Abstract:
An apparatus for use in conjunction with a metered dose inhaler which includes a novel valve system to aid in the delivery of aerosolized medicament to a subject. The apparatus also includes a novel rotational flow generator to aid in the useable delivery of said medication and avoid its loss either in the apparatus or by non-useful delivery to said subject.

Description:
CROSS REFERENCE TO PRIOR APPLICATIONS 
       [0001]    This application is a Continuation Application of U.S. patent application Ser. No. 12/332,976, filed Dec. 11, 2008, which is a Continuation Application of U.S. patent application Ser. No, 10/943,542, filed Sep. 17, 2004, which is a Continuation Application U.S. patent application Ser. No. 10/137,007, filed May 2, 2002, all of which are incorporated herein by reference. A claim of priority to all, to the extent appropriate is made. 
     
    
     BACKGROUND 
       [0002]    The present invention is directed to apparatus for delivering aerosol medicament to a subject in need of the medicament. Delivery systems start with an aerosol-generating device. One common example of such devices is a pressurized metered dose inhaler (MDI). MDIs use pressurized gases to disperse medicament as tiny particles or droplets for delivery to the subject. By depressing the MDI, a known quantity of gas, and thereby of medicament, is ejected from the MDI. MDIs have been used with various types of diverse apparatus, in attempts to improve the delivery of this known quantity of medicament to the subject. Some problems associated with the delivery of medicament in an aerosol form include, but are not limited to, wastage of medicament in the delivery apparatus, delivery at too high speeds so that medicament sticks to the back of the subject&#39;s throat or is inhaled into the subject&#39;s sinuses rather than being received into the lungs, ejection of medicament out of the apparatus towards a subject without inhalation thereby, and ejection of medicament from the MDI upon exhalation by the subject into the apparatus prior to inhalation. 
       SUMMARY OF THE INVENTION 
       [0003]    In one aspect, the present invention provides a mouthpiece with a valve for controlling the delivery of aerosolized medicament to a subject. The mouthpiece includes a housing that defines a passage through which the medicament flows to the subject. The housing has a one-piece valve system that permits passage of medicament aerosol to the subject during inhalation, but does not permit the passage of the subject&#39;s breath in the upstream direction during exhalation, with the exhaled breath being expelled through an opening in the sidewall of the housing. 
         [0004]    Another aspect of the present invention combines this mouthpiece and valve system with a holding chamber, which is disposed between the mouthpiece and the source of aerosol. In a further feature of this aspect of the invention, the interior of the holding chamber has anti-electrostatic properties to reduce the amount of medicament adhering to the walls of the holding chamber and thereby increase the delivery efficiency of the system. 
         [0005]    In a further aspect of the present invention, a holding chamber is provided with a receptacle member adapted to accept a source of aerosol medicament. The receptacle member may aid in the efficient delivery of medicament to the subject, for example by being vented to allow outside air to be mixed with the medicament aerosol in the holding chamber. In addition, if a rotation is imparted to the outside air brought into the holding chamber, the adhesion of medicament to the walls of the holding chamber can be reduced and the effort necessary to inhale through an apparatus of this type may be reduced. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0006]      FIG. 1  is an assembled view of an example of the aerosol medicament delivery apparatus of the present invention. 
           [0007]      FIG. 2  is a perspective exploded view of the apparatus. 
           [0008]      FIG. 3  is a side view of the delivery member used in the apparatus. 
           [0009]      FIG. 4  is a bottom perspective view of the delivery member. 
           [0010]      FIGS. 5   a  and  5   b  are top and bottom views of the valve element used in the apparatus. 
           [0011]      FIG. 6  is a top perspective view of the delivery member. 
           [0012]      FIG. 7  is a sectional side view of the adaptor member used in the apparatus. 
           [0013]      FIG. 8  is a top perspective view of the adaptor member. 
           [0014]      FIGS. 9   a  and  9   b  are top and bottom views of the receptacle member used in the apparatus. 
       
    
    
     DETAILED DESCRIPTION 
       [0015]    Referring to  FIGS. 1 and 2 , the aerosol medicament delivery apparatus  10  of the present invention is composed of a holding chamber  200  with first and second ends. At the first end of the holding chamber is a receptacle  300  for connection to a source of aerosol medication. For the purposes of the present invention, aerosol medicament or aerosol medication is intended to include finely divided solid or liquid materials that are carried by a gas for delivery to a subject&#39;s respiratory tract, especially to the lungs. This includes nebulized materials. The medicament and carrier gas aerosol composition can be prepared prior to use if it exhibits sufficient physical and chemical stability, or it can be prepared in situ from sources of solid or liquid medicament materials (either in pure form or combined with a suitable solid or liquid solvent, excipient or diluent) and pressurized gas. 
