Abstract:
A miniaturized pre-filled, single-use, disposable, small volume medication nebulizer unit for medicinal use that delivers a mist of properly sized aerosol particles of medicament to the patient with a very high level of efficiency. The nebulizer can be effectively used in conjunction with conventional tee and mouthpiece patient interface devices as well as with more sophisticated interface devices such as dosimetric/reservoir systems, or mechanical ventilator systems.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This is a Continuation-In-Part of U.S. Ser. No. 11/894,860 filed Aug. 21, 2007. 
     
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
       [0002]    Not Applicable 
       INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT DISC 
       [0003]    Not Applicable 
       BACKGROUND OF THE INVENTION 
     Field of the Invention 
       [0004]    The present invention relates generally to inhalation devices. More particularly, the invention concerns a miniaturized pre-filled, single-use, disposable, small volume nebulizer for medicinal use that delivers a mist of properly sized aerosol particles of medicament to the patient with a very high-level of efficiency. 
       DESCRIPTION OF RELATED ART INCLUDING INFORMATION DISCLOSED UNDER 37 CFR 1.97 AND 1.98 
       [0005]    In medicine, a nebulizer is defined as a device that is used to administer medication to the patient&#39;s airways in the form of a liquid mist, more properly known as an aerosol. In general the prior art devices used for producing medical aerosols fall into two categories; the small volume nebulizer (SVN), and the metered dose inhaler (MDI). The small volume nebulizer (SVN) has traditionally been the apparatus of choice for delivery of therapeutic aerosols. The delivery apparatus typically consists of a multi-use disposable or reusable nebulizer, a mouthpiece or facemask, and a pressurized gas source usually oxygen or air. The metered dose inhaler (MDI), on the other hand, typically contains the active drug, dissolved in chlorofluorcarbon (CFC) or chlorofluroalkane (CFA) propellants and excipients plus a metering valve. The drug-containing canister of the device is generally fitted to a mouthpiece actuator and spacer or valved holding chamber, and activation of the device by compressing it results in the release of a metered dose of medication. 
         [0006]    Various types of prior art inhalers have also been offered for sale and are in wide use. Inhalers have the advantage of portability but have been criticized on the basis that patients often lack the coordination and psychomotor skills to use them properly without professional supervision. This dichotomy of available device types (nebulizers vs. inhalers) has lead to a great deal of controversy regarding which method is superior, although many experts have concluded that nebulizers and inhalers are essentially equivalent in terms of therapeutic outcomes. Accordingly, in many respects, the choice of device revolves around non-outcome related factors such as cost, convenience, ease-of-use, safety, patient preference, patient compliance and adherence, as well as the availability of medications in one or both delivery forms. Despite alternative methodologies, it is clear that inhaled medication delivery by nebulizer is a permanent part of the treatment options for respiratory disease patients and is becoming a useful tool for systemic drug delivery as well. 
         [0007]    This being the case, there is an abundance of plastic disposable medication nebulizers on the market, but the vast majority of these devices are essentially clones, differing from one another mainly in appearance. Functionally, they are essentially identical. The overriding similarity between all these devices is that they are all supplied empty and the medication they are to nebulize must be transferred into them prior to commencement of the treatment by either the professional respiratory therapist in the hospital setting or the patient or patient&#39;s caregiver in the home setting. 
         [0008]    Recently, various investigators and companies have sought to improve liquid nebulization. However, due to the physics of jet nebulization, the possibility of performance improvements in the jet nebulizer itself are very limited. Many of the improvements have involved electronic controlled or driven nebulizers that have improved efficiency but are also so expensive as to be out-of-reach for the typical routine nebulization purposes. 
         [0009]    As will be discussed more fully hereinafter, there are various well recognized technical limitations to nebulizer use. These include the following: 
         [0000]    1. Excessive patient dosing time.
 
2. Dose of drug delivered to the patient is undesirably affected by patient breathing parameters that may result in unacceptable variations in drug delivery dose.
 
3. Cleaning of the nebulizer after each use is time-consuming and frequently neglected thereby providing a possible avenue for nosocomial infection (bacteria/viral spread within a healthcare organization).
 
4. In a hospital environment, excessive amounts of technologist time is required for each patient treatment.
 
5. Release of the drug to atmosphere is not only wasteful but can be detrimental to healthcare workers who breathe “second-hand” aerosol drugs.
 
6. Because of lengthy treatment times, patients may become fatigued and compliance is compromised.
 
7. Hospital use is often determined by price only, not performance.
 
         [0010]    In light of the aforementioned drawbacks, Dr. J. H. Dennis, a highly recognized aerosol researcher, has stated as follows in the Practical Handbook of Nebulizer Therapy. London, Martin Dunitz; 2004: 42-43:
       “It is clear that neither pressurized metered dose MDI&#39;s, nor DPI&#39;s meet all the necessary requirements despite the enormous amounts of pharmaceutical funding which has been devoted to improvement of these devices over the past three decades.”       
 
