Abstract:
A dose selective breath actuated inhaler including a meterless canister storing a pressurized medicament, and a vacuum actuated release, where application of a vacuum to the inhaler initiates a release of the medicament in the canister. The inhaler includes a mechanism for dialing a proper dose of pressurized medicament, a computer for generating a plurality of signals including a solenoid trigger signal, and a solenoid which upon receipt of a solenoid trigger signal actuates a solenoid arm to end the release of the medicament from the canister.

Description:
CROSS-REFERENCE SECTION TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of U.S. Provisional Patent Application No. 60/868,152, filed Dec. 1, 2006, which is hereby incorporated by reference in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to a metered dose inhaler and in particular to a metered dose inhaler that uses a variable timer for administration of desired amounts of drug from a meterless aerosol canister depending upon a patient&#39;s need. 
       BACKGROUND OF THE INVENTION 
       [0003]    In an effort to provide for a non-invasive means of administering insulin and other systemic drugs to patients, and thereby eliminate the need for syringes, aerosolized formulations have been theorized. 
         [0004]    Heretofore, the studies and experiments in the pulmonary delivery of insulin have suffered from poor reproducibility of the dose to be inhaled. Typically, known inhaler devices utilize a metered dose canister that dispenses a discrete quantity of drug each time the valve is depressed. Known dry powder devices, for example, typically employ small reservoirs for each drug dose whereby the reservoirs are individually emptied into the inhaled air stream at each actuation. Dry powder inhalers are also generally less precise and robust as compared to liquid metered dose inhalers. Importantly, both dry powder inhalers and metered dose inhalers for the delivery of liquids provide only a specific dose amount. Users that require more of a drug than is available in one dose may be required to go through the actuation sequence multiple times in order to receive the proper amount of drug. Due to the limitation on dosage amount in these known inhalation devices, a user may not even be able to dose properly according to the precise amount needed. 
         [0005]    Aside from diabetes and its treatment with insulin, a number of other diseases require the active participation and understanding of the patient to provide for accurate, and therefore, effective dosing. Examples of such diseases are chronic obstructive pulmonary disease (COPD), asthma, and other respiratory problems. 
         [0006]    Thus, there is a need for a device and method providing for the effective and variable dosing for a patient to insure that effective amounts of drug are received at the desired time. There is a further need that such a device is user-friendly providing adequate administration of the drug preferably in a single inhalation. 
         [0007]    The present invention endeavors to overcome the problems of the prior art and provide a non-invasive device and methodology for delivery of drugs that produces repeatable and variable/controlled dosage amounts of a drug to the patient substantially without the need for complex circuitry having high-energy demands. 
       SUMMARY OF THE INVENTION 
       [0008]    One aspect of the instant invention is directed to a dose selective breath actuated inhaler including a meterless canister storing a pressurized medicament, and a vacuum actuated release, where application of a vacuum to the inhaler initiates a release of the medicament in the canister. The inhaler also includes a computer for generating a plurality of signals including a solenoid trigger signal, and a solenoid that upon receipt of a solenoid trigger signal actuates a solenoid arm to end the release of the medicament from the canister. 
         [0009]    According to another aspect of the present invention, a dose selection device is used with a metered dose inhaler that enables a user to dial in the appropriate dose and thereafter initiate release of the medicament, inhaling until the user is signaled to stop inhaling (e.g., when the selected dose has been fully administered). 
         [0010]    Another aspect of the instant invention is drawn to a method of administering a substance to a human patient by inhalation including providing an inhaler with a meterless canister containing the substance, selecting a dose of the substance by manipulating a dose-selector on the inhaler, and inhaling the selected dose. 
         [0011]    Still another aspect of the instant invention is a method of administering a substance including steps of providing an inhaler including a meterless canister storing a pressurized medicament, a vacuum actuated release, a computer for generating a plurality of signals including a solenoid trigger signal, and a solenoid having a solenoid arm. The method also includes steps of applying a vacuum to a mouthpiece portion of the inhaler to trigger release of the medicament in the canister, running a clock function from the time release of the medicament begins, and generating a solenoid signal at the completion of the clock function, the solenoid signal actuating the solenoid arm to cease release of the medicament from the canister. 