         [0016]    At the second end is a mouthpiece member  100  for delivering aerosol medicament to a subject through a valve  150 . The mouthpiece member includes a housing  101  that defines a passage  102  through which aerosol medicament can be supplied to a subject and has an opening  103  that opens to the outside of the housing. The valve, discussed below, is of one-piece construction. During inhalation the valve permits the flow of aerosol medicament from the holding chamber to the subject, while blocking the inflow of outside air to the passage  102  through the sidewall of the housing of the mouthpiece member. During exhalation, the valve blocks the flow of exhaled air upstream in the direction of the holding chamber, and permits the exhaled air to be exhausted through the sidewall of the housing. 
         [0017]    In an exemplary embodiment, the housing  101  is composed of a delivery member  110  and an adaptor member  170 . The opening  103  may be defined, as it is in part in the exemplary embodiment, by a notch  186  in the adaptor member. The delivery member and adaptor member may be releasably connected by a quick release mechanism  182 . In the exemplary embodiment, the quick release mechanism is a flexible wall, upon which a positioning element  175  may be located. Also, in the exemplary embodiment, the housing is transparent. This has the advantage that it allows for the subject to visually verify the operation of the valve, to ensure opening and closing during treatment. 
         [0018]    Referring to  FIG. 3 , the delivery member  110  may include a subject side section  120 , a connecting ring  130 , and an adaptor side section  140 . In the exemplary embodiment, the subject side section of the delivery member of the mouthpiece is sized and shaped to fit a human mouth, e.g. having an oval shape. The subject end section is defined by a housing composed of a sidewall having a height  124 , and upon which may be provided at least one ridge  125 . Positioning pins  141  may be provided on the adaptor side section of the delivery member. 
         [0019]    Referring to  FIG. 4 , the adaptor side section  140  of the delivery member  110  in this exemplary embodiment has walls  142  arranged around an opening  145 . One or more openings, for example the illustrated notches  147 , is formed in the wall  142  and can define an exhaust opening from the delivery member for exhaled air. This opening is closed by the valve during inhalation, and the opening may be provided with an element to assist in seating a valve member, for example protrusion  146 . The end face  144  of the wall can be used as a surface for holding the valve in place when the apparatus is assembled, in cooperation with an opposed surface on the adaptor member. Also, in this embodiment, the four positioning pins  141  extend from the end face of the wall  142 . 
         [0020]    Referring to  FIGS. 5   a  and  5   b , the one-piece two-way valve system  150  allows for inhalation and exhalation with a single valve. The valve has a base  151 , a first valve element  152 , which has a duck-bill shape in this embodiment, and a second valve element  153 , which is shaped like a hinged flap  153  in this embodiment. In the exemplary embodiment, the valve is composed of a flexible material and there are two hinged flaps  153 . The two valve elements may be joined at or carried on a common base  151 . The base has a thickness  154  that is less than the height of the positioning pins of the mouthpiece, so that the pins may pass therethrough. There is an opening  155  in the base, which may be defined as the perimeter of contact between the duck-bill and the base. The exemplary embodiment has four positioning holes  156  placed near the perimeter of the base, each being sized to admit the matching positioning pins. Thus, when the apparatus is assembled, the positioning pins of the mouthpiece penetrate the positioning holes of the valve base and the valve base forms a substantially airtight seal between the delivery member and the adaptor member. 
         [0021]    The duck-bill is a shape predominantly that of a wedge with a very narrow split across the apex of the wedge. The split is narrow enough that the two edges forming the ends of the duck-bill are substantially in contact when there is no external pressure on the duck-bill. The duck-bill has a span, a height, and a thickness. The height of the duck-bill is the vertical distance between the apex of the wedge where the split is located and the base. The span is the distance of the split across the thin edge of the wedge and the height. The span is sufficiently narrow that the apex of the duck bill will fit within the delivery member without contacting it. Thus, the dead zone within the delivery member is minimized by the valve extending therein. The valve may be as wide as possible to provide for easier inhalation, but just narrower than the passage so that the duck-bill sides do not receive pressure and the lips of the duck-bill are not parted except by inhalation. 
