Patent Document

RELATED APPLICATION  
       [0001]    This application is a continuation-in-part of U.S. patent application Ser. No. 09/567,352, filed May 9, 2000, the disclosure of which is hereby incorporated by reference. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    1. Field of the Invention  
           [0003]    The present invention is directed to an inhalation actuated pulmonary drug delivery device used in the delivery of fluid dispensations from a drug containing canister, the delivery device providing a metered dose of drug or other therapeutic agent when the patient inhales from the device or when the patient compresses a canister section of the device.  
           [0004]    2. Brief Description of Related Art  
           [0005]    There are a variety of inhalation devices which release aerosol medication, either in a continuous spray or in a predetermined amount of medication, commonly referred to as a metered dose. The spray is applied directly into the patient&#39;s mouth, nasal area or respiratory airways. Typically, these devices are actuated by the pressure applied by the user&#39;s fingers, button action, or other related manual techniques. While there are devices which are activated by the inhalation of the users, some of which are very satisfactory, as with all things, variations or improvements are desirable.  
           [0006]    Metered dose aerosol canisters of the medicine to be inhaled into the mouth, nasal areas or respiratory airways are manufactured by a variety of pharmaceutical companies. Therapeutic agents commonly delivered by the inhalation route include bronchodilators (B2 agonists and anticholinergics), corticosteroids, and anti-allergics. Inhalation may also be a viable route for anti-infective, vaccinating, systemically acting and diagnostic agents, as well as anti-leukotrienes, and-proteases and the like. Metered dose aerosols are much the same as non-metered aerosol except that when the valve is depressed, a continuous spray is not discharged. Instead, a predetermined measured volume is discharged as a spray, releasing a fixed amount of medication.  
           [0007]    Metered dose inhalers are available in several types. Most frequently, metered dose inhalers comprise a chamber into which a pressure resistant container (canister) is placed. The container is typically filled under super-atmospheric pressures with a product such as a drug dissolved in a liquefied propellant, or micronized particles suspended in a liquefied propellant. The container is fitted with a metering valve. The valve is movable from an outer (charging) position to an inner (discharging) position. A spring bias holds the valve in the charged position until forced to the discharge position. Actuation of the metering valve allows a metered portion of the canister content to be released, whereby the pressure of the liquefied propellant carries the dissolved or micronized drug particles out of the container and to the patient. A valve actuator also functions to direct the aerosol as a spray into the patient&#39;s oropharynx. Surfactants are usually dissolved in the aerosol formulation and can serve the dual functions of lubricating the valve and reducing aggregation of micronized particles. Examples of such metered dose inhalers are disclosed in U.S. Pat. Nos. 5,514,647 entitled “Metered Dose Inhaler”; and 5,622,163 entitled “Counter for Fluid Dispensers”; and U.S. patent application Ser. No. 09/241,010 filed Feb. 1, 1999 entitled “Metered Dose Inhaler Agitator” (commonly assigned), the disclosures of which are incorporated herein by reference.  
           [0008]    Representative of pharmaceutical formulations for use in metered dose inhalers are those described in U.S. Pat. No. 5,190,029. The metered dose inhalers for administering such pharmaceutical formulations are also well known as seen for example in the descriptions given in U.S. Pat. Nos. 3,361,306; 3,565,070; and 4,955,371 which are incorporated herein by reference.  
           [0009]    A wide variety of fluid dispensers are known and commercially available to dispense metered proportions of a contained fluid from containers. For example, U.S. Pat. No. 3,749,290 describes a trigger actuated dispensing pump assembled with a fluid container. Upon actuation, a measured proportion of the contained fluid is dispensed from the containers.  
           [0010]    “Pumping” type inhalers are known in the art. The device may be manually pumped (such as described in U.S. Pat. No. 5,284,132) or a pumping like cycle may be utilized. The medication may also be repeatedly released from a pressurized disposable canister to create repeated sprays or inhalations as needed.  
           [0011]    Proper use of these manually actuated devices requires that the spray be activated at the beginning of the inspiratory cycle, so that the medication is carried into the lungs rather than being deposited in the mouth or throat. If this actuation is not correctly coordinated with the inspiratory phase, the metered dose may be deported differently with each actuation acrd potentially compromise the therapeutics and safety of the product.  
           [0012]    There are numerous factors leading to poor coordination of actuation of the spray and the inspiration cycle. Included in those factors are the inherent limitations of the users (if any), such as impaired physical abilities associated with geriatric patients or the as-yet-undeveloped skills of children, or their inability of either group to comprehend the correct way to use the device. Recognizing the need for correct and accurately delivered doses in the asthmatics, COPD patients and, as with other patients with other respiratory illnesses, a reliable breath activated device would improve the quality of life for these afflicted people. Examples of breath-activated devices include U.S. Pat. No. 5,069,204 entitled “Inhaler” and U.S. patent application Ser. No. 09/567,352 entitled “An Inhalation Actuated Device”, the disclosures of which are herein incorporated by reference.  
