described herein, the moisture-proof sealing system is configured and arranged such that the moisture-proof sealing system returns to its sealing configuration when the carrier stops progressing. A common function of such a particularly preferred embodiment is that the patient substitutes by exerting a force on a user-operated forward element (eg, by pulling / holding the mouthpiece cover opening of an exemplary inhaler. When the user-operated progress element of the carrier is advanced (which may include a button or lever), the carrier is tensioned (part of the force exerted by the patient is via the applicable device component). The tension becomes the tension of the carrier), which removes the moisture barrier sealing system and opens the compartment outlet, which allows the carrier to easily pass through the outlet. As soon as the carrier stops advancing (in other words, as soon as the patient stops applying force to the user-operated advancing element), the tension of the carrier is relaxed or reduced and the carrier sags, thereby a moisture-proof sealing system. Returns to its sealed position (eg, spontaneously (eg, by elastic strain energy) or under the action of individual components (such as torsion springs (as in an exemplary inhaler)). In one embodiment, the drug supply compartment is opened only when the carrier needs to be advanced and is sealed when it does not need to be opened to advance the tape, with the sealing and opening being "automatic". It is particularly advantageous in that it is not compromised by forgetfulness or confusion on the part of the patient. An additional advantage of such a sealing mechanism is that exhaled breath was inadvertently inhaled into the inhaler when the tape was not advanced. In some cases, the drug supply compartment is protected from moisture ingress due to exhalation, and drug powder, which may come off the tape supply, cannot leak from the drug supply compartment.

In the exemplary inhalers described herein, it is preferred that the moisture-proof sealing system, in particular its seal, be coupled to a swivel member that is engaged with a spring, the spring being separated from the moisture-proof seal. When the swivel member is urged in a direction that seals the chamber outlet and the carrier is advanced under the tension associated with the advancement of the carrier, the swivel member rotates in the opposite direction, resulting in the moisture-proof seal being removed. The compartment outlet is opened, which allows the carrier to advance from the outlet, and when the carrier stops advancing, the swivel member rotates in its original direction under the tension of the spring, resulting in a moisture-proof seal in the compartment. Seal the outlet.

FIG. 12 is an exemplary inhaler achieved by the user partially advancing the carrier and then stopping the advance of the carrier (ie, stopping pulling / holding the mouthpiece cover (301) opening). Indicates the sealing position of. When the mouthpiece cover is advanced, the tension of the carrier (100) causes the mouthpiece cover (301), the front ratchet and the intake spool (104) to rotate counterclockwise by about 10 degrees. This backward rotation releases the tension on the carrier (100), at which the seal (111) of the moisture-proof sealing system reengages with the compartment wall (106), thereby the swivel component (100). 112) creates enough slack to rotate counterclockwise under the force of the torsion spring (121) until the outlet slot (107) of the compartment (105) is resealed.

As mentioned above, the elongated carrier may be wound around a spool in the supply compartment. The spool preferably includes an unspool prevention mechanism. Unspooling prevention mechanisms can utilize friction braking, ratchet systems, or some other mechanism to prevent carrier unspooling and reduce or prevent supply spool rotation unrelated to carrier advancement. desirable. Also, the unspooling prevention mechanism preferably provides resistance to the movement of the elongated carrier while the carrier is being advanced, especially immediately after the moisture barrier sealing system has loosened. This resistance to movement facilitates the generation / maintenance of tension in the carrier during carrier advancement.

Such a mechanism is best understood by reference to FIGS. 13 and 14, where FIG. 13 and FIG. 14 are exemplary dry powder inhalers showing feed spool and unspooling prevention mechanisms, specifically friction brakes, respectively. An isometric view of a portion of the compartment of the vessel and a partial cross-sectional view of the combined region of the feed spool around which the elongated carrier is wound and the outer components of the friction brake are shown. The feed spool (102) is wrapped with an elongated carrier (100) preloaded with fine powder. As can be seen from FIGS. 13 and 14, the lower portion of the feed spool has an annular flange (151) for holding the carrier and a cylindrical core (152) around which the elongated carrier is wound. The compartment (105) has a supply post (153) that provides a shaft on which the supply spool (102) rotates. The feed post is approximately cylindrical and has a smooth surface. Alternatively, the surface of the supply post may be splined and the splines are evenly distributed around the perimeter parallel to the axis. The inside (155) of the cylindrical core extends upward from about halfway up and is arranged upward and inward to contact the supply post and provide frictional interference in the contact area (157). Has a lip (156). The lip has two opposite wide slits (158a, b) extending from the contact area (157) to the middle of the cylindrical core (152). These slits move the lip slightly away from the feed post under the action of a tight fit, but can be retained by the elastic properties of the feed spool material. If the feed post is splined, the lip contact area may also have splines. The two sets of splines allow the feed spool to rotate around the feed post only when the post spline pushes the spool spline slightly backwards, so that the spool clicks in a defined small increment during use. Make a noise and go around. The friction brake is provided by interference within the contact area (157), allowing the elongated carrier to remain tightly wound around the feed spool during use.

