Patent Application
20050066968
This invention relates to the generation of aerosols and their delivery to and monitoring within respiratory and other flows for diagnostic and therapeutic purposes. The invention is more particularly directed to the generation of aerosol boli and their delivery under controlled conditions to a site within the respiratory system and more particularly to a pulmonary use site. Deliveries to other medical and non-medical use sites are also enabled by the present invention.
It is well known that a substantial fraction, perhaps 20%, of the world population suffers from respiratory ailments or dysfunctions. Asthma is a serious problem and is becoming more prevalent. Other ailments comprise common allergenic reactions or more serious medical conditions. Treatment of these ailments often involves the periodic (timed) administration of an aerosolized dose of a medicament to the patient via the patient's respiratory tract. By medicament is meant the active and inert, if any, components of a therapeutic drug prescribed by a physician on the basis of presented and/or diagnosed symptoms. Common inhalers are one example of this mode of introduction of aerosolized medicament to the respiratory tract of a patient.
Whereas the prior art methods and apparatus for treatment of diagnosed respiratory/pulmonary ailments or dysfunctions are useful, they suffer from problems associated with inadequate diagnoses, with inconsistent quantities of medicament being dosed, with inefficient deliveries to the diseased site(s), and the timing of the dosage relative to pulmonary inflow, and with patient compliance, among other concerns or problems. In certain instances, dosage can be critical in that (a) the treatment requires some minimum level of medicament for its effectiveness or (b) certain medicaments can be damaging or even lethal if administered in an excessive dosage. Of particular concern is the clinical laboratory setting in which a known quantity of a medicament desirably is inhaled by a patient repetitively and with known, meaning monitored and documented, accuracy and precision for diagnostic or therapeutic purposes. Of greater concern is non-supervised or self-treatment in a home setting; patient compliance and accuracy and precision of the proper drug to the proper site are major issues here.
Another background need arises from the rising preference for administration of certain drugs via the respiratory path, such as insulin, for example. In this case the therapeutic benefits of the medicament lie outside the respiratory tract, but their administration is preferably via the respiratory process. Improved methods and apparatus are essential for such treatments and are enabled by the present invention.
In accordance with one aspect of the present invention, a measured quantity or dose of a medicament in the form of an aerosol bolus is generated by a bolus generator and introduced into the inspiratory flow stream of a patient. Such introductions may be at one or more times or volumes within an inspiratory portion of a breathing cycle, hence at one or more points in the inspiratory volume. Of those aerosolized particles which are delivered to the patient's respiratory tract all or a portion thereof may be deposited at a location or region within the respiratory tract, such as within the pulmonary system, and any non-deposited particles are exhaled by the action of the patient's expiratory breathing flow.
The present inventors have found that the identification of the deposition site of those aerosol particles which are deposited within the respiratory tract is strongly influenced by the timing of the bolus introduction into the inspiratory flow and by the size distribution of the aerosolized particles in the bolus.
In accordance with the present invention, in the course of a breathing cycle of the patient, numerous properties of the medicament, i.e., the aerosol bolus, and fluidynamic and other properties of the inspiratory and expiratory flows, and/or other useful information are measured and used for optimal control of subsequent dosages. The measured aerosol and air flow data are employed to control subsequent delivery of boli to the patient, including the type of medicament, dosage amount, particle size distribution, and the timing of the delivery of each bolus with respect to the inflow, among other things. Patient compliance and treatment regimen are stored for examination by medical personnel either in the clinical laboratory or remotely, over the internet, if, for example, treatment is in a home or small clinic setting. Treatment regimen may be supervised and/or altered locally or remotely.
The present invention is applicable and useful in both therapeutic treatment of a patient and in diagnosing an ailment. In a diagnostic embodiment of the present invention, challenge or diagnostic aerosols are generated and delivered to the patient's respiratory inflow and the fluidynamic properties and the aerosol properties are jointly monitored, as above for the therapeutic embodiment. Indeed, the apparatus is in many cases the same. In this diagnostic embodiment, the aerosol and air flow characteristics are carefully monitored and recorded, and characteristic waveforms similar to an electrocardiograph (EKG) or electroencephligraph (EEG) are presented. From these charts physicians may advantageously perform diagnoses of respiratory function, for example.