         [0022]    Dead space refers to the volume of the apparatus containing air which is rebreathed. Dead space is inherent in any valve-based system enclosed within a mouthpiece or mask; it is the space between the mouth of a subject and the valve. Any subject has a limited volume of air that may be inhaled, and which then is exhaled. This is the subject&#39;s tidal volume. The inhalation air will contain both oxygen and medicament. The exhalation air will contain carbon dioxide. In a sealed system, all inhalation air will come through the valve and will contain a preferable mixture of medicament laden air. However, this inhalation air will be combined with whatever gases remain sealed within the dead space on their way to being actually inhaled into the subject&#39;s respiratory tract. Similarly, when the subject exhales, all air must pass through this dead zone on the way out the exhaust portion of the valve system. 
         [0023]    Because the subject will be incapable of forcing a complete vacuum within this sealed system, the dead space will contain gases that then will be re-inhaled during the next breathing cycle. Given that the volume of the subject&#39;s lungs is fixed, the larger the volume of the system&#39;s dead space, the smaller the volume of medicament laden air the subject will receive with each breathing cycle. Thus, the larger the volume of dead space, the less efficient the system because increasing dead space causes a buildup of carbon dioxide and rebreathing. Rebreathing carbon dioxide can have an adverse effect on breathing rates and patterns, especially for small children who have very small tidal volumes. Duck-bill valves are more efficient than diaphragm valves because the volume encompassed by the duck-bill is subtracted from space that otherwise would be dead space in a diaphragm-based system. 
         [0024]    The duck-bill is thin enough that the sides of the wedge will flex when the atmospheric pressure on the opposite side of the base from the duck-bill is greater than that above the duck-bill. This causes the edges of the duck-bill to part, letting air flow through the duck-bill in the direction from the base to mouthpiece. Thus, in the present embodiment, air is permitted to flow through the mouthpiece to a subject during inhalation. The duck-bill closes automatically at the end of inhalation when the atmospheric pressure differential is removed, Thus, the flow of exhaled air upstream of the valve to the holding chamber is prevented during exhalation. 
         [0025]    The exemplary embodiment of the present invention provides two hinged flaps  153  extending from on or near the perimeter of the base. Each hinged flap  153  is sized so as to be able to cover a corresponding notch  147  when assembled. Each flap is placed on the base at such a position and at such an angle that when the base is placed onto the positioning pins of the mouthpiece, the flap covers one of the notches  147 . The flap is hinged onto the base so that it may cover the notch  147  during inhalation, thereby preventing the flow of outside air into the interior of the housing through the opening in the sidewall of the housing. When the mouthpiece of the apparatus of the exemplary embodiment is assembled, the notch of the delivery member  147  and the aforementioned notch of the adaptor member  186  may be aligned radially, and the hinged outgas flap  153  is disposed between these notches. The flexible material forming each of the outgas flaps is sufficiently thin to allow an outgas flap to flex through at least a few degrees of flexibility when differences in relative atmospheric pressure caused by human breathing exert flexing pressure on said flap, thereby moving the flap away from the notch  147  during exhalation and allowing exhaled air to pass out of the mouthpiece through the notch  186 . 
         [0026]    Referring to  FIG. 6 , the subject side section  120  of the delivery member may be formed by a sidewall  128  that is generally cylindrical in shape with an oval cross section. The exemplary embodiment has two side points  122 , opposite each other on the sidewall, and two lip points  123 , opposite each other on the sidewall. Each lip point is equidistant between the two side points. There is a contact end  126  where the sidewall is joined to the connecting ring and a lip end  127  opposite the contact end. The upper opening of the sidewall  121  at the lip end is oval. There is a lower opening of the sidewall at the contact end, through which the tip of the duck-bill valve passes. 
         [0027]    Ridges  125  may be provided for placement of the subject&#39;s lips, or to aid in the placement of an adaptor mask on the outside of the delivery member. Shaped correctly, a ridge  125  may be used to seal and mount such a mask with a tight pressure fit. These ridges are placed approximately halfway down the upper section, and are wedge shaped in the exemplary embodiment. Specifically, they are formed by the upper and lower thickness measurements being equal at the side points and the lower thickness being greater than the upper thickness at the lip points. 
         [0028]    Referring to  FIGS. 4 and 6 , the connecting ring  130  between the adaptor side and subject side sections of the delivery member has an interior opening  135 , which may be equal in size to and substantially continuous with the opening of the sidewall of the subject side section. It has an exterior limit  131  that is greater than the interior opening, and a surface  132  where the connecting ring is joined to the subject side section. The surface  132  extends from the sidewall  128  outwards toward the exterior limit  131  where it joins with an exterior wall  133 . 
