Inhalation Breath Assistant Apparatus And Method for Assisting in Inhalation Thera¬ pies BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to the field of pulmonary drug delivery. It is particularly well- suited, for, but is by no means limited to, delivery of blood glucose lowering agents and hor¬ mones (e.g. insulin) in diabetic patients via a pulmonary route. It may be used with any sys¬ tem or treatment regimen that requires inhalation of a medication and is particularly useful not only where inhalation of a precise dose is desired, but also where absorption into the pa- tient's circulatory system of a precise, controlled dose is desired or necessary. Of course, the stringency of the needed precision will vary with the ailment being treated. Background Many conditions require periodic self administration of medications. While in most cases oral administration of a medication is probably most convenient for a patient, there are many medications, such as insulin, that are not capable of being administered orally. One alterna¬ tive route of administration is a pulmonary route in which a patient inhales a liquid or pow¬ dered medicine, usually in an aerosol form. While conventional inhalers and nebulizers are often used to treat lung and breathing aliments, the ability to systematically deliver a con¬ trolled, consistent and precise dose of medication to a patient's circulatory system through the patient's lungs has proven more difficult. It is often not enough to merely delivery the same dose to the patient's lungs. To get a consistent and controlled dose absorbed often requires breath control, as well as controlling parameters of the aerosolized formulation.

Various inhalation devices exist that aid in depositing a liquid aerosol or dry aerosol powder into a patient's lungs. For example, US patent 5888477 (which is hereby incorporated by reference in its entirety) discloses an inhaler with robust features that may be used for insulin delivery. US patent 5785049 to Smith et al. (which is hereby incorporated by reference in its entirety) discloses a device suitable for powdered medication delivery. These devices, how¬ ever, do not provide feedback to the patient after the drug is released into the device and/or the patient's airway.

SUMMARY OF THE INVENTION The present invention provides a method and system for assisting a patient in absorbing a controlled and repeatable dose of medication into the patient's circulatory system by assist¬ ing the patient in inhaling the medication in a manner that allows for a precise enough dose to be absorbed by the patient's circulatory system so that effective treatment can occur.

In one aspect, the present invention aids in consistent and controlled drug absorption that is administered via a pulmonary route, by teaching a patient to inhale sufficient air after the drug is released a portable inhalation device from which the patient is inhaling. Sufficient chaser air is critical in some cases to ensuring consistent and repeatable dosing. In addition to chaser air volume, the flow rate at which it is inhaled and the point at which medication is released into the device and/or patient's air way can be monitored and reported to the pa¬ tient. This feedback can assist the patient in performing inhalation therapy of medications, such as for example, insulin in a more effective manner.

In one embodiment, the present invention takes the form of a software tool running on a PC that reads out the air flow data generated in an inhalation device or a training device and dis¬ plays them on a screen.

For some medications, consistent and repeatable dosing methods also require that a patient chase the medication with sufficient chaser air after inhaling the medication. Thus, it is de- sirable to instruct or prompt the patient to continue to inhale after drug release occurs. In some cases, the patient should be instructed or coached to inhale a particular predetermined minimum volume at a particular flow rate. For other medications, the flow rate may not be as critical. Moreover, the flow rate and volume required for the chaser may, in some cases, vary with properties of the aerosol, such as particle size, density, etc, as well as from patient to patient.

According to an embodiment of the present invention, the patient inhales a medication from an inhaler, such as the ones described in more detail below. The inhaler may be handheld size for convenience. If the patient achieves a target flow rate and volume, the device re¬ leases the medication in aerosol form. (If the device is being used for training purposes, ac¬ tual medication is not released.) The patient is then instructed to continue inhaling after medication release until a sufficient chaser volume has been inhaled.

The instruction may take the form of a visual display on either the inhalation device or on a device, such as a PC, PDA, or the like, that is interfaced with the inhalation device. The in¬ halation device or the interfaced device preferably includes a means for recording a charac¬ terization of the inspiratory flow profile for the patient which is possible by including a micro¬ processor in combination with a read/write memory means and a flow measurement trans- ducer. With some devices that may be used in accordance with the present invention, it is possible to change the firing threshold at any time in response to an analysis of the patient's inspiratory flow profile, and it is also possible to record drug dosing events over time.

In some embodiments, drug release may occur within an inhaler from the instant (or there- abouts) that the patient begins inhaling from the device. In this case, the chaser volume is the air inhaled from the moment that the patient begins inhaling from the device. Thus, the chaser may start out having a high concentration of medicine to air and the concentration may decrease as the volume of chaser air that is inhaled increases. In fact, in some cases the concentration of medicine in the chaser may approach or become zero by the end of the inhalation of the chaser volume. Thus, while the chaser may be pure air, in most cases it will be a combination of air and medicine where the concentration of medicine declines as the inhaled volume of the chaser increases.