In an extension and/or combination of the therapeutic and diagnostics embodiments, automated, on-going diagnoses may be interspersed with therapeutics to optimize treatment according to a predetermined treatment regimen prescribed by the physician.
For present purposes, in a human respiratory environment, an aerosol bolus may be defined as a small volume of gas, ranging from microLiters to Liters, with typical bolus volume in the order of magnitude of approximately 1 milliliter, in which aerosols are added or “seeded” for subsequent transport and delivery. In most cases the aerosol sizes will correspond to inhalable or respirable particles, those typically in the range of 1 to about 10 um in aerodynamic equivalent diameter, but some cases require larger particles, notably upper respiratory tract diagnostics/treatments. Each such bolus is thus a localized, two or more component fluid, i.e., one or more components of gas, typically air, and one or more components of aerosols. Aerosols are liquid or solid particles which are generated from liquid, powder, or a combination of liquid and powder, feedstocks. Aerosol mass concentration is high centrally of the bolus and approaches zero toward its perimeter.
For illustrative purposes, aerosol boli, for introduction into inspiratory flows, may be further characterized as having mass concentrations of 1000 μg/L=1 g/m3, “respirable” particle size of order 1 μm diameter, and mass density=1.5 g/mL particles. The gas component of the bolus volume of 1.0 mL would normally be clean air, at standard temperature and pressure, and with 65% relative humidity. Further, within a bolus, the entrained particles may be monodisperse (i.e., the individual particles are of approximately the same diameter) or polydisperse (i.e., the individual particles exhibit a range of particle diameters).
It is to be noted that these introductory or inhaled aerosol characteristics are modified upon the aerosol (or a portion thereof) passing through the respiratory system and exhaled. These modifications are monitored in the expiratory flow. The more qualitatively evident of these modifications are losses within the respiratory system, particularly size-dependent losses, and changes in shape of the bolus concentration profile. Importantly, these modifications are different between normal and respiratory-compromised persons and for this, and other reasons, it is of importance to have a knowledge of these modifications for diagnostic and for therapeutic purposes, and/or for purposes of optimally controlling the characteristics of boli introduced into inspiratory flows.
Various parameters relating to the bolus and respiratory flows are monitored as the bolus passes from their source and into the breathing tube. In one embodiment, for example, the aerosol mass concentration and the aerosol particle size distribution are monitored as functions of time along with the inspiratory and expiratory volumetric flow rates. Representative electrical signals of each of these parameters are generated and fed to a controller, such as a microprocessor. Further, the direction of flow of the gaseous medium moving through the breathing tube is also monitored and an electrical signal representative of whether the flow is associated with inspiration or expiration by the patient is developed and fed to the controller.
Upon that expiration of the patient immediately following the inspiration of the bolus last inhaled, the flow of breath from the patient is detected and analyzed for parameters such as aerosol mass concentration, particle size distribution (taking into account particle growth in the nearly 100% RH environment of the lung), and volumetric flow, importantly, all as functions of time. Comparison of the data collected from monitoring the inflow of the aerosolized bolus and from monitoring that outflow of air from the patient upon that expiration action which first occurs after a given inhalation action, provides information on any of several results, including, for example, that quantity of the inhaled bolus which remained within the patient's respiratory tract during the observed breathing cycle. Notably, the present analysis is performed on a bolus by bolus basis, thereby providing valuable information on the efficiency of administration of the medicament and other information such as patient compliance. It may be appreciated that these and other data indicate the interactions of the aerosol bolus within the patient's pulmonary tract and, thereby, the performance thereof. It follows that the bolus generator characteristics may be controlled to optimize diagnostics or therapeutics.