         [0012]    Other embodiments of the present invention will be described in greater detail below. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0013]    Further characteristics, features, and advantages of the present invention will be apparent upon consideration of the following detailed description of the invention taken in conjunction with the following drawings, and in which: 
           [0014]      FIG. 1  is a perspective view of an inhaler according to one aspect of the present invention; 
           [0015]      FIG. 2  is a perspective view of the inhaler of  FIG. 1  in the cocked position; 
           [0016]      FIG. 3  is a perspective view of the inhaler of  FIG. 1  showing its two-piece construction with the insertion of a drug canister; 
           [0017]      FIG. 4  is a cross-sectional view of an inhaler according to one aspect of the present invention in the stored position; 
           [0018]      FIG. 5  is a cross-sectional view of an inhaler according to one aspect of the present invention in the cocked position; 
           [0019]      FIG. 6  is a cross-sectional view of an inhaler according to one aspect of the present invention at the point when the user begins to inhale; 
           [0020]      FIG. 7  is a cross-sectional view of an inhaler according to one aspect of the present invention during administration of the drug; 
           [0021]      FIG. 8  is a cross-sectional view of an inhaler according to one aspect of the present invention following administration of the drug; 
           [0022]      FIG. 9  is a cross-sectional view of an inhaler according to one aspect of the present invention following administration and closure of the cover to return the device to its stored position; and 
           [0023]      FIG. 10  is a schematic diagram of an electrical circuit according to one aspect of the instant invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0024]      FIG. 1  shows a dose selective breath actuated inhaler according to one aspect of the present invention. The dose selective inhaler  100  includes a dial  102  which may be turned by the user to alter the dose to be administered by the inhaler  100 . The dose selective inhaler  100  also includes a (lose administration indicator, for example, a LED (light-emitting diode) inhalation light  104 , which indicates to the user when the medication is being dispensed. The inhalation light  104  is just one example of a structure that may be used to indicate to a user when the user has begun to inhale and when to stop inhaling in order to receive the proper dose. Other dose administration indicators, whether visual, auditory, or tactile (e.g., a vibrating device, which may be important for a blind patient) may be used. The inhaler  100  is a breath-actuated inhaler where the patient&#39;s inhalation triggers the medication release. The inhalation light  104  turns on upon cocking of the device as shown in the progression from  FIG. 1  to  FIG. 2 , and continues to be illuminated as the device administers a dose, turning off once the dose has been fully administered to signal to the user that they can cease inhaling. The breath-actuated inhaler  100  of the present invention is described in detail below. Importantly, other devices that incorporate a meterless canister and contain the necessary connectivity between a dose selection dial  102 , a computer  126 , and an inhalation light  104  or other means for indicating to the patient to continue or discontinue inhaling while the dose is being administered, can be used to administer drugs using the dose selection technology of the present invention. 
         [0025]    Referring again to  FIG. 1 , the inhaler  100  includes a units-remaining indicator  106 . As can be readily understood by those of skill in the art, in a device that has variable dosing characteristics, accounting for the volume of medicament already administered and the amount remaining in the device is important so that the patient is never in a situation where there are no doses remaining when they are in need of the medication. In practice, doses of medication are not counted, (as in the traditional dose counters) rather International Units or IU&#39;s are counted. As a result, when a patient determines that they require a dose of 70 IU&#39;s as shown in  FIGS. 1 and 2 , the user twists the dial  102  until the dose-setting indicator  108  reads  70 . The dose-setting indicator  108  may be an LCD, but may also be a simple printed indicator, which is uncovered as the dial  102  is rotated. The user then rotates the cover  110  to expose the mouthpiece  112 . At this position, the inhaler  100  is ready to administer a dose of 70 IU&#39;s to the patient. Upon administration of the 70 IU&#39;s, the value will be subtracted from the number of IU&#39;s indicated as remaining in the inhaler by units-remaining display  106 . 
         [0026]      FIG. 3  shows the inhaler  100  opened into its two component parts: a base  114  and a cap  116 . The cap  116  can be joined to the base  114  by any suitable means known to those of skill in the art. As shown in  FIG. 3 , tabs  118  are formed on the cap  116  and include projections  120  extending outwardly therefrom. The projections  120  fit into slots  122  formed in the base  114 . The slots  122  may, as shown, have an L-shape allowing the cap  116  to be rotated into the slots  122  and secured to the base  114 . Situated in the base  114  is a canister  124 , preferably a meter-less canister, which is a canister that, upon actuation, will continue to dispense the pressurized medication contained therein until either the entire canister is emptied, or the pressure causing the actuation of the canister is released. 