In order to assist a patient carrying out the methods of the present invention, applicants dis¬ close herewith exemplary novel and non-obvious devices and systems that will assist the pa- tient. In one such exemplary embodiment, an inhalation device such as the one described in US Patent No 5888477, which is hereby incorporated by reference in its entirety, is con¬ nected to a personal computer having a display. The outputs of the inhalation device tracks flow rate and volume, as well as when the inhalation device is programmed to trigger release of a drug. In this embodiment, the personal computer processes the data with software and the patient is provided with a display that displays, based on measured parameters from the device, flow rate and volume. The display can display flow rate and volume from start of in¬ halation up to trigger of drug release and then continue to display flow rate and chaser vol¬ ume post drug release. In simpler devices where the aerosol is created prior to inhaling, the display may not show triggering of drug release, as drug administration to the patient starts at nearly the same instant as inhalation starts. In such cases, it is only necessary to display chaser air parameter following the start of inhalation.

Various types of displays may be used in accordance with the present invention. For exam¬ ple, a display might be integral with the inhalation device or can be interfaced with the de- vice. One advantage of interfacing a display with the device is that the display could be used as a training aid in teaching a patient how to breath. The inhaler could then simply monitor the chaser volume without providing feedback for each dose. A PDA, personal computer, etc. would then use its own display to display the information to the patient and/or health care provider. In some cases, the inhalation device can could provide continuous or periodic feedback as to whether a patient is inhaling adequate chaser air. This information might be readily displayable on the device or can be transmitted to another device for display. If the patient is failing to achieve adequate chaser volume, the patient can plug the inhalation de¬ vice into a monitoring system that shows the patient's inspiratory profile and train further.

In one embodiment, when the patient starts inhaling a curve is draw real-time on the screen depending on the flow and volume, The screen may shows a diagram where x-axis marks volume since the start of inhalation and the y-axis marks the airflow through a device in vol¬ ume (Liter pr. minute).

The patient is visually assisted in reaching the correct inhalation flow at the right time so that a release of the medication takes place. The background may be static and comprise multi dimensional system of co-ordinates and a box marking the defined release window (Trigger box) where the drug is released. The screen also shows an ideal inhalation zone marked as a curve that serves as a target curve for the patient.

While a sophisticated display might be used to plot flow rate and volume, simpler displays using a series of LED, lights, sounds, etc that guide a patient to inhale a predetermined vol¬ ume after drug administration begins, will also work in many situations and are easily incor¬ porated into an inhalation device or a device that is interface able with an inhalation device.

In one embodiment, the present invention is well-suited for use in a dose response study. It can be used to ensure whether a dose is properly delivered. This way, only patients who are capable of correct dose delivery into the lungs are promoted to a response part of the trial. This helps to ensure that the population participating in a clinical trial are well-suited for that trail and that ambiguous results due to improper inhalation technique are eliminated. More¬ over, by giving the patients guidance during inhalation, drop out rate due to non-compliant inhalation technique is minimized.

In other clinical studies the benefit would be that it potentially is easier to establish a coher¬ ence btw, patient outcome (little or no changes in Blood Glucose levels) and under dosing due to incorrect inhalation technique.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a display for use with an embodiment of the present invention Figure 2 shows the display with patient data wherein the patient has successfully performed an inhalation. Figure 3 shows the display where the patient failed to hit the target for drug release Figure 4 shows the display with patient data for a patient hat failed to inhale sufficient chaser volume. Figure 5 shows a prior art an inhalation device suitable for delivering a drug via a pulmonary route.

DETAILED DESCRIPTION OF THE INVENTION Numerous devices exist for administering a drug or medication to a patient via a pulmonary route. In many cases getting the medication or drug into a patient's lungs is only half the bat- tie. The manner in which it gets deposited in the lungs, as well as the properties of the parti¬ cles and formulations often play a big part in determining how it will ultimately be absorbed, and for many medications (such as for example insulin) precision of dose size reaching the circulatory system are critical.

One factor that appears to greatly influence repeatability is breath control. See e.g., US Pat. No 5888477. But thus far, the emphasis has been on instruction prior to medication release. Applicants have now shown that breath control after administration also appears to greatly influence repeatability and absorption. It has now been shown that after a medication is re¬ leased into the airway of a patient, the quantity of air the patient inhales after drug release (hereinafter "chaser air") affects absorption and/or repeatability. In some situations, the rate at which the chaser air, as well as the volume of the chaser air, is also critical. While repeatability and precision are required, repeatable may not always require precisely the exact quantity of drug delivered. In some cases, such as in insulin therapy, it is sufficient that the quantity delivered in each dosing episode be sufficient to result in adequate blood glucose control within a medically acceptable range.