Employing the electrical signals fed to the controller, the controller generates an electrical signal which is fed to one or more fast-acting solenoid valves, for example, which control the flow of pressurized fluid into a receptacle or “pocket” containing a measured quantity of the substance to be aerosolized, thereby controlling the timing of discharge of a bolus into the patient's respiratory system.
As desired, other parameters may be monitored, such as the temperature, pressure, relative humidity, etc. of the inspiratory and expiratory flow created by the patient's breathing action. And all such monitored parameters may be recorded and communicated for supervision and intervention, locally in a clinical setting, or remotely, over the internet, for home or small clinic settings.
Referring to
The medicament delivery subassembly 52 of
The disc 56 is mounted for rotation about a vertical axis as defined by the vertical shaft 76 of a motor 78. The motor 78 is chosen to be of a stepper type which is capable of incremental rotational movement to thereby position one of the pockets 60 over and in registered operative relationship to a tube 80 that is in fluid communication between the flow channel 72 of a pocket and a source of pressurized air 82 as by a conduit 84. Interposed along the length of the conduit 84, there is provided a pressure regulator 88 and a pressure gauge 86 or electronic pressure sensor. A fast-acting solenoid valve 90 is interposed between the conduit 84 and the tube 80 for control over the timing and quantity of pressurized air to be admitted through the tube 80 and the flow channel 72 of a pocket disposed in registration with the tube 80. Power and control signals for actuation of the solenoid valve 90 are supplied from the controller 40. As desired, the turntable 56 may be enclosed to the extent desired as by a housing 96.
Referring yet to
Further, as seen in
Within the mixing/stilling vessel 26, as noted, the highly energetic expansive bolus 114 effectively “explodes” into a conical geometry upon its entry into the mixing/stilling vessel. This action effectively disperses the medicament within the mixing/stilling vessel, while simultaneously permitting the entrained particles of the medicament to lose at least a major portion of their initial velocity, along with reduction in the velocity of the impulsively-supplied, aerosolizing gas via tube 80. This action comprises a “stilling” effect that tends to allow the particles of the medicament to “float”? within the interior volume of the mixing/stilling vessel and assume a substantially uniform distribution of aerosol mass concentration of such particles within the upper interior volume 120 of the mixing/stilling vessel, particularly near the exit 24 of the mixing/stilling vessel. It can thus be seen that the vessel 26 further serves as a reservoir, from which boli 32 are ejected.
Further, if the aerosol contains excessively large particles, or agglomerates, the mixing/stilling vessel also serves to classify, by vertical elutriation. That is, aerosols whose aerodynamic equivalent diameters exceed the size supported by the upward flow within the vessel will not ascend the column of gas defined in the interior of the vessel 26 and thus will be classified out of the effluent from the exit 24. The maximum size allowed to reach the output 24 is controlled by the average gas velocity inside chamber 26 which is in turn controlled by the cross sectional area and total gas volumetric flow rate, primarily by flows 110,112.
The exit end 24 from the mixing/stilling vessel is depicted in
The controller 40 may comprise internally one or more microprocessors, personal computers or programmable logic controllers (PLCS) 128, as all are well known in the art. Inputs to and outputs from controller 40 are fed to a stand-alone supervisory personal computer 130. If desired, outputs from the supervisory personal computer 130 may be fed to a “main frame” computer in the event additional processing capacity or speed of processing is needed or desired.
Within the controller 40, the various electrical signals are processed to provide multiple output signals. Some of these signals are employed to provide visual display of one or more of the data products generated by the individual monitoring elements of the present system, or of the results of calculations performed within the controller using the input signals from the monitor and/or other data, such as time between events, etc. It will be noted that the input/output (I/O) requirements of both the controller 40 and the personal computer 130 are extensive and robust performance is essential. The control features of the invention are further explained hereinafter.