         [0027]      FIG. 4  shows a cross sectional view of a dose selective breath actuated inhaler  100  according to one aspect of the instant invention. The inhaler  100  includes a meterless canister  124 . As shown in  FIG. 4  the inhaler  100  is in the stored or at-rest position. The mouthpiece  112  is covered by a hinged cover  110 , which, as will be discussed, also acts as the cocking mechanism for the inhaler  100 . 
         [0028]    The inhaler  100  shown in  FIG. 4  also includes a timing and display control or computer  126 . The computer  126  is electrically connected to a solenoid  128  and a battery  130 , as well as the units-remaining display  106 , the inhalation light  104 , an actuation sensor switch  132 , a cocking switch  142 , and preferably the dose-setting indicator  108 . The computer and its interconnection to various components are outlined in detail below with respect to  FIG. 10 . 
         [0029]    The cap  116  contains a spring  134 , which rests in a spring release mechanism  136 . The spring release mechanism rests on the canister  124 . The spring release mechanism  136  includes two concentric cups  138  that are in vertical sliding engagement with one another and a spring biased collapsible knuckle  140 . The spring biased collapsible knuckle  140  prevents the two cups  138  from collapsing into each other under the pressure applied by the spring  134  when in its extended position as shown in  FIG. 4 . Upon application of pressure in a direction perpendicular to the longitudinal dimension of the spring biased knuckle  140 , the spring biased knuckle collapses, as shown in  FIG. 8 . The collapse of the spring biased knuckle  140  will be described in greater detail below. 
         [0030]    The cap  116  also contains the cocking switch  142  that provides an electrical signal to the computer  126  when it senses that the inhaler has moved from the at-rest position shown in  FIG. 4  to the cocked position shown in  FIG. 5 . When the inhaler  100  is in its at-rest position, the switch  142  is depressed. When the inhaler  100  is moved to the cocked position as shown in  FIG. 5 , the switch  142  is released. A further feature of the cap  116  is an orifice  170  that allows for the entry of air from the atmosphere into the inhaler  100  which assists in dispersing the medicament and providing a volume to be inhaled with the medicament by the user. 
         [0031]    The cap  116  includes a dial  102 . The dial  102  is connected either mechanically, or preferably electrically to computer  126 . By this connection, rotation of the dial  102  alerts the computer  126  of the size of the dose, that is, the number of IU&#39;s to be administered. The computer  126  calculates a time period for dose administration based on the spray rate of the canister  124 . As a result the user is able to adjust the size of a medicament dose and the device indicates to the user, via the inhalation light  104 , how long to continue inhaling until the full dose has been administered. 
         [0032]    The inhaler  100  includes a release mechanism that includes a rocker  144 , a cam  146 , a follower  148 , and a diaphragm  150 . In  FIG. 4 , the cam  146  is connected on one end to the diaphragm  150 , and is held in place in the inhaler  100  by a pin  152  on the other end. The cam  146  also includes a lip  154  which is formed on the end of the cam  146  connected to the pin  152 . The follower  148  is connected to the rocker  144  by another pin  156 ; the follower  148  is free to rotate about the pin  156 . In addition, the follower  148  has a lip  158  which interacts with the lip  154  as bill be discussed below. 
         [0033]    As mentioned above,  FIG. 4  shows the inhaler  100  in the at-rest position. In this position the spring  134  is in a less biased state and the cups  138  are spread apart from one another by the spring biased knuckle  140 . The cocking switch  142  is depressed and the follower  148  rests on the cam  146 . 