The fine powders used in the devices described herein generally have a mass median particle size of typically 10 micrometers or less. More preferably, the median mass diameter is 7 microns or less, more preferably 5 microns or less, and most preferably the average mass diameter is in the range of 1 micron to 3 microns, at least 90% by mass of the particles. Has a diameter of less than 5 microns.

The powder is a fluid energy mill driven by compressed air, for example, as shown in "Drug Delivery to the Respiratory Tract", edited by D. Ganderton and T. Jones, publ. Ellis Horwood, Chichester (1987), pp. 89-90. May be pulverized by the use of, or by repeated step pulverization, or by the use of a closed loop pulverization system.

As previously indicated, the fine powder is preferably filled into a plurality of microrecesses on the surface of an elongated carrier, specifically a flexible, elongated carrier such as a web or tape. The recesses may preferably be separated at intervals of about 20-2000 micrometers, more preferably at intervals of about 300-2000 micrometers. The recess is preferably a carrier 1 cm²It may be about 25 to 1000 pieces per unit. The volume of each recess and the spacing or number of recesses determine the particular desired use of the resulting filled elongated carrier and, in the case of bioactive substances (eg, pharmaceuticals), the potency of the particular substance and of the substance. It depends on the area of the carrier material intended to provide a single dose. Typically, the carrier material should have a substantially uniform recess volume per unit area when considered for the size of the area of a single dose or other functional unit. For example, such dose regions may have 200-2000 discrete microrecesses, each with a depth of about 45 micrometers and a diameter of about 150 micrometers. Advantageously, in order to prevent the "quantization effect" caused by the lateral variation of the slit position, the rows of microrecesses along the longitudinal axis of the elongated carrier are not exactly parallel to the axis, but with respect to the axis. It is slanted at a slight angle (eg 0.5 ° to 2 °). The oblique angle can be selected to match the spacing of the microrecesses and the desired slit width, so that no matter where the slits are laterally, each dose (eg 20 mm x 10 mm) There will be an accurate total microrecess volume on the region). The microrecesses are preferably provided by cast embossing of a low density polyethylene (LDPE) layer by using a patterning roller that is photolithographically patterned, etched or diamond processed. Preferably, the LDPE layer described above is provided on a paper backing material or a backing material of a paper / LDPE laminate (having paper between two LDPE layers).

Such packed elongated carriers are particularly conveniently used for administration of bioactive substances by inhalation, in particular pharmaceuticals. In addition, elongated carriers with microrecesses are substantially subjected to such fine powders by the methods disclosed, for example in WO 2007/112267 (Hodson and Wilby), the content of which is incorporated by reference in its entirety. It can be filled accurately and evenly, which allows for accurate and uniform release of the dosage of the bioactive substance.

For delivery by inhalation, suitable pharmaceuticals include any drug or combination drug that can be administered by inhalation, i.e., solid or can be incorporated into a solid carrier. Suitable agents include agents for treating respiratory disorders, such as bronchodilators, anti-inflammatory agents (eg, corticosteroids), antiallergic agents, anti-asthma agents, antihistamines, anticholinergic agents. .. Inhalation delivery includes appetite suppressants, antidepressants, antihypertensive agents, antineoplastic agents, antitussives, anti-infective agents (eg, antibacterial agents, antibiotics, antiviral agents), migraine treatments, anti-pepsin. Agents, dopamine agonists, analgesics, sympathetic beta blockers, cardiovascular agents, hypoglycemic agents, immunomodulators, pulmonary surfactants, prostaglandins, sympathomimetics, tranquilizers, steroids, vitamins and sex Hormones, vaccines, and other therapeutic proteins and peptides can be used.

For delivery by inhalation, the drug used is about 25 cm on an elongated carrier.²Less than, preferably about 5 cm²It is preferred to have the ability to carry a single dose in less than an area. More preferably, the elongated carrier so containing the drug is 0.25 to 2.5 cm of the elongated carrier when used in a device as described in US Pat. No. 5,408,994 or 5,619,984.², Most preferably 1.5 ~ 2.25 cm²It is of the type that includes a single dose. In other words, the filled elongated carrier is 1 cm.²Conveniently containing about 25-500 μg of powder per unit, the potency of the agent is preferably the aforementioned 0.25-2.5 cm of elongated carrier²On top of which a single dose can be maintained.