Various existing devices may be used to delivery a medication, such as insulin, to a patient's pulmonary system and ultimately to a patient's circulatory system. The Aerx device de¬ scribed in US Pat. No 5888477 is one such device. However, this device, like the numerous other currently available, do not provide feed back to a patient or guidance regarding chaser air inhaled after drug release from the device.

The device and methods described herein are also particularly well-suited for, but by no means limited to, treating diabetes. The methodology for using the present invention for such treatment is also discussed in further detail below. This device can be modified to prac- tice various aspects of the present invention or can be interfaced with a separate device that is configured and operates in accordance with one or more aspects of the present invention. TREATMENT OF DIABETES Diabetes mellitus and many other conditions are generally treated by the injection of agents, such as for example insulin. The present invention provides effective alternatives to injection therapy. For example insulin can be aerosolized and administered to a patient's pulmonary system. Of course, successful treatment may require precise, controlled, and repeatable dose reach the circulatory system of the patient. Exact precision and control is not always required, but in general a treatment needs some level of predictability and repeatability to be effective. When insulin is deposited on the mucus membranes of the respiratory tract, it is absorbed by the body. The repeat and predictability of absorbtion depend upon many things. Some parameters include how fine the particles are, how deep they penetrate into the pul¬ monary system and how difficult the pulmonary system finds it to reject these particles. It has been shown that some form of coached breathing can be beneficial in increase the pre¬ dictability of insulin absorption. For example, some inhalation devices require the patient's inspiratory flow rate and or volume to be within targeted ranges before the device will start drug delivery. However, these devices often provide little feedback or coaching after they release the drug. Applicants have discovered that breath control after drug release can play a critical role in achieving repeatable and controlled delivery of insulin to the patient's circula¬ tory system.

EXAMPLARY INHALATION DEVICE FOR USE WITH THE PRESENT INVENTION

One device that is well-suited for insulin delivery is the Aerx IDMS device described in US Patent No. 5888477, which is hereby incorporated by reference. An inhalation device that may be used with the present invention can be configured as is shown in Figure 5. All com- ponents are within a single, hand-held, portable breath actuated device. A microprocessor 26 and flow sensor 31 are used to provide electronic breath actuated release of a drug, such as insulin. The device includes a holding means and a mechanical means and may operate electronically., i.e. the actuation means is preferably not directly released by the user. The patient inhales through inspiratory flow path 29 which can form a mouth piece 30. Air enters the device via opening 38. The inhaling is carried out in order to obtain a metering event us¬ ing differential pressure transducer 37. Further, when the inspiratory flow meets a threshold of a pre selected criteria, the microprocessor 26 sends a signal to an actuator to release the electrical mechanism 28 which in turn actuates a mechanical means 23, thereby releasing a spring 22 and a plate 24 or equivalent thereof, forcing aerosolized formulation into the chan¬ nel 11 and out of membrane 3 into the flow path 29 where the air surrounding the particles is optionally heated by the air heater 14. Microprocessor 26 of FIG. 5 includes an external non-volatile read/write memory subsystem, peripheral devices to support this memory system, reset circuit, a clock oscillator, a data ac¬ quisition subsystem and a visual annunciator subsystem. The discrete components are con¬ ventional parts which have input and output pins configured in a conventional manner with the connections being made in accordance with instructions provided by the device manufac- turers. The microprocessor used in connection with the device of the invention is designed and programmed specifically so as to provide controlled and repeatable amounts of insulin to a patient upon actuation. The microprocessor should have sufficient capacity to make calcu¬ lations in real time. Adjustments can be made in the program so that when the patient's inspi¬ rator/ flow profile is changed such is taken into consideration. This can be done by allowing the patient to inhale through the device as a test (monitoring event) in order to measure air flow with preferred drug delivery points determined based on the results of several inhala¬ tions by each particular patient. This process can be readily repeated when the inspiratory flow profile is changed for whatever reason. When the patient's lung function has decreased the program will automatically back down in terms of the threshold levels required for release of drug. This "back down" function insures drug delivery to a patient in need but with impaired lung function. Determination of optimal drug delivery points in the inspiratory flow can be done at each dosing event, daily, weekly, or with the replacement of a new cellular array in the device.