         [0034]    As shown in  FIG. 5 , the cover  112  is open exposing the mouthpiece  110 . The movement of the cover  112  causes a rod  160  having a head  162  to compress the spring  134  against the top cup  138 . The movement of the head  162  also releases the cocking switch  142 . The release of the cocking switch  142  sends a signal to the computer  126  indicating that the inhaler is now cocked and ready to administer drug. In one preferred embodiment it is the release of the cocking switch  142  that signals the computer  126  to change from a sleep-mode to an on-mode. In the sleep-mode, in a preferred embodiment, only the units-remaining display  106  is illuminated and drawing electrical power. Upon entering the on-mode the computer  126  begins to function, calculating the time for actuation of the inhaler based on the dialed-in dose and the ambient temperature within the housing, the solenoid  128  is powered, the inhalation light  104  is powered, and the inhalation switch  132  is monitored. As described herein, the cocking switch  142  is a normally closed switch, that when the pressure of the spring is removed therefrom closes the electrical circuit connecting the cocking switch  142  to the computer  126 . 
         [0035]    In accordance with another embodiment of the present invention, the computer  126  can be turned on to the on-mode by manual depression of a switch (not shown) on the exterior of inhaler  100 . 
         [0036]    In  FIG. 6 , the patient begins to inhale. The patient&#39;s inhalation causes a vacuum in the interior of the inhaler. This vacuum causes the diaphragm  150  to deform in the direction of the user&#39;s mouth, which is the origin of the vacuum. The deformation of the diaphragm  150  is assisted by holes  164  formed in the base  114  which allow air to enter the base  114  of the inhaler  100  on a backside of the diaphragm  150 . The air that enters the inhaler at the back side of the base  114  is of a higher pressure than the vacuum created internally in the inhaler  100 , which thereby causes the deformation of the diaphragm  150 . The movement of the diaphragm  150  causes movement of the cam  146 . e.g., rotation, about the pin  152 . The movement or the cam,  146  causes the lip  154  formed on the cam  146  to put pressure oil the lip  158  of the follower  148 . The follower  148  begins to rotate about the pin  156  connected to the rocker  144  because the rocker is held in place by the canister  124 . As the diaphragm  150  continues to expand, lip  154  formed on the cam  146  forces the follower  148  off of the cam  146  as shown in  FIG. 7 . 
         [0037]    Upon release of the follower  148  from the cam  146 , the rocker  144  is free to pivot. With respect to  FIG. 7  the rotation is in a clock-wise direction. The movement of the rocker  144  releases the canister  124  and allows the spring  134  to expand forcing the canister  124  to move in the direction of the base  114 . The canister  124  includes a spring biased stem  166  connected to a valve (not shown) in the canister  124 , initially, the spring pressure asserted by the spring  134  overcomes the spring internal to the canister  124 , causing the valve to open and release the pressurized medicament from the canister. 
         [0038]    The expansion of the spring  134  is enabled by the release of the rocker  144 . The spring  134  acts on the top cup  138  on one side and against the head  162  of the rod  160 . The head  162  of the rod  160  prevents the expansion of the spring  134  in the direction of the cap  116 . Because the cups  138  are prevented from collapsing by the spring-biased knuckle  140 , the spring  134  causes the canister  124  to move downward releasing the medicament as described above. In addition, this movement triggers the actuation sensor switch  132 . This triggering sends a signal to the computer indicating that dispensing of medicament has begun. The spring  134 , as shown in  FIG. 7 , is in a less biased position than as shown in  FIG. 5  or  6 . The closure of the actuator sensor switch  132  sends a signal to the computer  126  to begin running of a clock function within the computer  126 . The clock function as will be described below continues sending power to illuminate the inhalation light  104  for a time specified depending on, for example, the dose to be administered. Upon the running of the clock for the time specified, the inhalation light  104  will turn off signaling to the user that they can stop inhaling, as the complete dose has been administered by the inhaler  100 . Other functions of the actuator sensor switch  132  and the computer  126  are discussed below with respect to  FIG. 10 . 