Illustrative agents that can be used for delivery by inhalation include albuterol, revalterol, terbutalin, phenotelol, metaproterenol, isoproterenol, isoetarin, vitorterol, epinephrine, turobterol, vanbuterol, leproterol, adrenaline, ipratropium, oxytropium, Thiotropium, daratetropium, acridinium, glycopyrronium, bechrometasone, butyxocolt, betamethasone, fluticasone, budesonide, mometasone, cyclesonide, lofreponide, procaterol, indacatelol, TA2005 (carmoterol), omalismab, montelukas, sodium Dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate, prednison, methylprednisolone acetate, ogremirast, dileutone, insulin, atropin, prednisolone, benzphetamine, chlorfenthermin, amitryptrin, imiplamine, chronidin, actinomycin, bromocryptin, fentanyl , Leuprolide, alpha-1-antitrypsine, interferon, human growth hormone, propranolol, lasicolton, triamsinolone, dinoprost, xylometazoline, diazepam, lorazepam, folic acid, nicotinic acid amide, clembuterol, ethynyl estradiol, levonol gestrel, and their pharmaceuticals. Acceptable salts and esters (albuterol sulfate, formoterol fumarate, salbutamol xinafoate, acridinium bromide, glycopyrronium bromide, vechrometazone dipropionate, triamsinolone acetonide, fluticasone propionate, fluticasone flocate, odor (Thiotropium b., Leuprolide acetate and mometasone furoate)), but are not limited thereto.

Additional agents that can be delivered by inhalation include aspirin, acetaminophen, ibprofen, naproxene sodium, buprenorphine hydrochloride, propoxyphene hydrochloride, propoxyphenapsilate, meperidine hydrochloride, hydromorphone hydrochloride, morphine sulfate, fentanyl citrate, Oxycodone hydrochloride, codeine phosphate, dihydrocodein hydrogen tartrate, pentazosin hydrochloride, hydrocodone hydrogen tartrate, revorphanol tartrate, diflunisal, naltrexone, oxycodone, safentanyl, remifentanyl, heroine, trolamine salicylate, metadon hydrochloride, nalbufin hydrochloride, nalolfin, Tetrahydrocannabinol, mephenamic acid, butorphanol tartrate, choline salicylate, butalbital, phenyltroxamine citrate, diphenhydramine citrate, mettrimeprazine, cinnamedrine hydrochloride, meprobamate, ergotamine tartrate, propanolol hydrochloride, isometeptene mucate), dichlorophenazone, sumatriptan, lysatriptan, zormitriptan, naratriptan, eletriptan, barbiturate (eg pentobarbital, pentobarbital sodium, secobarbital sodium), benzodiazepine (eg furlazepam hydrochloride, triazolam, etc.) Temazeparm, midazolam hydrochloride, lorazepam, buspirone hydrochloride enanihate), methyltestosterone, fluorimesterone, testosterone cypionate), estrogen (eg estradiol, estropipate, conjugated follicular hormone) progestin (eg methoxyprogesterone acetate, noretindrone acetate), levothyroxine sodium, human insulin, purified Cow insulin, refined pig insulin, glipizide, chlorpropamide, glipizide, tolbutamide, trazamide, logiglitazone, pioglitazone, troglitazone, clofibrate, dextrotyrosin sodium, probucol, robastatin, rosbastatin, niacin, DNase, Arginase, superoxididismutase, lipase, calcitonion, alpha-1-antitrypsin, interferon, sense or antisense nucleic acids encoding proteins suitable for delivery by inhalation, erythropoietin, famotidine, cimetidine, hydrochloric acid Examples include lanitidine, omeprazole, esomeprazole, lanzoprazole, meclizine hydrochloride, navilon, prochlorperazine, dimenhydrinate, promethazine hydrochloride, thiethylperazine, scopolamine, sildenafil, baldenafil, siromirast, imikimod or resiquimod. Not limited to these. If desired, these agents may be delivered in the form of alternative salts. Examples include, but are not limited to, meclizine acid, nabilone, prochlorperazine, dimenhydrinate, promethazine hydrochloride, thiethylperazine, scopolamine, sildenafil, vardenafil, syromilast, imiquimod or resiquimod. If desired, these agents may be delivered in the form of alternative salts. Examples include, but are not limited to, meclizine acid, nabilone, prochlorperazine, dimenhydrinate, promethazine hydrochloride, thiethylperazine, scopolamine, sildenafil, vardenafil, syromilast, imiquimod or resiquimod. If desired, these agents may be delivered in the form of alternative salts.

The agent may comprise one or more agents having one or more particle morphologies and may include one or more physiologically acceptable or inert excipients.