The microprocessor 26, along with its associated peripheral devices, can be programmed so as to prevent triggering the actuation mechanism 28 more than a given number of times within a given period of time. This feature makes it possible to prevent overdosing the pa¬ tient. The overdose prevention feature can be particularly designed with each individual pa¬ tient in mind or designed with particular groups of patients in mind. For example, the micro¬ processor can be programmed so as to prevent the release of more than approximately 30 units of insulin per day when the patient is normally dosed with approximately 25 units of in¬ sulin drug per day. The device can be designed to switch off this lock-out function so that in¬ sulin can be delivered in an emergency situation.

The microprocessor 26 of the invention can be connected to external devices permitting ex- ternal information to be transferred into the microprocessor of the invention and stored within the non-volatile read/write memory available to the microprocessor. The microprocessor of the invention can then change its drug delivery behavior based on this information trans¬ ferred from external devices. All of the features of the invention may be provided in a port¬ able, programmable, battery-powered, hand-held device for patient use which has a size which compares favorably with existing metered dose inhaler devices.

The microprocessor 26 can also be programmed so as to allow for monitoring and recording data from the inspiratory flow monitor without delivering drug. This is done in order to charac¬ terize the patient's inspiratory flow profile in a given number of monitoring events, which monitoring events preferably occur prior to dosing events. After carrying out a monitoring event, the preferred point within the inspiratory cycle for drug delivery can be calculated. This calculated point is a function of measured inspiratory flow rate as well as calculated cumula¬ tive inspiratory flow volume. This information is stored and used to allow activation of the electronic actuation means when the inhalation cycle is repeated during the dosing event. In addition, data regarding chaser air can be collected, stored and analyzed.

While this device is well-suited for drug delivery, the device can be used as a sensor alone and either incorporated with the present invention or interfaced with a separate device capa¬ ble of carrying out the present invention. While the present invention is well-suited for use with sophisticated inhalers, such as the one described above, it is possible to adapt basic powder inhalers, such as the ones de¬ scribed in US Patent No 5888477 for use with the present invention. In which case, chaser volume would be the volume of air inhaled after medication starts flowing to the patient's lungs.

EXAMPLARY FEEDBACK PROVIDED VIA THE PRESENT INVENTION Regardless of the type of inhalation device used, feedback to the patient about the volume of air inhaled after drug release, i.e. chaser air, can greatly assist the patient in improving re- peatable, consistent, and precise dosing. In the case of the Aerx device, or other electroni¬ cally controlled inhalation devices, the present invention can be incorporated into the device by providing it with a display and/or processor to provide feedback to a patient and/or health care provider regarding chaser air inhaled after the device starts flowing medication to the patient. Or the device can also be interfaced with a processor and/or display, such as a PDA, computer, or the like, which can then be programmed to display feed back to the pa¬ tient. The feedback can either be given to the patient during every dosing event or can be incorporated only during patient training. Of course, if the present invention is merely used for patient training, a separate device or several interfaced devices can be configured to measure inspiratory profiles, show where drug release will occur and show chaser air pa¬ rameters for air inhaled after drug release.

As is shown in Figure 1 , one embodiment of the present invention might include a display that can take the form of a vertical and horizontal axis with flow rate displayed on the vertical axis 200 and total volume on the horizontal axis 300. This display might be incorporated into an actual inhalation device, such as the one described above, it might be part of a training unit to teach a patient proper inhalation technique, or it might be incorporated into software running on a PC, PDA, or the like that is interfaced with an inhaler and utilizes data collected and/or measured by the inhaler. The display and a corresponding processor can be pro¬ grammed and display other information, such as trial, site, investigator, subject, date, and time. The display might also provide an indication that the patient is ready to inhale, such as the one shown in the box 100. An upper limit for the flow rate 400 and a lower limit 500 may also be displayed. Window 600 shows the target for flow rate and volume that must be achieved before drug release from the device will occur.

Figure 2 shows an example of patient data displayed within the context of the display of Fig¬ ure 1. The patient inhalation follows curve 900. If the patient's inspiratory flow profile hits the target window 600, medication is released. The patient is instructed to keep inhaling, pref- erably within the upper and lower flow rate limits, 400, 500 until sufficient chaser volume is attained.

Figure 3 illustrates an embodiment of the present invention where a patient fails to achieve the target for drug release from the device. Here the patient is prompted to try again. Figure 4 illustrates where a patient has hit the target for drug release, but does not achieve sufficient chaser volume. When the present invention is used as a training apparatus, the patient is instructed to schedule further training. In some embodiments, it may be possible to correlate chaser air inhaled with the quantity of drug absorbed. Accordingly, where the pa- tient has an unsuccessful inhalation, the patient may be prompted to supplement the last dose with more drug, more frequent blood glucose monitoring, or some other action.