         [0039]      FIG. 8  shows the inhaler  100  following completion of dispensing a dose to a user. As described above with respect to  FIG. 7 , upon movement of the canister  124  downward by the release of the rocker  144 , the canister  124  closes the actuation sensor switch  132  and begins to dispense medicament. This triggering of the actuation sensor switch  132  sends a signal to the computer  126  to run a clock function. The duration of the clock function is calculated by the computer  126  based on the number of IU&#39;s to be administered and the spray rate of the canister  124 . Upon the completion of clock function, the computer  126  sends a signal to the solenoid  128 . This signal causes the solenoid  128  to extend the solenoid arm  129  and collapse the spring biased knuckle  140 , as shown in  FIG. 8 . The solenoid arm  129  accesses the spring-biased knuckle  140  via slots (not shown) in one side of the cups  138 . This collapsing of the knuckle  140  allows the pressure of the spring  134  to collapse the slidingly engaged cups  138 . As a result, the spring  134  extends in the vertical direction. At a predetermined extension offspring  134 , the spring force generated by the spring  134  is less than the spring force of the internal spring in the canister  124  which acts on the spring biased stem  166 . When the spring force of the internal spring (not shown) in the canister  124  is greater than the force of spring  134 , the canister  124  moves vertically upward, the internal canister valve (not shown) closes, and administration of the dose ends. As described above, in the preferred embodiment the inhaler  100  uses a meterless canister, which permits dispensation from the inhaler  100  of as little or as great of a dose as required by the user. 
         [0040]      FIG. 9  shows the return of the inhaler  100  to the at-rest position after completion of dose dispensation to a user. The cover  112  is closed covering the mouthpiece  110 . The movement of the cover  112  acts on the rod  160  to move the canister  124  in the direction of the cap  116 . The movement of the rod  160  releases some of the spring pressure created by the spring  134  and allows the spring in the spring biased knuckle  140  to return the knuckle to its extended position which simultaneously causes the cups  138  to move distally away from each other. The head  162  contacts the cocking switch  142  and depresses it sending a signal to the computer  126 . The rocker  144  is returned to its at-rest position, which in turn returns the follower  148  onto the cam  146 , which has also returned to its at-rest position once the pressure inside the inhaler and the pressure out side the inhaler have equalized following administration of the dose. This may be assisted by making the diaphragm  150  of a material that is biased in the direction away from cam  146 . Preferably, the diaphragm is made of an elastomeric material. The movement of the canister  124  also removes the pressure applied to the actuator sensor switch  132 . Either the release of the actuator sensor switch, or the depression of the cocking switch can be used to return the computer  126  to a sleep mode. Alternatively, the computer can be shut off by pressing an “off” button (not shown) on the inhaler  100  exterior or by releasing an “on” button (not shown) on the inhaler  100  exterior. 
         [0041]    The computer  126  will now be discussed with respect to  FIG. 10 . The computer  126  is connected to the battery  130 , which provides electrical power for the inhaler  100 , and a solenoid power supply  127  which supplies power to the solenoid  128 . The battery  130  also supplies power to the electrical components of the inhaler  100  including the inhalation light  104 , the units-remaining display  106 , the dose-setting indicator  108 , and the switches, as well as the computer  126 . As will be understood by one skilled in the art, the computer  126  can be programmed to receive numerous inputs and perform various functions. 
         [0042]    First, according to one embodiment of the present invention, the computer  126  receives input from the dose selector  102 . By rotating the dose selector  102 , an electrical contact (not shown) on the cap  116  is contacted by an electrical contact (not shown) in the dial of the dose selector  102  forming a circuit. The parameters of this circuit create the dose selector signal  202  which is supplied to the computer  126  and is used to determine the time period for a clock signal. As will be discussed below, the clock signal is used to provide the time period for illuminating the inhalation light  104  following triggering of the inhaler  100  to release a dose, as well as the time period for supplying power to the solenoid  128  that ultimately ceases the dose administration. This dose signal  202  also determines the number of IU&#39;s to be deducted from the units-remaining display  106 . 
         [0043]    Another input received by the computer  126  is the cocking switch input  242 , which is received once the inhaler has been cocked as shown in  FIG. 5 . In one embodiment this may be a normally closed switch, that when the pressure applied by the head  162  of the rod  160  removed, returns to its closed position to complete the circuit. This may be, for example, to act as an on/off switch for the inhaler  100  so that power is conserved at all times except when the device is cocked and ready to administer the drug. As a result, when the inhaler  100  is returned to the at-rest position as shown in  FIG. 9 , following administration of the drug, the power to the inhaler is shut off except for the display of the IU&#39;s remaining  106 , which is preferably constantly maintained. 