In the present invention, it is desired that a prescribed and measured quantity, bolus by bolus, of a medicament be delivered by bolus generator 2 for subsequent delivery to a patient 12 for inhalation thereof during the inspiration portion of the patient's breathing cycle. Once the internal volume of the mixing/stilling vessel is substantially filled with aerosolized particles of the medicament, or once the aerosol mass concentration near the exit 24 of the bolus generator 2 approaches equilibrium, any subsequent introduction of gas into mixing/stilling chamber 26, whether additional medicament is introduced or not, will result in the expulsion of substantially equal volume of aerosolized medicament in a bolus from the exit 24 of the mixing/stilling vessel 26. It will be recognized that the rate of expulsion time of the stated volume of aerosolized medicament bolus 32. which may be on the order of hundreds of ms, will be a longer period of time than the time required to introduce the stated volume of medicament and pressurized air into the mixing/stilling vessel, e.g., tens of ms. This is due to the pressure differential between the internal volume of the mixing/stilling vessel relative to the atmosphere pressure. It will also be recognized that impulsive gas flow via solenoid valve 90 or controlling flows via solenoid valve 107 may be used to expel boli from exit 24, without moving disc 58. That is, more than one impulsive, expansive flow 114, without aerosols, may be delivered into the mixing/stilling vessel. Similarly, impulsive volumes of gas, without aerosolized medicament, may be effected by the auxiliary or additional flow 110.
Thus, the mixing/stilling vessel 26 operates to convert the initially violently turbulent inflow of pressurized gas and measured medicament particles in pockets 60 into the internal expansive bolus 114 to a relatively homogeneous concentration of aerosolized medicament particles in a bolus comprised of the aerosol-laden gas exiting exit 24. Accordingly, each such bolus 32 which exits the mixing/stilling vessel 24 comprises a volume which is controlled. Because of the mixing/stilling action within the vessel 26, the number and mass concentration of medicament particles within each exit bolus is controlled by the combined monitoring and controlling actions effected by aerosol monitor 124 and gas flow monitor 122. Thus, controller 40 is able to provide a measure of the quantity and other characteristics of the medicament in a bolus 32 exiting the bolus generator 2 and entering the breathing tube 18 and which is inhaled during the inspiratory portion of the breathing cycle of the patient 12.
It is noted that in one example, the pulsed fluid input to the mixing/stilling vessel results in a pulsed expulsion output of 1.0 mL of medicament and fluid, i.e., the bolus of interest, from the output of the mixing-stilling vessel. This bolus output occurs whether or not a fresh pocket containing additional medicament is presented for aerosolization because of the storage reservoir nature of the mixing/stilling vessel. That is, the gas volume entering the mixing/stilling vessel may be separately sourced from the impulsive, aerosolizing gas. The timing of the expulsion of a bolus from the mixing/stilling vessel and the quantity and other characteristics of aerosolized medicament contained within the bolus are thus functions of the timing and the quantity of the medicament and its associated entraining fluid entering the mixing/stilling vessel. It will be further recognized that the bolus exiting the mixing/stilling vessel is much lower in mass concentration and much slower in movement than the mass concentration of the medicament in the internal, expansive bolus entering the initial and internal parts of the mixing/stilling vessel. Expansive, aerosolizing boli 14, which are internal to the bolus generator 2 are to be sharply distinguished in their properties from external boli 32 intended for inhalation by a patient in accordance with the present invention.
In one embodiment, the exit from the mixing vessel is connected via a “soft” connection to a breathing tube, for example. In this embodiment, seen in
More specifically, the opposite and distal end 22 of the breathing tube 18 terminates adjacent, but spaced apart from, the exit 24 of a mixing/stilling vessel 26. In
Intermediate the opposite ends of the breathing tube 18 there are provided an aerosol monitor 36 and a flow direction and volumetric flow monitor 37,38 which respectively are capable of generating electrical signals that are representative of the aerosol characteristics, such as mass concentration and particle size distribution and electrical signals that are representative of the volumetric flow rate and direction of inspiratory and expiratory air to and from patient 12. Other fluidynamic data, such as pressure, humidity and the like, and patient data, such as breathing rate, heart rate, blood pressure, and the like, may also be monitored and recorded. Each of the electrical signals from the monitor 36, the flow direction detector and from the volumetric flow monitor are fed to the controller 40.