         [0012]    It is this problem that the present invention seeks to address by providing the novel miniaturized pre-filled, single-use, disposable, small volume medication nebulizer unit of the invention. 
       BRIEF SUMMARY OF THE INVENTION 
       [0013]    It is an object of the present invention to provide a novel miniaturized pre-filled, single-use, disposable, small volume medication nebulizer unit for medicinal use that delivers a mist of properly sized aerosol particles of medicament to the patient with a very high-level of efficiency. 
         [0014]    Another object of the invention is to provide a nebulizer of the aforementioned character that comprises a unique means for packaging an inhalation drug in a preferred unit-dose, single-use disposable container that confers the benefits of unit-dose packaging while it simultaneously performs the function of highly effective drug aerosolization. 
         [0015]    Another object of the invention is to provide a nebulizer of the character described that is small in physical size for convenience of packaging, storage, dispensing and operation. 
         [0016]    Another object of the invention is to provide a miniaturized, pre-filled, single-use, disposable, nebulizer that can be produced in large quantities at minimal cost by conventional thermoplastic injection molding means. 
         [0017]    Another object of the invention is to provide a miniaturized nebulizer as described in the preceding paragraphs that can be effectively used in conjunction with conventional tee and mouthpiece patient interface devices as well as with more sophisticated patient interface devices such as dosimetric/reservoir systems, or mechanical ventilator systems. 
         [0018]    Another object of the invention is to provide a miniaturized, pre-filled, single-use, disposable nebulizer that effectively mitigates against the possibility of self-contamination or cross-contamination due to improper cleaning of the device. 
         [0019]    Another object of the invention is to provide a miniaturized nebulizer of the class described that effectively minimizes practitioner set-up and preparation time thereby conferring significant labor savings benefits upon healthcare organizations that employ such practitioners for the purpose of administering medicated aerosol therapy. 
         [0020]    Another object of the invention is to provide a miniaturized, pre-filled, single-use, disposable nebulizer that effectively reduces or eliminates practitioner clean-up time following administration of the contained medication thereby conferring significant labor savings benefits upon healthcare organizations that employ such practitioners for the purpose of administering medicated aerosol therapy. 
         [0021]    Another object of the invention is to provide a nebulizer of the type described in the preceding paragraphs that incorporates a miniature nebulizer attached to a dosimetric reservoir configuration that delivers superior patient dose consistency and repeatability even over a wide range of patient breathing parameters. This feature uniquely provides the ability to accurately predict the actual dose delivered to the patient. Such calculations may be made to within ±20% of that predicted when using the dose quantification equation discussed hereinafter. 
         [0022]    Another object of the invention is to provide a miniaturized, pre-filled, single-use, disposable, nebulizer unit that, when combined with an appropriate dosimetric reservoir system, provides a substantial reduction of drug release to the ambient atmosphere thereby protecting caregivers and other personnel by reducing or minimizing exposure to “second-hand” aerosol drugs. 
         [0023]    It is an object of the present invention to provide an inhalation apparatus which will deliver an aerosolized medication to the patient which comprises up to 70% of the medication aerosolized. 
         [0024]    Another object of the invention is to provide the best features of both breath-enhancement and dosimetric/reservoir technology. 
         [0025]    Yet another object of the apparatus is to provide for patient drug dose delivery rates of up to 5 times faster than that of typical nebulizer/tee configurations. 
         [0026]    Another object of the invention is to provide delivered dose consistency even over a wide range of patient breathing parameters. 
         [0027]    Another object of the invention is to provide an apparatus which will deliver to the patient essentially the same particle size distribution of the aerosol mist that originates from the nebulizer itself. 
         [0028]    Yet another object of the invention is to provide means for safely filtering air exhaled from the patient before its release to room atmosphere. 
     
    
     
       BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS 
         [0029]      FIG. 1  is a generally perspective view of one form of the single dose disposable nebulizer unit of the invention with both closures in place as if filled with medication. 
           [0030]      FIG. 2  is an enlarged, cross-sectional view taken along lines  2 - 2  of  FIG. 1 . 
           [0031]      FIG. 3  is an exploded, generally perspective, cross-sectional view of the nebulizer unit illustrated in  FIG. 2  of the drawings. 
           [0032]      FIG. 4  is a generally perspective view illustrating the nebulizer unit of the invention interconnected with a patient delivery device. 
           [0033]      FIG. 5  is a greatly enlarged, cross-sectional view taken along lines  5 - 5  of  FIG. 4 . 
           [0034]      FIG. 6  is a view taken along lines  6 - 6  of  FIG. 5 . 
           [0035]      FIG. 7  is a cross-sectional view taken along lines  7 - 7  of  FIG. 5 . 
           [0036]      FIG. 8  is an enlarged, cross-sectional view taken along lines  8 - 8  of  FIG. 5 . 
           [0037]      FIG. 9  is an enlarged cross-sectional view taken along lines  9 - 9  of  FIG. 5 . 
           [0038]      FIG. 10  is a cross-sectional view taken along lines  10 - 10  of  FIG. 5 . 
           [0039]      FIG. 11  is a fragmentary cross-sectional view of the upper portion of the nebulizer unit better illustrating the construction of the nebulizer assembly. 
           [0040]      FIG. 12  is a generally perspective view, partly in cross section, showing one form of the nebulizer unit of the invention interconnected with a conventional mouthpiece, tee and aerosol flex tube reservoir. 
           [0041]      FIG. 13  is an enlarged, cross-sectional view taken along lines  13 - 13  of  FIG. 12 . 
           [0042]      FIG. 14  is a cross-sectional view taken along lines  14 - 14  of  FIG. 13 . 
           [0043]      FIG. 15  is a cross-sectional view taken along lines  15 - 15  of  FIG. 14 . 
           [0044]      FIG. 16  is a generally perspective view of an alternate form of the single dose disposable nebulizer unit of the present invention. 
           [0045]      FIG. 17  is an exploded, generally perspective view of the nebulizer unit illustrated in  FIG. 16  of the drawings. 
           [0046]      FIG. 18  is an enlarged, generally perspective view of one form of the airflow baffle component of this latest form of the invention. 
           [0047]      FIG. 19  is a cross-sectional view taken along lines  19 - 19  of  FIG. 16 . 
           [0048]      FIG. 20  is a greatly enlarged, cross-sectional view taken along lines  20 - 20  of  FIG. 19 . 
           [0049]      FIG. 21  is a greatly enlarged, cross-sectional view taken along lines  21 - 21  of  FIG. 19 . 
           [0050]      FIG. 22  is a greatly enlarged, generally perspective fragmentary view of the upper right hand portion of  FIG. 23 . 
           [0051]      FIG. 23  is a generally perspective view of still another form of the single dose disposable nebulizer unit of the present invention. 
           [0052]      FIG. 24  is a partly broken away, generally perspective view of one form of the check valve diaphragm of the invention illustrated in  FIG. 23 . 
           [0053]      FIG. 25  is a side elevation will view of the check valve diaphragm of the invention illustrated in  FIG. 23   
           [0054]      FIG. 26  is a cross-sectional view taken along lines  26 - 26  of  FIG. 23 . 
           [0055]      FIG. 27  is an enlarged cross-sectional view taken along lines  27 - 27  of  FIG. 26 . 
           [0056]      FIG. 28  is an enlarged view taken along lines  28 - 28  of  FIG. 23 . 
           [0057]      FIG. 29  is an enlarged cross-sectional view taken along lines  29 - 29  of  FIG. 23 . 
           [0058]      FIG. 30  is a greatly enlarged cross-sectional view illustrating the operation of the check valve of the apparatus of this latest form of the invention that controls fluid flow through the exit path from the third chamber of the device. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0059]    Referring to the drawings and particularly to  FIGS. 1 through 3 , one form of the miniaturized jet nebulizer unit of the invention for delivering a multiplicity of particles of aerosolized medication of a selected size to a patient is there illustrated and generally designated by the  14 . As will be discussed more fully hereinafter, a novel feature of the nebulizer unit of the invention resides in the fact that it can be supplied pre-filled with the required inhalable liquid medication, used for a single treatment, and then discarded. 
         [0060]    As previously mentioned, nebulizer  14  is quite small and preferably, but not limitedly, has an overall length “L” of between about 2.0 and about 3.0 inches ( FIG. 2 ). Uniquely, nebulizer  14  serves as both the single dose package for the medication to be delivered to the patient and in a manner presently to be described, as a means for converting the liquid medication to a respirable aerosol. In practice, the nebulizer unit  14  can be produced from a commercial polymer in very high quantities by multi-cavity thermoplastic injection molding techniques of a character well understood by those skilled in the art. The number of components that make up the nebulizer unit is intentionally minimized to facilitate molding and to enable automatic robotic assembly and testing. Inasmuch as the nebulizer unit is discarded after each treatment, its use negates the need for extensive preparation and filling prior to the treatment by healthcare professionals or home care patients. Further, because it is intended to be discarded after use, there is no need for nebulizer cleaning thereby eliminating this time-consuming step and removing any doubt about the quality and effectiveness of the cleaning process. These novel qualities of the nebulizer unit of the invention serve to significantly reduce the immense amount of professional labor time by hospital respiratory care departments and at the same time substantially reduce the possibility of iatrogenic cross-contamination via improperly cleaned nebulizers. For the pharmaceutical company, the unique design of the nebulizer unit of the invention provides a higher margin of medication safety because the need for having either a healthcare practitioner or a home care patient transfer a drug from its packaged container into the nebulizer unit is eliminated. The deliberate integral capacity limitation of the nebulizer unit for any given drug also mitigates against unauthorized admixture of the self-contained drug with other agents. 
         [0061]    Referring particularly to  FIGS. 1 through 3  of the drawings, the nebulizer unit  14  of the invention here comprises a central body  16  having first open end  16   a , a second end  16   b  and a tapered sidewall  16   c . Tapered sidewall  16   c  defines a fluid reservoir  18  for containing a single dose of between about 2 and about 4 milliliters of aerosolizable liquid medicament “LM”. As indicated in  FIG. 11 , central body  16  has a diameter “DIA” of between about 0.5 and about 0.8 inches. 
         [0062]    Disposed within reservoir  18  for converting the aerosolizable liquid medicament into an aerosolized medication is a nebulizer assembly  20  that includes a moldable plastic nebulizer body  22  having a nebulizer orifice  22   a  and a deflector element  22   b  ( FIGS. 2 and 3 ). Mounted within central body  16  is an elongated fluid flow tube  24  that forms a part of the nebulizer assembly of the present invention and includes a gas inlet port  24   a  and a gas outlet port  28  that is in communication with nebulizer orifice  22   a.    