         [0029]    The exterior wall  133  may be substantially parallel to the sidewall  128  and extends from the top surface in a direction away from the lip end of the subject side section. The exterior wall has an interior surface and an exterior surface, the interior surface being closer to the interior opening of the connecting ring. In the exemplary embodiment, there are two contact openings  134  in the top surface, which are disposed approximately equidistantly around the circumference of the top surface. Each contact hole is adapted to accept a portion of the adaptor member, to help hold the two members of the mouthpiece securely together. On the interior surface of the exterior wall, there may be provided two engaging members  136 , or catches, each being below a contact hole. They are wedge shaped and oriented with the thin end of the wedge towards the adaptor side for ease in connecting and resistance to disconnecting. In the exemplary embodiment, each has a width less than that of the corresponding contact opening above the catch, a length less than that of the distance between the top and bottom of the exterior wall of the connecting ring, and a height less than the length. 
         [0030]    Referring back to  FIGS. 3 and 4 , the width  143  of each section that makes up the wall  142  is approximately as wide as a contact opening in the top surface of the connecting ring. Each wall section is disposed along the interior opening substantially adjacent to a contact opening, thus providing a limit to the flexing of the walls of the adaptor member, which is discussed below. In the exemplary embodiment, each wall section has two positioning pins  141  placed along the end face of the wall, extending in the same direction. They are placed near the edge of the wall sections, and can be placed as far apart from each other as the width of a contact opening in the surface of the connecting ring. Due to their height, the sections of the wall  142  extend into the space of the adaptor member when the apparatus is assembled. Protrusions  146  may be disposed on the perimeter of the opening forming the passage for exhalation air flow (notches  147 ). These protrusions act as stop elements for the exhaust flap portions of the one-piece valve, limiting their travel in an inward direction. As will be seen in more detail below, when the subject inhales, these exhaust flaps are pressed by suction against the stop elements and form a seal so that the pressure of inhalation is fully directed towards drawing the medicament laden air from the holding chamber. 
         [0031]    Referring to  FIG. 7 , the adaptor member  170  may be generally frustoconical in shape, thereby providing for the smooth change in diameter from the holding chamber to the delivery member. In the exemplary embodiment, it is both frustoconical and transparent. A transparent embodiment of the present invention has the additional advantage of allowing the subject to visually verify the presence of the medicament during delivery to the patient. The adaptor member may have a base end  171 , a conical midsection  172 , four wall sections, and a delivery side end  173 . The base end is adapted to cooperate with the edge of the holding chamber, for example forming an exterior wall extending from the end of the cone. The base end of the adaptor member also may have an inner wall  174  extending from the end of the cone. In the exemplary embodiment, each of these two walls having a height of at least 0.5 mm to define a groove for accepting the edge of the holding chamber. In this case, the walls are shaped and positioned such that, when the chamber is positioned between the inner and outer walls and a thin layer of adhesive is applied between the walls, a substantially airtight seal may be formed between the holder and the chamber. Other systems for joining the adaptor member and holding chamber may be used, including permanent bonding or releasable connections. The releasable connection may not be needed when the delivery member is made of two readily-separated components that allow for easy cleaning and for replacement of the valve when necessary, as in the illustrated embodiment. 
         [0032]    Referring to  FIGS. 7 and 8 , the wall arising from the frustoconical midsection  172  of the adaptor member  170  may be divided into four sections, including two catch walls  176  and two vent walls  177  in the exemplary embodiment. These may be placed alternately around the delivery side end of the adaptor member. Each catch wall  176  may have a catch opening  178  sized to admit one of the catches  136  of the connecting ring  130  of the delivery member  110 . A catch wall  176  is positioned on the adaptor member such that its opening  178  is adapted to fit a catch  136  when the two adaptor and delivery members are joined. The end  179  of the catch wall  176  may fit a contact opening  134  of the connecting ring  130  of the delivery member  110 . The catch walls  176  may be flexible, so that they may be bent by the subject applying pressure at the positioning points  175  to release the catch  136  from the opening  178 . This allows the two members of the exemplary housing  101  to be joined and separated in a quick-release fashion. Each valve wall  177  in the exemplary embodiment is U shaped. That is, it is a wall on the long side of the oval opening with a notch  186  in it. Other systems for connecting the adaptor member and delivery member can be used. In addition, the catch and opening could be reversed, i.e. the opening provided on the connecting ring and the catch provided on wall section of the adaptor member. 
         [0033]    The delivery side end of the conical adaptor member may have an opening  185  of substantially the same size as the opening  155 . An airtight seal may be formed between the opposing surfaces of the adaptor member and the delivery member by the valve. That is, the valve base  151  may have opposing surfaces arranged to meet those of the adaptor member and the delivery member and form an airtight seal when the apparatus is assembled. The exemplary embodiment&#39;s adaptor member  170  has a rim  180  around the opening  185  with four positioning openings  181  in the rim, one for each pin  141 . Thus, when the two members are joined, the four pins of the delivery member drop into these openings in the exemplary embodiment. 