In
More specifically, in the depicted embodiment, there is provided a rotary table 164 which rotates about a vertical axis 163 and has a plurality of cylindrical cavities 166,168 disposed concentrically of, and spaced inwardly of, the outer circumference 169 of the table 164. The table is mounted for rotation as by a motor 170 such that each of the cavities 166,168 are sequentially movable from a first position in register with the distal end 24 of the exit tube 122 to a second position in which the same cavity is in register with, hence in fluid flow communication with, the flexible breathing tube 162.
In operation of the subassembly 2A, when the cavity 168 is in register with the exit tube 122 of the mixing/stilling vessel, the other of the cavities 166 is in register with the breathing tube 162. When so positioned, the cavity 168 is available to receive therein a quantity of the aerosolized medicament contained within the mixing/stilling vessel upon the injection into the mixing/stilling vessel of a measured quantity of medicament, entrained in air, as further described hereinabove. A filter 172 is provided in fluid flow communication with that end 174, for example, of that cavity 168 which is in register with the exit tube 122 of the mixing/stilling vessel, to permit the expulsion of air from the cavity as the cavity is being filled with the bolus 160. Upon filling of the cavity 168 with the bolus 160, the table is rotated to exchange positions of the cavities 168 and 166, thereby moving the cavity 166 into register with the exit tube 122 and the cavity 168, which contains the bolus 160 in register with the breathing tube 18 and therefore available for inhalation by the patient. The distal end 178 of the breathing tube is open to ambient atmosphere to permit the patient to inhale a full breath of air and to sweep the bolus into the patient's pulmonary system.
As depicted and described hereinabove when discussing
It will also be recognized that the practice of the invention necessitates attention to compactness of all the elements. Particular attention is paid to closely coupling the point of bolus introduction with the patient.
The disclosure hereinabove has focused on the controlled bolus generator subsystem 2, whose purpose is delivery of boli 32 of controlled characteristics for introduction in the respiratory tract of patient 12. The aerosol and gas flow monitoring subsystem 3 and the control and communications subsystem 4, together, monitor and control the actual aerosol mass and size distribution delivered to patient 12, upon inhalation, and received from patient 12, upon exhalation.
The outputs of sensors 36,37,38 are connected, typically bidirectionally, to controller 40, which preferably is a dedicated micro controller-based system. Controller 40 also connects to bolus generator 2, and numerous other devices thereto related, for control of boli 32, as explained at the end of this disclosure. Data about the bolus and flow are sent from controller 40 to PC 130 which also receives other information relative to the diagnostic or therapeutic session in progress, some of it in essentially real time, via internet connections 44, internal main frame 46, and other controllers 132. Video screen 131 is the principle interface for in-clinic staff.
In a scalar analysis applicable to the present system, the rationale for which analysis is fully developed in copending PCT/US00/08354 and PCT/US01/05948, the mass delivery rate of aerosolized medicament to the inspiratory flow of the patient during each breathing cycle is determined by the formula:
dM/dT˜QC mg/sec Eq. 1
All known light scattering particle instrumentation sensors that are applicable to the present invention fall basically into two categories: photometers (or nephelometers) and single particle counters. Photometers respond to a plurality of particles in their scattering volume(s) at any given time and can give an indication proportional to mass concentration provided the particle characteristics are constant. That is, the calibration of photometers depends on particle size distribution, index of refraction, composition and shape of the particles being observed, transport gases, particle velocity and the like. Photometers cannot provide information on particle size. Single particle counters detect and size single particles in their scattering volumes. The strict requirement for no more than one particle in the scattering volume dictates a maximum particle concentration and limits the range in particle sizes that can be accommodated for a particular instrument design. It follows that single particle counters cannot provide mass concentration.