         [0063]    As best seen by referring to  FIGS. 2 ,  3  and  9 , nebulizer body  22  is telescopically receivable over flow tube  24  and includes a plurality of circumferentially spaced ribs  22   c  that cooperate with the outer wall of the flow tube to define a plurality of fluid flow paths  25  ( FIG. 9 ). When the nebulizer body is in position over the flow tube, the components cooperate to define a transverse fluid passageway  27  that is in communication with the plurality of fluid flow passageways  25  and with gas outlet port  28 . With this construction, when the reservoir  18  is filled with the aerosolizable liquid medicament “LM” and when the fluid flow tube  24  is interconnected with a source of gas under pressure “S” ( FIG. 4 ), the aerosolizable liquid medicament “LM” will, in a manner presently to be described, be aerosolized to produce a multiplicity of particles of aerosolized medication. 
         [0064]    Removably connected to central body  16  is a bottom closure assembly  26  that includes a supporting base  29  and an elongated stem  30  that is connected to supporting base  29  in the manner best seen in  FIG. 3  of the drawings. As indicated in the drawings, elongated stem  30  is telescopically, sealably receivable within the fluid flow tube  24  for sealing the gas inlet port  24   a  thereof. In one form of the present invention, supporting base  29  functions to enable proper positioning of nebulizer  14  for automated robotic filling procedures. In this regard, it should be noted that the overall design of the nebulizer unit of the present invention is such that it is fully compatible with an automated robotic assembly process, with automated robotic post-assembly functional testing and quality assurance inspection, and with automatic robotic packaging processes for packaging and shipping the assembled unit in a fashion that meets the needs of the pharmaceutical companies. 
         [0065]    Removably connected to first open end  16   a  of central body  16  is a top closure assembly  32  that comprises a part of the fill means of the invention for filling reservoir  18  with a suitable liquid medicament. Top closure assembly  32  functions to close the first open end of the central body and also functions to enable the reservoir  18  to be filled with the aerosolizable liquid medicament “LM”. As best seen in  FIG. 3  of the drawings, assembly  32  comprises a closure cap  34  that includes a top wall  34   a  and a tapered skirt portion  34   b  that is connected to the top wall and depends therefrom. Tapered skirt portion  34   b  includes a reduced diameter portion  35  that is sealably receivable within open end  16   a  of central body portion  16  in the manner illustrated in  FIG. 2  of the drawings. This is but one form of closure that was designed into the working prototype to demonstrate proof of concept. Many other forms of closure are contemplated and the unit is intentionally made adaptable to different closure methodologies as will be required by different pharmaceutical companies. 
         [0066]    Top wall  34   a  of the closure  34  is provided with an aperture  37  that sealably receives an elastomeric plug  38 . As indicated in  FIG. 3 , aperture  37  can be traversed by the needle “N” of the automated filling apparatus (not shown) that contains the liquid medicament that is to be used to fill the reservoir  18 . This is but one form of filling that was designed into the working prototype to demonstrate proof of concept. Many other forms of filling are contemplated based upon the variety of automated filling machinery presently available in the pharmaceutical industry. 
         [0067]    After receipt of the requisite number of units by the pharmaceutical company, the units can be filled with a suitable liquid medicament by means of an automated robotic filling process, as previously mentioned, thereby rendering them “pre-filled” in the perspective of the end-user. 
         [0068]    Elongated stem  30  effectively seals elongated fluid tube  24  against leakage of liquid medication through  28  after filling and during any subsequent transport of the packaged pre-filled nebulizers before they are used. Immediately prior to use, bottom closure assembly  26  is manually twisted and removed thereby withdrawing the stem  30  from the fluid tube  24  thus readying the device for use. Bottom closure assembly  26  is now discarded. 
         [0069]    Turning now to  FIG. 5  of the drawings, when the nebulizer unit of the present invention is to be used with a dosimetric patient delivery device “D”, such as that described in U.S. Pat. No. 5,727,542 issued to one of the present inventors, the bottom closure assembly  26  is removed and discarded, then the top closure assembly  32  is removed from the central body portion  16  and an injection molded connector adapter  42  is connected to the central body portion in the manner illustrated in  FIGS. 5 and 10  of the drawings. Connector adapter  42  includes inlet ports  42   a  that are in communication with an expansion chamber  42   b  for expanding the plume of driving gas and decelerating the multiplicity of particles of aerosolized medication emitted from the nebulizer orifice  22   a.    
         [0070]    As best seen in  FIGS. 5 ,  7  and  10  of the drawings, connector adapter  42  further includes an internal baffle assembly  44  for reducing the size of the multiplicity of particles of aerosolized medication reaching the patient delivery device. In this regard, the volume of expansion chamber  42   b  must be sufficiently large to enable the aerosol-laden gas plume emitting from the nebulizer orifice  22   a  to sufficiently re-expand and for the multitude of aerosol particles produced to decelerate in order that the larger particles deliberately encounter the baffling effects of the device and recombine into liquid droplets which are recycled through the nebulizer while the smaller, respirable, particles are effectively emitted from the nebulizer and carried forward to the patient by the gas flow through the nebulizer. 
         [0071]    While in the preferred embodiment of the invention, the expansion, or deceleration, chamber  42   b  is provided as a separate component that can be conveniently attached to the selected patient delivery interface in series with the nebulizer unit, and the deceleration chamber can, for particular end use requirements, be incorporated into the basic nebulizer unit. 
         [0072]    The dosimetric patient delivery device “D”, such as that described in U.S. Pat. No. 5,727,542, when coupled with the nebulizer  14  in a manner illustrated in  FIGS. 4 ,  5  and  10  of the drawings, provides the ability to semi-quantitize the patient dose and deliver a drug with such efficiency that often the patient inhalation time to receive a required dose of medication can be reduced to a fraction of that now required using prior art inhalation devices. This novel combination delivers superior patient dose consistency and repeatability even over a wide range of patient breathing parameters. It also provides the ability to accurately predict the actual dose delivered to the patient within ±20% of that predicted when using the dose quantification equation presently to be discussed. Because of its pertinence, U.S. Pat. No. 5,727,542 is hereby incorporated by reference as though fully set forth herein. 
         [0073]    Operationally, the device described and incorporated by reference Patent &#39;542 includes a novel, almost resistance-free flapper valve mechanism which directs the output of nebulizer  14  to the patient upon inhalation, and into a reservoir bag “RB” during the period of patient exhalation ( FIG. 4 ). That aerosol which is temporarily retained in the bag becomes additional medication for the patient upon the next inhalation and supplements the delivery of medication provided by real-time operation of the nebulizer rather than being shunted out through the expiratory pathway. Typically in conventional, prior art nebulizer devices, the medication aerosolized during the patient&#39;s expiratory phase is lost to the atmosphere and essentially wasted. The immediate obvious benefits of the system of the present invention as illustrated in  FIGS. 4 ,  5  and  10  of the drawings are: (1) drug delivery efficiency is increased dramatically (on average by a factor of 2.4 times); (2) far less medication is wasted by release to the atmosphere; (3) if oxygen is used as the driving gas to power the nebulizer, the fraction of inspired oxygen (FIO 2 ) provided to the patient will be maintained at a high level. 