         [0034]    Referring to back  FIGS. 1 ,  2  and  7 , the cylindrical holding chamber  200  may be defined by a length of cylindrical tube that extends between the mouthpiece  100  and a source of aerosol medicament and includes the receptacle  300  accepting an outlet from a source of aerosol medicament such as a metered dose inhaler or the like. The tube wall  201  may be sized to fit between the inner wall  174  and the outer wall  171  of the base of the mouthpiece. In the exemplary embodiment, the holding chamber is made of a lightweight metal or alloy, such as aluminum or an alloy thereof. 
         [0035]    The use of such material reduces the risk of resistance to medicament flow by static attraction between the particles of medicament and the holding chamber wall. Alternatively, the surface of a holding chamber of any material may be treated with an anti-electrostatic coating or process to achieve this advantage. In the exemplary embodiment using a metal tube, the tube is anodized which provides the advantage of sealing the micro-porosity of such a tube&#39;s surface and stabilizing it against oxidation. 
         [0036]    Referring to  FIGS. 9   a  and  9   b , the receptacle  300  may include a base with a lip  310 , an opening  350  for accepting a source of aerosol medicament in the base with a collar  370  extending into the chamber  200 , an air vent  320 , and a supporting wall  340  that surrounds the opening arising from the base into the chamber. The exemplary embodiment has four vents. The receptacle base is sized to fit within the tube of the holding chamber. It may be formed of a resilient and flexible material such that it may be removed from the chamber tube (e.g., for cleaning) and replaced any times without loss of functionality, such as maintenance of structural integrity or the ability of the receptacle to form a substantially airtight seal with the tube, throughout the life of the apparatus. In the exemplary embodiment, the receptacle may be removed and replaced hundreds of times without ripping, tearing or otherwise harming the functionality of the apparatus. This removal resilience also applies to the removal and replacement of the source of aerosol medicament from the apparatus. The lip  310  of the receptacle fits around the perimeter of the base of the member so that the lip extends beyond the edge of the tube. The lip may be sized such that it forms a substantially airtight seal with the tube. Other systems can be used to join the receptacle to the tube if desired. 
         [0037]    The opening  350  of the receptacle of the exemplary embodiment may be sized to accept several different types of aerosol medicament sources such as MDIs. The collar  370  is sufficiently long and flexible to form a seal with the aerosol medicament source when one is admitted into the receptacle. The supporting wail  340  of the exemplary embodiment is provided with cyclone baffles  330  placed upon the outside of the wall (relative to the opening) and support ribs  360  radially placed upon the inside of the wall. The support ribs  360  extend from the wall towards the collar  370 . They are sized so that there is space for the collar to be pressed up against the ribs when a typical MDI is inserted into the opening. Thus, an airtight seal may be formed around the source of the aerosol medicament. The support ribs of the exemplary embodiment provide support to the source of aerosol medicament by holding that source against the structure of the collar. 
         [0038]    The vents  320  allow outside air to be drawn into the holding chamber during inhalation. This helps to push the aerosol medicament to the subject during inhalation. Each cyclone baffle  330  extends towards the base and is aligned with a vent  320  so that the point where the baffle reaches the base is just beyond the vent. The baffle thus covers the vent. The baffle may have a width sufficient to form a seal between the supporting wall and the tube wall of the chamber. By using the baffle to direct airflow coming through the vents, a rotational flow is imparted to the air entering the chamber through the vents. In the exemplary embodiment, the placement of the cyclone baffles above the vents and next to the wall of the holding chamber wall directs outside air to and along the wall of the holding chamber. This reduces the tendency for medicament to adhere to the wall of the holding chamber. Although each of the four vents have been provided with a cyclone baffle in the present embodiment, this may not be necessary in all cases. 
         [0039]    The exemplary embodiment of the present invention is steam autoclavable either assembled or disassembled. This advantage arises from both the choice of materials used, as herein discussed, and the materials and methods of assembling the components of the invention, such as the quick release mechanism  182  and the use of high-temperature adhesive at the junction of adaptor member  170  and holding chamber  200 . Further, the present invention is easily disassembled for cleaning and parts replacement by a non-technical person. 
         [0040]    While a detailed description of the present invention has been provided above, the invention is not limited thereto. Modifications that do not depart from the scope and spirit of the invention will be apparent to those skilled in the art. The invention is defined by the claims that follow.