The electro-optical sensor described in the copending PCT patent application PCT/US01/05948 referenced hereinabove is a combination of both the photometer and the particle counter such that the primary data products are (a) accurate mass concentrations (g./L) and, (b) particle size distributions. Furthermore, these primary data products are provided for the inspiratory and expiratory flows and more particularly provide accurate, precise and cost-effective measurements of the mass concentration of relatively fine (mean diameter approximately 1 to 10 um) particles at very high concentrations (1-10,000 g./L) and over relatively short intervals of time (less than 1 ms to 10 s of ms). As a practical matter, making such measurements in view of real world variabilites in particle size distribution and concentration of medicaments intended to be administered via the respiratory tract of a patient and in view of the nearly 100% relative humidity environment encountered by the particles with the pulmonary tract is a difficult task. However difficult, a separate photometer in combination with a separate single particle counter may be used equivalently in the invention provided the performance requirements disclosed herein are met.
The 100% RH environment of the lung causes hygroscopic particles to grow. For certain diagnostic tests, hydrophobic particles are used. If the mass of hygroscopic particles is to be compared or balanced between inspiratory and expiratory flows, the growth must be corrected. Among the usual methods is to dry or desiccate them prior to measurement in the expiratory flow. This may be accomplished by the addition of a quick response heating element between the patient's mouth and the aerosol and flow sensor 36,38 station.
Aerosolized particles in the smaller particle size ranges (of order 1 μm) are primarily useful for accessing the deep alveolar regions of the lung 6 whereas those medicament particles in the larger range (about 10 um) deposit in the upper portion of the respiratory tract or conductive airways. In many diagnostic applications, nearly monodisperse particle size distributions are advantageous. In many therapeutic applications, polydisperse distributions, which are generally less complex, and therefore less expensive, to generate are advantageous. The present invention permits the use of such polydisperse medicaments in that the present invention provides for measurement of the particle size distribution of each bolus employed during each breathing cycle. Knowledge of the particle size distribution of a polydisperse bolus permits one to make comparisons and/or calculations which take into account the polydisperse nature of the particles of the bolus and thereby provide accurate and precise indication of the disposition of the particles within the pulmonary tract of the patient. This disposition includes the quantity of particles of a given particle size, hence their location of disposition within the respiratory system.
Referring to the
Modifications to the bolus, as quantitatively measured in expiratory flow 17, are rich in opportunities for diagnoses of respiratory health.
Note further that the graph for inspired aerosol bolus concentration Ci(t) is a very short, “spiked,” waveform 200, compared to the graph for Qi(t). This is of course related to the small ratio between bolus 32 volume and respired volume, RV, as discussed above. This graph of Ci is characterized by its peak amplitude PI and by its full width at half maximum, WI, where I is associated with inspiration.
Significantly, it will be further appreciated that the qualitative modifications to the inspired bolus 32 waveform Ci 200 explained just above are confirmed in the concentration Ce(t) 201 waveform shown for expiration. Whereas
But whereas the modified bolus waveform Ce 201 upon exhalation is evidently quite different from the inspired bolus Ci 200, it is comparisons of the Ces 201 for normal and compromised persons of similar physiological description that genuinely enable diagnostics. Further, comparisons based on bolus timing, as indicated by Vb 210 and Tb 212, on size distribution and type of diagnostic (or therapeutic) aerosols and the like enable thorough diagnostics and treatments. These comparisons between persons require, of course, that the test or diagnostic aerosols are the same, for a given test procedure or specific part of a given test procedure, in concentrations, size distributions, particle density and shape, and the like. Different test procedures will utilize different aerosols and other procedures, depending upon hypothesized ailment.
Note that a test procedure embodying the present invention may involve a plurality of such tests, which tests as a battery would lead to respiratory performance profile. That is, a plurality of bolus injection timings, Tb 212 or Vb 210, over a range appropriate for the hypothesized ailment, would be executed and in combination would constitute a profile as contemplated in the present invention. One member of the set of waveforms is represented by bolus introduction Ci(t) 200, at Tb 212 or Vb 210 in
Through the monitoring of the mass concentration and particle size distribution of medicament particles in bolus 32 with aerosol sensor 36 within the inspiratory and expiratory flows of breath from the patient, and through monitoring the volumetric flow rate with flow sensor 38 of the inspiratory and expiratory flows, the controller is capable of determining the mass of medicament or challenge aerosol inspired, MI
Another difference between inspired and expired boli is in particle size distribution. Since the deposition of aerosol mass in the respiratory tract is highly dependent upon particle size, it follows that changes in the size distribution between inspired and expired boli are also an indicator of respiratory performance. In some cases, size distribution changes are most sensitive and more robust indicators than total deposited mass MR.