         [0074]    A less-obvious secondary benefit of the invention resides in the more consistent and reproducible dosing quantities to the patient. If the actuating flow of oxygen or air to the nebulizer unit is in the region of 6 or 7 liters per minute (L/min), and if the patient&#39;s minute ventilation (tidal volume multiplied by respiratory rate) is essentially the same as the actuating flow, use of the system of the present invention minimizes very greatly, changes in drug delivery due to differing breathing patterns. Inasmuch as these operating parameters closely match typical human breathing patterns, this system will accommodate a range of patients from pediatrics through adults. In this regard, experience has shown that the system, when used with adult or semi-adult patients, will maintain dose repeatability to within ±20%. 
         [0075]    Further, from the Dose Quantification equation presently to be discussed, it is obvious that the patient delivered dose of medication is directly proportional to the drug concentration (mg/mL) being aerosolized and the treatment time, all other factors being constant. Therefore, by proper selection of the drug concentration in the pre-filled nebulizer unit, and regulation of the treatment time, the desired doses can be delivered to the patient in as little as one-minute of treatment time. 
         [0076]    In using the apparatus of the invention in connection with a dosimetric patient delivery device “D”, the top closure assembly  32  is disconnected from the body portion  16  and the connector adapter  42  is interconnected with the inlet port of the dosimetric patient delivery device “D” in the manner illustrated in  FIGS. 5 and 10  of the drawings. This done, the bottom closure assembly  26  is removed from the elongated fluid flow tube  24  thereby exposing the gas inlet port  24   a . Next, the fluid flow tube  24  is interconnected with the source of gas under pressure “S” ( FIG. 4 ). The gas is preferably supplied to the nebulizer from the source “S” at a flow rate of about 6 to 7 liters per minute. As illustrated in  FIG. 5 , the gas flowing through the gas inlet port  24   a  in the direction of the arrow  45  passes through the very small nebulizer orifice  28  provided in the nebulizer body  24 . As the gas courses upwardly through the fluid flow tube  24 , it creates a partial vacuum in the circumferentially spaced fluid passageways  25 . This vacuum causes the level of the liquid medicaments in the reservoir  18  to flow into passageways  25  in the direction of the arrow  47  and then to flow over the top of the fluid passageways  25 . Due to the basic design of the nebulizer and in accordance with the Bernoulli effect, when the stream of gas flowing through the fluid flow tube strikes the liquid drawn from the reservoir it will be predictably converted into a fine mist containing a mixture of particles of aerosolized medication of varying sizes that will be carried upwardly through spray orifice  22   a  formed in plastic nebulizer body  22 . In the present form of the invention, the nebulizer orifice produces a multiplicity of particles comprising larger particles of a size exceeding 5 microns and smaller particles of a size between 0.2 to 5 microns. 
         [0077]    After flowing through orifice  22   a , the fine particulate-laden mist following impact with the selector element  22   b  will flow into expansion chamber  42   b  of the connector adapter  42  and around and about baffle  44  in the direction of the arrows  49  in a manner to decelerate the multiplicity of particles of aerosolized medication emitted from the nebulizer orifice  22   a . This deceleration of the particles reduces the size of the particles reaching the outlet port of the device and limits the size of the particles that ultimately reach the patient. 
         [0078]    Through use of the combination nebulizer and dosimetric patient delivery device “D” as described in the preceding paragraphs, the following Dose Quantification equation can be effectively used in predicting the delivered patient dose [Inhaled Mass, predicted (IMp)]: 
         [0000]      IMp= C ×AGR× K ×SE× T    
         [0000]    where: 
         [0079]    IMp: Inhaled Mass, predicted (mg) 
         [0080]    C: Drug Concentration (mg/mL) 
         [0081]    AGR: Aerosol Generation Rate, i.e., the rate of conversion of liquid to aerosol, (mL/min) 
         [0082]    K: AGR Constant; fractional multiplier representing the typical drug content as fraction of AGR 
         [0083]    SE: System Efficiency; fractional multiplier representing the System Efficiency (i.e., percentage of output drug/nebulizer output) 
         [0084]    T: Time of aerosolization, i.e., Treatment Time, (minutes) 
       Example 
       [0085]    Calculate predicted dose to patient when aerosolizing a medication, such as albuterol, with a concentration [C] of 5 mg/mL for one minute with an AGR of 0.25 and a constant [K] of 0.5 and SE of 0.65. 
         [0000]      IMp=5×0.25×0.5×0.65×1=0.32 mg 
         [0086]    An Inhaled Mass (delivery) of 0.32 mg of albuterol is typical of the nominal dose of albuterol delivered by most conventional prior art small volume nebulizers. 
         [0087]    Turning now to  FIGS. 12 ,  13  and  14 , the nebulizer unit of the invention is there shown interconnected with a different form of patient delivery device, here shown as a conventional mouthpiece and tee connector assembly “MPA” that comprises a corrugated aerosol reservoir flex tubing “T” having a length “L” and a conventional mouthpiece “MP”. 
         [0088]    As best seen in  FIG. 14 , assembly “MPA” is provided with a skirt “MPS” having inlet opening “O”. To interconnect the nebulizer unit of the invention with the mouthpiece assembly, the connector adapter  42  is telescopically received over the skirt “MPS” in the manner depicted in  FIG. 14 . 
         [0089]    Following removal of the lower closure assembly  26 , the fluid flow tube  24  is interconnected with the source of gas under pressure “S” ( FIGS. 12 ,  13  and  14 ). As illustrated in  FIG. 14 , the gas flowing through the gas inlet port  24   a  in the direction of the arrow  45  passes through the very small nebulizer orifice  28  provided in the nebulizer body  24 . As before, as the gas courses upwardly through the fluid flow tube  24  it creates a partial vacuum in the circumferentially spaced fluid passageways  25 . This vacuum causes the level of the liquid medicaments in the reservoir  18  to flow into passageways  25  and then to flow over the top of the fluid passageways  25 . Due to the basic design of the nebulizer, when the stream of gas flowing through the fluid flow tube strikes the liquid drawn from the reservoir, it will be predictably converted into a fine mist containing a mixture of particles of aerosolized medication of varying sizes that will be carried upwardly through spray orifice  22   a  formed in plastic nebulizer body  22 . 
         [0090]    After flowing through orifice  22   a , the fine particulate-laden mist following impact with the selector element  22   b  will flow into expansion chamber  42   b  of the connector adapter  42  and around and about baffle  44  in the direction of the arrows  49  in a manner to decelerate the multiplicity of particles of aerosolized medication emitted from the nebulizer orifice  22   a . The particles of aerosolized medication will then flow to the internal chamber “IC” of the mouthpiece, along the length of the mouthpiece, outwardly of the mouthpiece outlet and into the mouth of the patient. 
         [0091]    By way of summary, the several advantages of the apparatus of the present invention for hospitals and home care agencies include the following: 
         [0000]    1. Patient delivery time using the combination nebulizer  14  and dosimetric patient delivery device “D” for the delivery of albuterol and similar inhalable drugs can be reduced to about a one-minute treatment time.
 