         SUMMARY OF INVENTION  
         [0013]    It is therefore an object of the invention to provide an inhaler that is economical to manufacture, extremely easy to use, and delivers a metered dose of medicine, precise from dose to dose, in response to breath actuation and more particularly, in response to inspiration.  
           [0014]    It is therefore a still further object of the present invention to provide an inhaler that is breath-actuated with an option of removing an included dispenser/mouthpiece assembly that is capable of press and breathe dispensing of a medicament.  
           [0015]    To attain the objects described above, the present invention is directed to a pneumatically actuated, metered dose dispenser for an aerosol medication, The device has a housing defining a body portion into which the medicine-containing a canister is retained, and a mouthpiece for insertion into a patient&#39;s mouth. A mechanical lever with attached mouthpiece cover operates a compressor pump and after the device is pumped with a charge of compressed gas, maintained in a second chamber, a transfer valve is tripped by the vacuum formed when the user inhales from the device. This causes the compressed gas to enter a second chamber where the drug containing canister is maintained. This effects a depression of the canister valve stem, releasing the drug in an aerosol form. The release of the drug occurs at the same time as inhalation, insuring the delivery of a metered dose of medicine to the target location. In other words, the medicine is not mistargeted to the throat and upper mouth. The device of the present invention is relatively simple to operate, even by young children (6 to 12 years of age), and older patients as well, since inhalation initiates the dispensing of the drug.  
           [0016]    An additional embodiment of the present invention is the ability to remove a dispenser/mouthpiece assembly attached within the housing of the device. Upon removal, the assembly can be used as a press and breathe type dispenser. This is advantageous as a backup if the breath-actuation feature of the device fails. In common use, the dispenser/mouthpiece assembly could be removed to replace expended dispensers. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0017]    Embodiments of the present invention will be described with reference to the accompanying drawings in which:  
         [0018]    [0018]FIG. 1 is a cross-sectional view of the present invention showing the device in the at-rest position.  
         [0019]    [0019]FIG. 2 is a cross-sectional view of the present invention showing the device in the cocking position.  
         [0020]    [0020]FIG. 3 is a cross-sectional view of the present invention showing the device in the fired position.  
         [0021]    [0021]FIG. 4 is an exterior view of the present invention showing the device in the at-rest position.  
         [0022]    [0022]FIG. 5 is an exterior view of the present invention showing the mouthpiece cover removed.  
         [0023]    [0023]FIG. 6 is an exterior view showing the device in a cocked position.  
         [0024]    [0024]FIG. 7 is an exterior view of an alternative embodiment of the present invention showing detachment of a mouthpiece/canister assembly from the device. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0025]    Turning now more particularly to the drawings, in FIG. 1 there is provided an inhalation actuated device  10 , which comprises a housing  12  with a mouthpiece/canister assembly  14 . Inhalation actuated device  10 , depicted in FIG. 1, includes a detachable mouthpiece/canister assembly  14 ; however, the mouthpiece  16  and associated actuation components may be manufactured as part of device  10 .  
         [0026]    When the mouthpiece/canister assembly is operated, the canister stem  22  is impinged against surface  26 , in response to displacement of the canister during a pressure actuation. The medicine is discharged from the canister stem as an aerosol. The nozzle  24  directs the spray outward through the mouthpiece  16 .  
         [0027]    In device  10 , the first chamber  20  is defined by an outer wall  28 , an upper surface  30  and a partitioning wall  32 . A second chamber  34  is formed on the other side of partitioning wall  32 , defined by the partitioning wall  32 , upper surface  30 , and outer wall  36 . A movable piston  38  provides the lower surface of the second chamber  34 . The volume of the second chamber is variable with respect to the location of the piston  38  within the chamber (shown in an at-rest position in FIG. 1). In operation, the piston is used to compress an initial volume of gas into a smaller one, thereby increasing the pressure of the gas. The energy stored in the compressed gas is used to effect the discharge of the medicine from the canister, as will be discussed.  
         [0028]    There is a third chamber  40  in device  10 , defined by the outer wall  28 , upper surface  30 , transfer valve cover  42 , and airway cover  44 . The third chamber  40  is a replenishable reservoir used to provide air to the second chamber  34  when resetting the movable piston  38 , as will also be discussed.  
         [0029]    The upper portion of the piston  38  is attached to lower piston support  46  forming compression piston assembly  48 . Connecting link  50  is affixed to the compression piston assembly at first end  52 . The second end  54  of the connecting link  50  is affixed to a first end  55  of the cocking lever  56 . The cocking lever  56  is pivotally mounted about axial attachment rod  58 , which fixedly attaches the cocking lever  56  to the housing. The second end  60  of the cocking lever  56  is affixed to the mouthpiece cover  18  at connecting pivot  62 .  
         [0030]    In operation, the cocking lever  56  pivots between an at-rest position and a charging position. When the inhalation device  10  is in an at-rest position, the cocking lever  56  rests in proximity to the underside  63  of the device and mouthpiece cover  18  protects mouthpiece  16 .  
         [0031]    Piston  38  is dimensioned to fit snugly against the inner walls of the second chamber  34 , so that when the piston is moved into a cocked position, the fluid (gas, i.e. air) within the second chamber is compressed. The piston is provided with U -cup seals  64  which are situated within openings  66  in the piston  38 , to prevent blowby leakage of compressed fluid around the sides of piston. In the-place of the piston seals, a rolling diaphragm seal, or a bellows-type system can also be used.  
         [0032]    The upper surface  30  in the second chamber  34  also has a passage  67  in which an elastomeric umbrella check valve  68  is fitted. When the cocking lever  56  is moved towards the body of the device the connecting link  50  pulls the compression piston  38  downward. This action draws ambient air from the mouthpiece  16  or apertures  103  and  104  the third chamber  40  through passage  67 , past the umbrella check valve  68  and into the second chamber  34 .  
         [0033]    The upper surface  30  in the second chamber  34  also has an aperture  69  into which a high pressure orifice  70  is fitted. As shown; in FIG. 2, when the cocking lever  56  is moved away from the mouthpiece  16  and toward the body of the device, the connecting link  50  pushes the compression piston  38  upwards. Cocking lever  56  and connecting link  50  are configured to toggle, so as to maintain the compression piston  38  near its upwardmost position prior to triggering. A toggle stop  71  is secured to partitioning wall  32 , preventing over-action of the cocking lever  56 .  
         [0034]    The upward motion of the compression piston  38  pushes compressed fluid past the high pressure orifice  70  and against elastomeric diaphragm  72 . The elastomeric diaphragm  72  is clamped at its periphery between the transfer valve cover  42  and the upper surface  30  of the housing to form an air tight seal. As shown, elastomeric diaphragm  72  borders space  73  and is provided as part of a fluid pathway  74 . When the pathway  74  is open, the pathway  74  and second chamber  34  are in fluid communication with each other. Also provided is a transfer port  76 , which is an orifice that is in fluid communication with chamber  20   a , a subchamber of chamber  20 . Chamber  20   a  is positioned between surface  30  and actuation piston  78  and is formed by the movement thereof. When the pathway  74  is open, the pathway  74  and chamber  20   a  are also in fluid communication with each other, and the compressed fluid can flow from the second chamber  34  to the chamber  20   a , expanding the size of chamber  20   a  (more clearly shown in FIG. 3).  
         [0035]    The actuation piston  78  is provided with U-cup seals  80 . Prior to triggering, piston  78  is positioned at the upper end of chamber  20   a . The lower portion of piston  78  abuts against canister  81 .  
         [0036]    There is little, if any, open volume in the space between the lower part of the upper surface  30  and the actuation piston  78 . The actuation piston  78  fits snugly against the housing wall  12  and the partition wall  32 , in order to form a seal that prevents leakage of the compressed fluid when it is released from the second chamber. Note that the actuation piston (and for that matter the compression piston) may take on a variety of forms including rolling diaphragms, bellows, etc. or other means suitable for purpose.  
         [0037]    Above the diaphragm  72  there is a seat  82  that passes through the transfer valve cover  42  and presses against the diaphragm  72 , providing a counterforce against the compressed air in the second chamber  34 , insuring that the diaphragm is sealed.  
         [0038]    At its top  82 A, seat  82  engages an end of lever  83  which assists in triggering the diaphragm  72 . The opposite end of lever  83  engages a compound diaphragm  86 . The opposite side of diaphragm  86  is open to ambient air by way of aperture  88 . Lever  83  is allowed to pivot about pivot point  84 .  
         [0039]    Biasing spring  98  serves to maintain diaphragm  72  in a sealed state prior to triggering and after the fluid has been compressed in chamber  34 .  
         [0040]    The preferred embodiment described above is operated in the following manner. After the mouthpiece/canister assembly  14  has been loaded into the first chamber  20 , the user flips the mouthpiece cover  18  away from its protecting position on the mouthpiece  16 , such that the mouthpiece cover  18  is aligned with the cocking lever  56 . The user then moves the cocking lever  56  toward the device and outward from the housing, as shown in FIG. 2. When the cocking lever is moved in this fashion, the connecting link  50  pushes the compression piston  38  upward. By forcing the compression piston  38  upward, volume in the chamber is reduced and the fluid in the chamber  34  is compressed.  
         [0041]    As shown in FIG. 3, when the user inhales through the mouthpiece  16 , a vacuum is created inside the device (specifically, in the first and third chambers  20  and  40  and in the upper space  73  above fluid pathway  74  through vent orifice  100 ). The produced vacuum rapidly creates a differential pressure across the diaphragm  72  and compound diaphragm  86 . For diaphragm  72 , a threshold value is instantly exceeded at which point the biasing spring  98  can no longer keep the diaphragm in the sealed position. As part of this, the vacuum created causes diaphragm  86  to be sucked in to a certain degree causing lever  83  to pivot about pivot point  84  placing an upward force on seat  82 . This in conjunction with the pressure differential created across diaphragm  72  causes it to snap open. Once open, the compressed fluid exits the second chamber  34 , traverses the fluid pathway  74 , and enters the first chamber  20  through transfer port  76 , applying pressure to the actuation piston  78  and expanding chamber  20   a . The force acting on the actuation piston  78  overcomes the return spring (not shown) in the canister stem  22 , moving the canister  81  and/or stem to cause the dispensation of the medicine as an aerosol. The medicine is dispensed through the nozzle  24  and mouthpiece  16 .  
         [0042]    Note that when the user inhales, ambient air is drawn through apertures  103  and  104  allowing the user to breathe in whilst creating the pressure differential or vacuum signal that triggers the device. Accordingly, these apertures  103 ,  104  may be so sized so as to regulate the pressure drop within the device upon inhalation of the user and thus control the point at which the device is triggered. In addition, orifices  103 , 104  provide fresh air to chamber  34  via chamber  20 , pathway  28 , chamber  40 , and pathway  67 .  
         [0043]    A bleed orifice  105  in the crown of the actuation piston  78  slowly bleeds off the compressed air contained between the upper surface  30  and the piston  78 , permitting the canister return spring to push the piston back to its original position, without user intervention. This prevents canister leakage that can occur if the valve stem remains depressed for prolonged periods. Moreover, as the pressure equalizes throughout the interior of the device, the biasing spring  98  returns the diaphragm  72  to the sealed position and lever  83  repositions itself.  
         [0044]    The dwell time and air bleeding function of bleed orifice  105  is implemented by using a porous (7 μm) membrane inserted into a bore of actuation piston  78  where the bleed orifice is located. Using a porous membrane minimizes the chance that the bleed orifice becomes blocked or obstructed by debris.  
         [0045]    It should be evident to the skilled artisan that inhalation and discharge of the medicine from the container is very quick, on the order of about 200 milliseconds, which insures that the inhalation of the medicine commences at the beginning of the inhalation, insuring delivery of the drug to a greater degree of targeted surface area, which ordinarily is the lungs, than is usually possible.  
         [0046]    Turning now more particularly to FIGS.  4 - 6  there is shown the exterior of the inhalation device  10  and its operation as it would appear to the user. FIG. 4 depicts the inhalation device  10  in an at-rest position. Mouthpiece  16  is protected by mouthpiece cover  18 , with cocking lever  56  resting on the underside  63  of housing  12 . The underside  67  of housing  12  may be notched to conformingly fit cocking lever  56 . In FIG. 5, mouthpiece cover  18  is flipped in a downward direction  110  with mouthpiece  16  uncovered and cocking lever  56  ready for cocking.  
         [0047]    In FIG. 6, cocking lever  56  is shown in its cocked position, after completion of movement in direction  112 . Inhalation device  10  is now ready for use.  
         [0048]    In an alternative embodiment, mouthpiece/canister  14  is removable from inhalation device  10 . As shown in its detached position in FIG. 7, mouthpiece/canister assembly  14  is detachable by means of a bayonet-type locking mechanism  112 , which upon rotation  114  releases the mouthpiece/canister assembly  14 . With cocking lever  56  in a firing position, mouthpiece/canister assembly  14  can be removed. With mouthpiece/canister assembly  14  removed, canister  81  can be easily changed or mouthpiece/canister assembly  14  can be used as a separate press and breathe type inhaler. When inserted, locking mechanism  112  rotates and interlocks with a slot  118  for securing the mouthpiece/canister assembly. In the at-rest position, cocking lever  56  and mouthpiece cover  18  provide additional securing of the mouthpiece/canister assembly within the inhalation device  10 . Of course, other means of securing the mouthpiece/canister assembly  14  to the inhalation device  10  suitable for the purpose will be apparent to the skilled artisan.  
         [0049]    The objects and advantages of the present invention are realized in accordance with the disclosure set forth above. Although preferred embodiments have been described in detail, the scope of the present invention should not be limited by this disclosure, but rather its scope should be determined by the appended claims.

Technology Category: 1