The dosage to the respiratory tract MR may be controlled by controlling the mass introduced upon inspiration, MI, in at least two distinctly different ways, as follows. For example, if the controller 40 senses that the dosage MR has fallen relative to a set point, the controller 40 then increases the bolus 32 volume by increasing the amount of impulsively-supplied displacement gas via solenoid valve 107 until the desired MR is achieved. This is seen to be a fast control action which can operate on a individual bolus basis. Another control action, which is inherently slower, is to increase the equilibrium concentration at the top of mixing/stilling chamber 26, in the vicinity of the tapered section 120. This action is accomplished by increasing the rate at which fresh, filled pockets 66,68 of medicament are introduced to the aerosolizing section 53. The characteristic response time for this control action is related to the time for the equilibrium concentration in the vicinity of the output tapered section 120 to change. These two and other control strategies may of course be used in combination.
For some treatment regimens it is better to simply control the aerosol mass inspired, MI. The same fast, bolus volume and slower, aerosol concentration control actions, or others would be taken.
Of importance in the present invention is the ability of the apparatus to carry out the delivery of at least one bolus having the desired quantity of medicament therein to the patient during the inspiration portion of the patient's breathing cycle, to monitor the inflow and outflow during the breathing cycle, calculate any needed control signals and output such control signals (with or without changes) to the operative components of the present apparatus with the time span of a single breathing cycle of the patient. In general terms, a relaxed normal breathing cycle may consume between 1 and 5 seconds. Further, it will be recognized that two or more bolus generators may be employed to provide two or more boli, of different medicaments or different amounts of the same medicament, etc., to a breathing tube for inhalation by the patient. The later alternative will be recognized as being capable of delivering two boli per inhalation, alternate boli per alternate inhalations, or other similar combinations such as different timings of inhalation of the same medicament per each inhalation, alternation of diagnostic boli with therapeutic boli, etc.
All of the above disclosure has been directed to diagnostics and treatments wherein the patient is able to breathe more or less normally. The invention of course applies to very ill patients for which inspiration and expiration are aided by a ventilator.
The industrial applications of the present invention are as set forth herein above, along with other industrial applications which will be recognized by a person skilled in the art.
| Number | Date | Country | Kind |
|---|---|---|---|
| PCT/US01/05948 | Feb 2001 | WO | international |
This application claims priority based upon pending U.S. Provisional Application Ser. No. 60/222,273, filed Aug. 1, 2000, entitled: METHOD AND APPARATUS FOR GENERATION AND INTRODUCTION OF AEROSOL BOLI INTO INSPIRATORY AND OTHER FLOWS, pending U.S. Provisional Application Ser. No. 60/222,575, filed Aug. 1, 2000, entitled: APPARATUS AND METHOD FOR MEASUREMENT OF AEROSOLIZED PARTICLES INHALED INTO AND EXHALED FROM THE PULMONARY SYSTEM; and pending U.S. Provisional Application Ser. No. 60/251,114, filed Dec. 4, 2000, entitled: METHOD FOR CONTROLLING PHARMACEUTICAL AND OTHER AEROSOL MASS DELIVERIES. Priority is also claimed based upon copending PCT application Serial No. PCT/US01/05948, filed Feb. 22, 2001, entitled MEASUREMENT OF AEROSOL MASS CONCENTRATION AND MASS DELIVERY RATE. Each of the forgoing copending applications is incorporated herein in its entirety by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/US01/24183 | 8/1/2001 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 60222575 | Aug 2000 | US | |
| 60222273 | Jul 2000 | US | |
| 60251114 | Dec 2000 | US |