2. Influence of patient breathing pattern on drug delivery can be substantially minimized or negated.
 
3. Single-use “throw-away” technology embodied in the apparatus of the invention completely eliminates the need for post-treatment nebulizer cleaning and removes all doubt about the effectiveness of this procedure.
 
4. Within limits, through use of the apparatus of the invention, patient dose is reasonably quantifiable and predictable.
 
5. Total time for hospital patient treatments can be greatly reduced, through reduction of both pre-treatment set-up time and post-treatment clean-up time, thereby resulting in both labor-savings and cost-savings for the facility.
 
6. The use of the apparatus of the invention, in combination with the dosimetric patient delivery device “D,” substantially reduces atmospheric contamination to less than approximately 15% of nebulizer loading dose.
 
7. The very short treatment time of approximately one minute contributes to improved patient compliance, especially with patients receiving multiple inhalation drugs.
 
8. Particle size control can be readily built into the nebulizer design; that is, different particle baffling designs can be made available for different desired particle sizes as characterized by measurements of mass median aerodynamic diameter (MMAD).
 
9. Device acquisition cost to the healthcare facility or home care agency is substantially or completely offset by labor savings in the hospital environment and probable reduction in service or maintenance calls for home care patients undergoing self-treatment in the home environment.
 
         [0092]    Referring to the drawings and particularly to  FIGS. 16 ,  17  and  19 , one alternate form of aerosol inhalation apparatus is there shown and generally designated by the numeral  52 . This form of the invention is similar in some respects to the apparatus illustrated and described in  FIGS. 1 through 11  and like numerals are used in  FIGS. 16 through 22  to identify like components. Apparatus  52  here comprises a sectionalized main housing  54  to which is attached an inflatable bag  56  and nebulizer means, shown here as a nebulizer unit  14  which is substantially identical in construction and operation to that previously described in connection with the embodiment of  FIGS. 1 through 11 . A first end  54   a  of the main housing is provided with a standard size breathing port  62  for ready patient interfacing with the aerosol system via a conduit, or breathing tube  63  ( FIG. 16 ). In a manner presently to be described, the various sections of chambers of the main housing are interconnected by appropriately baffled fluid flow passageways. 
         [0093]    Turning particularly to  FIG. 19 , the nebulizing means, or nebulizer unit  14 , of this latest embodiment comprises a central body  16  having first open end  16   a , a second end  16   b  and a tapered sidewall  16   c . Tapered sidewall  16   c  defines a fluid reservoir  18  for containing a single dose of between about 2 and about 4 milliliters of aerosolizable liquid medicament “LM”. As before, central body  16  has a diameter of between about 0.5 and about 0.8 inches. 
         [0094]    Disposed within reservoir  18  for converting the aerosolizable liquid medicament into an aerosolized medication is a nebulizer assembly  20  that includes a moldable plastic nebulizer body  22  having a nebulizer orifice  22   a  and a deflector element  22   b  ( FIGS. 2 and 3 ). Mounted within central body  16  is an elongated fluid flow tube  24  that forms a part of the nebulizer assembly of the present invention and includes a gas inlet port  24   a  and a gas outlet port  28  that is in communication with nebulizer orifice  22   a . As in the earlier described embodiment of the invention, the nebulizer unit can be supplied pre-filled with the required inhalable liquid medication, used for a single treatment, and then discarded. 
         [0095]    Carried by a wall  68  of housing  54  which is disposed directly above nebulizer  14 , is access means for accessing nebulizer  14  to supply medication fluid to reservoir portion  18  thereof. In the embodiment of the invention shown in  FIG. 19  of the drawings, the accessing means comprises a self-sealing, penetrable septum  70  which, as shown in  FIGS. 17 and 19 , is sealably mounted within an aperture  72  provided in top wall  54  of housing  54 . For certain applications, septum  70  can also comprise a split septum adapted to receive a blunt cannula. Septum  70  is preferably constructed of soft rubber or other suitable elastomer material which is readily penetrable by a blunt cannula or by the needle “N” of a hypodermic syringe ( FIG. 16 ). 
         [0096]    Nebulizer unit  14  also includes a gas inlet means here comprising a gas inlet port  76 , which is interconnected with a source of gas under pressure, such as a tank “T” ( FIG. 17 ). The nebulizer gas inlet means functions to permit the controlled introduction into the nebulizer of a selected gas under pressure in the manner previously described herein, to cause nebulizing of the fluid disposed within reservoir  18  of the nebulizer. The fluid disposed within reservoir  18  can comprise any of a large number of medications, or mixtures thereof, depending upon the end use to be made of the apparatus. 
         [0097]    As best seen in  FIG. 19  of the drawings, housing  54  includes a downwardly extending connector segment  78  which is adapted to receive the upper portion of tapered sidewall  16   c.    
         [0098]    Disposed within a first or intermediate chamber  77  of housing  54 , is the important airflow baffle  80  of this latest form of the invention. Chamber  77  is located immediately above connector segment  78  and intermediate the second, or rearward housing chamber  82  and the third, or forward housing chamber  84 . As will be discussed in greater detail hereinafter, the addition baffle  80  uniquely causes aerosol being drawn from the reservoir bag  56  upon patient inhalation to be accelerated across and around the point of Venturi action in the nebulizer component. This change in air flow creates a reduction in pressure, thereby substantially increasing the rate of fluid aerosolization. By way of example, the addition of this novel airflow baffle incorporates the benefits from both dosimetric/reservoir and breath-enhancement type devices and uniquely decreases patient dosing time to on the order of one to two minutes, when aerosolizing a standard unit dose of Albuterol (2.5 mg/3 m). 