         [0044]    The computer  126  also receives an actuation sensor signal  232  from the actuation sensor switch  1332 . When a user inhales on the mouthpiece  110 , the release of a dose is triggered (as discussed above), which causes the canister  124  to move in the direction of the base  114  and close the normally open actuation sensor switch  132 . The closure of this switch sends a signal to the computer  126  to start a clock signal that illuminates the inhalation light  104  by supplying a signal  204 . Other means of indicating to the user how long the user must inhale in order to receive the proper dose (i.e. other dose administration indicators, whether visual, auditory, or tactic) may also be used, in which case the computer  126  is programmed so that the clock signal triggers the dose administration indicator. Prior to the user&#39;s inhalation, the computer  126  has performed a calculation based on the dose selector signal  202 . Once the actuation sensor switch  132  is switched on, the inhalation light  104  will be turned on signaling to the user to continue inhaling. Upon expiry or the running of the clock to zero, the computer  126  opens the circuit to the inhalation light  104  extinguishing the light and signaling to the user to stop inhaling. At the same time, signal  228  is sent to the solenoid  128  to actuate the solenoid arm  129  to stop the release of the medicament. 
         [0045]    The actuation signal  232  also triggers calculation of the number of IU&#39;s being dosed, and the computer  126  deducts that amount from the units-remaining display  106 . Alternatively, the computer  126  can be configured to deduct the amount of units-remaining from the display  106  upon closure of the mouthpiece cover, which returns the inhaler  100  to its at-rest position as shown in  FIG. 9 . 
         [0046]    The computer  126  also receives an input from a temperature sensor  168  that provides a temperature signal  168 . As will be appreciated by those of skill in the art, the temperature of the inhaler, which is generally near ambient, will affect the dispensation of a pressurized medicament. The higher the temperature, the higher the pressure that will be developed by the expansion of the propellant inside the canister  124 , which affects the timing of release of the medicament, because medicament at a higher pressure will release a greater volume in a set period of time than when it is at a lower pressure. Accordingly, temperature may advantageously be factored into the calculation of the clock function of the computer  126 . 
         [0047]    Advantageously, as discussed above, the computer enables the user to set their desired dose and then have the inhaler indicate the number of IU&#39;s remaining after each administration so that each patient can manage medication usage and receive the proper amount of medication dependent upon the patient&#39;s needs. As will be understood by one of ordinary skill in the art, the computer  126  of the present invention can be configured and programmed to perform a wide range of functions not limited to the functions described herein. 
         [0048]    Another aspect of the present invention is the use of the dosage triggering and timing mechanism described above in a breath actuated nasal drug delivery device as described in commonly assigned and co-pending U.S. patent application Ser. Nos. 11/160,493 and 11/418,527, the contents of which are incorporated herein by reference. 
         [0049]    The type of medicament used therein does not limit the present invention. Examples of drugs that can be used with the present invention are short-acting β2-agonists such as albuterol and salbutamol, which provide quick relief from acute asthma symptoms. Long-acting β2-agonists such as salmeterol and formoterol are used to control asthma symptoms over a longer period of time. Another class of drugs contemplated in the present invention are anticholinergics such as ipratropium bromide, which helps prevent bronchospasms in COPD patients. Corticosteroids, such as budesonide, fluticasone and triamcinolone acetonide, are often used in asthma treatment for their anti-inflammatory effects. The instant invention can be used to deliver any of these drugs, as well as any combination thereof, such as for example, flutiform, a combination of fluticasone (a corticosteroid) and formoterol. 
         [0050]    Typically active ingredients in the formulations used in an inhaler as shown in  FIG. 1  are readily made as suspensions or solutions with highly volatile propellants, such as for example. HFA-134(a) or HFA-227. Common pressurized aerosolized formulations well known in the industry are contemplated in this invention, and it will be understood by one of skill in the art that this includes formulations containing various excipients and stabilizers, such as for example, oleic acid, aspartame, water, ethanol, ethanoic acid, phosphatidyl choline, etc. 
         [0051]    While certain formulations and diseases have been specifically discussed herein, the present invention is not so limited and may be used with any formulation deliverable with a metered dose inhaler. 
         [0052]    Thus by the foregoing examples, the objects and advantages of the present invention are realized, and although preferred embodiments have been disclosed and described in detail herein, its scope and objects should not be limited thereby; rather its scope should be determined by that of the appended claims.