         [0099]    By way of brief background, Dr. John Dennis in “Practical Handbook of Nebulizer Therapy”,  Martin - Derity,  2004, indicates (Page 15) that there are three jet nebulizer designs: Constant output, Breath-enhanced, and dosimetric. As discussed in the incorporated by reference U.S. Pat. No. 5,727,542, the apparatus described therein incorporates a reservoir bag which retains aerosol medication generated during time of patient exhalation for subsequent use during the next inhalation. As such, since essentially all of the nebulizer output is received by the patient, this device is considered “dosimetric” by Dr. Dennis&#39; definition. Further, quoting Dr. Dennis, “breath-enhanced designs operate by allowing air inhaled by the patient to be drawn through the nebulizer, thus “enhancing” the rate of air and aerosol output from the nebulizer during inhalation. On expiration, the output from the nebulizer falls back to a lower rate”. 
         [0100]    As previously mentioned, through the addition baffle  80  to intermediate chamber  77 , the apparatus of this latest form of the invention uniquely combines the features of breath-enhancement devices with the dosimetric/reservoir type devices. The present inventor is unaware of any prior art device that incorporates into a single device the desirable features of dosimetric/reservoir and breath-enhancement. Such a clinical device should prove to be extremely beneficial by shortening patient treatment times, thereby overcoming patient non-compliance issues. 
         [0101]    In using the apparatus of the invention, the nebulizer unit is interconnected with the mouthpiece assembly by telescopically inserting the upper portion of the tapered sidewall  16   c  of the nebulizer unit into connecter  76  of the mouthpiece assembly in the manner shown in  FIG. 19  of the drawings. Following removal of the lower closure assembly  26  of the nebulizer unit, the fluid flow tube  24  is interconnected with the source of gas under pressure, namely tank T ( FIGS. 17 and 19 ). As illustrated in  FIG. 19 , the gas flowing through the gas inlet port  76  in the direction of the arrow  83  passes through the very small nebulizer orifice  28  provided in the nebulizer body  24 . As before, as the gas courses upwardly through the fluid flow tube  24  it creates a partial vacuum in the circumferentially spaced fluid passageways  25 . This vacuum causes the level of the liquid medicaments in the reservoir  18  to flow into passageways  25  and then to flow over the top of the fluid passageways  25 . Due to the basic design of the nebulizer, when the stream of gas flowing through the fluid flow tube strikes the liquid drawn from the reservoir it will be predictably converted into a fine mist containing a mixture of particles of aerosolized medication of varying sizes that will be carried upwardly through spray orifice  22   a  formed in plastic nebulizer body  22 . 
         [0102]    After flowing through orifice  22   a , the fine particulate-laden mist following impact with the selector element  22   b  will flow into expansion chamber  88  of the airflow baffle  80 . As best seen by referring to  FIG. 18  of the drawings, expansion chamber  88  is defined by a generally cylindrically shaped housing  90  having diametrically opposed flow openings  92  provided in the upper portion thereof. Affixed to opposing sides of housing  90  at about 90 degrees from flow openings  92 , are transversely extending baffle walls  94 . As illustrated in  FIGS. 17 and 20 , baffle walls  94  extend across intermediate chamber  77  and one of the diametrically opposed openings  92  communicates with chamber  82  while the other of the diametrically opposed openings  92  communicates with intermediate chamber  77 . As best seen in  FIG. 19 , expansion chamber  88  of the airflow baffle  80  is located immediately above housing connector segment  78  and receives the aerosol spray emitting from the nebulizer in the manner indicated by the arrows  99  of  FIG. 21 . 
         [0103]    Extending downwardly from the top wall of the housing and into chamber  88  of the airflow baffle is a generally cylindrically shaped wall  100 . Wall  100  cooperates with wall  90  of the airflow baffle to define a fluid flow path  102  that receives the aerosol spray flowing into expansion chamber  88  in the direction of the arrows  99 . As indicated by the arrows  105  and  107  of  FIG. 19 , the aerosol flows from flow passageways  102  into chambers  77  and  82  via the opposed openings  92  formed in housing  90  of the airflow baffle (see also  FIG. 20 ). It is this novel configuration of the airflow baffle  80  and its strategic positioning within housing chamber  77  that uniquely causes aerosol being drawn from the reservoir bag  56  upon patient inhalation to be accelerated across and around the point of Venturi action in the nebulizer component. This change in air flow creates a reduction in pressure, thereby substantially increasing the rate of fluid aerosolization. As previously discussed herein, the addition of this novel airflow baffle incorporates the benefits from both dosimetric/reservoir and breath-enhancement type devices and uniquely decreases patient dosing time to on the order of one to two minutes when aerosolizing a standard unit dose of Albuterol (2.5 mg/3 m). 
         [0104]    As the patient inhales, the aerosol flowing from one of the passageways  102  into chamber  77  in the direction of the arrow  105  ( FIG. 19 ) flows through a passageway  108   a  formed in a partition wall  108 , which separates chambers  77  and  84 , through chamber  84  and through breathing tube  63  into the patient&#39;s lungs. As best seen in  FIG. 19 , affixed to wall  108  at a single pivot point  110  is a generally circular substantially flexible flapper valve member  112 . Valve member  112  can be constructed of a number of materials including plastic and various yieldably deformable elastomeric materials. Pivot point  110  is defined by a fastener such as rivet  114  which passes through member  112  at a location proximate its outer periphery and then through partition wall  108 . With this unique construction, fluid passing through passageway  108   a  will cause valve member  112  to open in a novel pivoting motion about pivot point  110 . Conversely, fluid flowing in an opposite direction will cause valve member  112  to securely close and move into sealing engagement with partition wall  108 , thereby blocking fluid flow through passageway  108   a.    
         [0105]    When the apparatus is in use, patient inhalation will cause valve member  112  to open to permit the aerosolized medication to flow from chamber  77  into chamber  84  and then into the patient&#39;s lungs. During the time of patient breath hold and exhalation, the one-way valve will close, causing mist produced during this period of time to be retained within chambers  77  and  82  and within the inflatable bag  56 . This accumulation will fully satisfy the patient&#39;s next breath tidal volume requirements. Once again, this novel construction permits maximum effective use to be made of the particulate-laden mist being generated by the nebulizer. 
         [0106]    In those situations where no harm results from exhalation of the particulate laden mist directly into the atmosphere, a cap  118  which fits securely over a downwardly extending cylindrical portion  120  formed on housing  54  ( FIG. 19 ) is provided, with a small centrally disposed aperture  118   a  which permits flow to atmosphere and at the same time provides sufficient impedance to such flow as to insure proper closing of valve member  112  upon patient exhalation. When member  112  is closed, aerosol emitting from the nebulizer flows through one of the flow passageways  92  in the direction of the arrow  107  and is deposited in reservoir bag  56 . 
         [0107]    The next patient inhalation will not only accept newly produced aerosol from the nebulizer, but now pulls aerosol from the reservoir bag  56 . Knowing that the rate of patient inhalation greatly exceeds the rate of oxygen/air flow to the nebulizer, orifice opening sizes and physical positioning in relation to the point of Venturi action can be tailored to momentarily change internal baffle air pressure to an extent that aerosol generation rate from the nebulizer will more than double. 
         [0108]    Referring next to  FIGS. 23 through 30 , still another form of aerosol inhalation apparatus of the invention is there shown and generally designated by the numeral  124 . This form of the invention is similar in some respects to the apparatus illustrated in  FIGS. 16 through 22  and like numerals are used in  FIGS. 23 through 30  to identify like components. The main difference between this latest form of the invention and the earlier described embodiments comprises the addition of two one-way, umbrella type check valves to the sectionalized main housing  126 . The purpose of these check valves will presently be described. 
         [0109]    Attached to sectionalized main housing  126  is an inflatable bag  56  which is substantially identical in construction and operation to that previously described. Also attached to sectionalized main housing  126  is a nebulizer means, shown here as a nebulizer unit  14  which is also substantially identical in construction and operation to that previously described. 
         [0110]    In this latest embodiment of the invention, a first end  126   a  of the main housing is provided with a standard size breathing port  128  for ready patient interfacing with the aerosol system via a conduit, or breathing tube  63  (see also  FIG. 16 ). As before, the various chambers  130 ,  132  and  134  of the main housing are interconnected by appropriately baffled fluid flow passageways. 
         [0111]    As in the earlier described embodiments of the invention, the nebulizer unit  14  can be pre-filled with the required inhalable liquid medication, used for a single treatment, and then discarded. Carried by a wall  136  of main housing  126 , which is disposed directly above nebulizer  14 , is access means for accessing nebulizer  14  to supply medication fluid to reservoir portion  18  thereof. As before, the accessing means comprises a self-sealing, penetrable septum  70  which, as shown in  FIG. 23 , is sealably mounted within an aperture  138  provided in top wall  136  of housing  126 . 
         [0112]    Disposed within a first, or intermediate chamber  130  of housing  126 , is the important airflow baffle  80  of this latest form of the invention. Airflow baffle  80  is also substantially identical in construction and operation to that previously described and uniquely causes aerosol being drawn from the reservoir bag  56  upon patient inhalation to be accelerated across and around the point of Venturi action in the nebulizer component. Chamber  130  is located immediately above the nebulizer connector segment  78  and intermediate the second, or rearward housing chamber  140  and the third, or forward housing chamber  142  to which the breathing tube  63  is connected. 
         [0113]    Referring particularly to  FIG. 23 , it is to be observed that there are three possible sources of air/oxygen for fulfilling the lung capacity requirement of the patient. These include (1) the gas driving the nebulizer  14 , (2) medicated air/oxygen from the reservoir bag  56 , and (3) possible room air, drawn inwardly through exit port  143  provided in top wall  136  of housing  126 . ( FIGS. 22 and 23 ) Knowing that momentary breath inhale requirements can reach a rate of perhaps 20 liters per minute (LPM) or greater, it is obvious that upon occasion there can be air-entrainment through the exit port  143 . Any such air going to the patient reduces the velocity of air/oxygen drawn from the reservoir bag, thereby decreasing the desirable breath enhancement features. As illustrated in  FIG. 23 , a one-way valve umbrella type check valve  147  placed proximate the exit port  143  eliminates this possibility of air entrainment. Placement of a second one way umbrella type check valve  149  in the outlet port  150  provided in forward chamber  134  is such that if needed to fulfill patient momentary requirements, room air can be entrained. This air, however, will be added to that drawn from reservoir bag  56 , further increasing the desirable breath enhancement features. 
         [0114]    Having now described the invention in detail in accordance with the requirements of the patent statues, those skilled in this art will have no difficulty in making changes and modifications in the individual parts or their relative assembly in order to meet specific requirements or conditions. Such changes and modifications may be made without departing from the scope and spirit of the invention, as set forth in the following claims: