Abstract:
A device for the controlled inhalation of therapeutic aerosols comprises means providing individual patient parameters and/or aerosol parameters for the inhalation. The aerosol doses, such as the tidal volume and the respiratory flow, are individually adjusted on the basis of these individual parameters. Thus, the inhalation device may be individually adjusted to the patient to be treated.

Description:
FIELD OF THE INVENTION 
   The present invention relates to a device and a method for the controlled inhalation of therapeutic aerosols and in particular for the individual dosimetry of inhaleable aerosols. 
   BACKGROUND OF THE INVENTION 
   In the inhalation of drugs in form of aerosols, several factors are of importance for the deposition of the active ingredient in the lung. The deposition of the active ingredient in the lung depends on the particle properties of the active ingredient to be inhaled, such as the particle size, electric charge and hygroscopicity, the inhalation velocity (i.e. respiratory flow) of the patient and the inhalation depth (i.e. tidal volume) of a breath of the patient to be treated. 
   In various drugs which are to be inhaled in form of aerosols, the amount of inhaled active ingredient has to be given in extremely accurate doses since any overdose could be critical to the patient. In case of conventional inhalation methods, the particle size is adapted to the drug to be administered. However, the patient&#39;s breathing pattern is not controlled in any way so that the individual dosage may vary strongly. In case of weak breathing (shallow, rapid respiration), the inhaled drug falls short of the recommended dose, whereas heavy breathing (deep, slow respiration) results in an overdose. 
   EP-B-0 587 380 describes a drug delivery arrangement that recognizes an inhalation and administers the drug only during an inhalation phase of the breathing cycle while the patient is free to breathe as he likes. This freedom, however, varies from patient to patient, so that the dosages vary considerably. EP-A-0 965 355 describes a controlled inhalator with a predetermined aerosol volume and a limitation of the respiratory flow. In this inhalator, the respiratory flow and the tidal volume are adjusted within certain limits. However, as a mass product, this inhalator cannot be adapted to the concrete requirements as to the pulmonary function of a specific individual. The parameters adjusted for the tidal volume and the respiratory flow are acceptable for the majority of patients, however, the drug administration for the individual patient is not optimal. 
   Therefore, the following problems occur in practice:
         1. Many very obstructive patients are no longer capable of developing the necessary respiratory flow which they would, however, have to develop for an optimal aerosol application;   2. Many of these patients have only very restricted tidal volumes, above all patients with pulmonary emphysema or patients with very small lung volumes;   3. Every patient inhales at a different rate and with a different volume so that the drug dosage within the lung varies widely.       

   It is the object of the present invention to provide an improved device for a controlled inhalation of therapeutic aerosols. 

   
     DRAWINGS 
       FIG. 1  is a schematic plan view of a programmable memory card for holding patient information. 
       FIG. 2  is a diagram of my inhaler device for accommodating the respiratory characteristics of different patients. 
       FIG. 3  is a diagram showing the adjustment of flow rates for an individual patient. 
       FIG. 4  shows a method of using the inhaler device in an embodiment of the present invention. 
   

   DESCRIPTION OF THE INVENTION 
   The present invention is based on the idea to provide an inhalation device with means offering individual patient parameters and/or aerosol parameters for the inhalation as well as means that adapt the dosage of the aerosol/s as a function of the predetermined individual patient and/or aerosol parameters. Thus, the inhalation device according to the invention may be individually adapted to the patient&#39;s capabilities. 
   According to a first embodiment, the individual parameters are provided on a memory medium  10 , for example on memory media that are available under the designations SmartCard, FlashCard or SmartLabel. The individual parameters are stored in the memory medium  10  for example upon a measurement of the current pulmonary function of the patient  20  (carried out e.g. by the family doctor). According to a first embodiment, the patient  20  then inserts this medium  10  (at home) into the inhalation device  12 , whereupon the individual data are read out. Alternatively, the memory medium  10  is inserted into a separate device from which the individual parameters are transferred to the inhalation device  12 . According to a further alternative embodiment, a modem  14  is provided so that the inhalation device  12  is provided with the individual parameters by the physician or the institution in charge via a data link  16  (for example a telephone line). 
   According to a further embodiment, means for the manual data input of individual parameters are provided, e.g. by the respective keys. Alternatively, in the device  12  according to the invention, the individual parameters are adjusted via manual control units  22 , e.g. potentiometers, or manual switches. 
   Thus, the individual patient and/or aerosol parameters influence the individual dosage of the aerosol/s either manually or automatically (e.g. via a respective valve control). Since the amount of aerosol deposition in certain lung sections dependent on the particle size of the active ingredient, the tidal volume and the respiratory flow is known, the aerosol deposition in the lung can essentially be predetermined according to the present invention. The patient  20  considers the adjusted breathing maneuver agreeable since it is adapted to his/her capabilities. 
   An adjusting means or mechanism adjusts individual aerosol doses administered by the device on the basis of the predetermined individual patient parameters and/or aerosol parameters. The adjusting means adjusts a respiratory flow and/or a tidal volume of the inhalation device by accessing the individual patient parameters and/or aerosol parameters for the inhalation through an input mechanism, and evaluating the parameters. On the basis of those parameters, the adjusting means adjusts respiratory flow and tidal volume of the inhalation device. One example of an adjusting means of the present invention is one or more valves controlling the amount of respiratory flow and tidal volume of the inhalation device. 
   In a preferred embodiment, an adjusting means for adjusting individual aerosol doses on the basis of the predetermined individual patient parameters and/or aerosol parameters by adjusting a respiratory flow and/or a tidal volume of the inhalation device is provided. 
   In a preferred embodiment, each breathing maneuver carried out by the patient  20  is stored on the memory medium  10  of the inhalation device  12  so that the administration may be controlled after a certain period of therapy. 
   In a further preferred embodiment, the memory medium  10  is reprogrammable in order to provide adapted parameters for the correct breathing maneuver if the pulmonary function of the patient  20  changes. 
   Preferably, the inhalation device  12  according to the present invention prevents an overdose, for example by pre-setting an action period or an action blockage, e.g. on the memory medium  10 . This prevents the activation of the inhalation device  12  by the patient  20  as long as the necessary period of time between two successive inhalations has not lapsed. Preferably, the memory medium  10  also serves for recording errors. It records for example whether the atomizer pressure deviates too much from a desired range or whether the required atomizer pressure could not be built up at all. Moreover, the memory medium  10  preferably records a possible safety cutoff when the pressure at the mouthpiece  18  (positive pressure respiration) gets too high. In a further preferred embodiment, a too high deviation of the flow (either the atomizer flow of the aerosol or the auxiliary flow of the additional air supplied to the aerosol air or the sum of both flows) is recorded or an error message if one of the aforementioned flows for the inhalation could not be built up. Preferably, a termination of the inhalation is also recorded by the patient  20 . 
   Preferably, the designation of the drug to be inhaled is also stored on the memory medium  10 . 
   Moreover, according to a preferred embodiment, an access control for servicing is provided. Servicing software in the inhalation device  12  for is activated by means of a specific code in the memory medium  10 . 
   The inhalation device according to the invention offers the following advantages:
         1. For each patient  20 , an individually agreeable and optimal inhalation manoeuvre is adjusted or pre-set;   2. By pre-setting individual parameters, different substances may be applied to different desired areas of the lung;   3. The release of the active ingredient is made more reproducible;   4. The optimal dose of the active ingredient is applied to the desired section of the patient&#39;s lung.   5. By programming different breathing maneuvers, different drugs may be inhaled with one device optimally and individually adapted for each patient  20 ;   6. The inhalation device according to the invention may immediately be updated to new substances, new breathing maneuvers and changed respiratory flows;   7. In a memory medium  10 , such as a SmartCard, breathing maneuvers in the course of a therapy may be recorded and subsequently evaluated;   8. If the patient&#39;s pulmonary function changes, the inhalation device may easily be re-set to the changed basic condition;   9. The use of a propellant is not absolutely necessary.       

   An exemplary inhalation device that can be adapted for purposes of the present invention is disclosed in U.S. Pat. No. 5,161,524 to Evans, the disclosure of which is hereby incorporated by reference. Evans discloses a breath-actuated inhalator having a primary and a secondary air flow conduit. The portable dosage inhalator dispenses to a patient a predetermined amount of a pharmacologically active dry powder compound. The inhalator includes a housing defining an air exit end for insertion into the mouth of a patient. The inhalator also includes a primary air conduit within the housing and defining a venturi within the primary air conduit. The inhalator further includes a secondary air conduit within the housing adjacent the primary air conduit. The inhalator controls air flow velocity therethrough during inhalation by the patient. A regulator normally closes the secondary air conduit to air flow and is adapted to move between a first position where the secondary air conduit is substantially closed and a second position where the secondary air conduit is substantially open in response to air pressure differentials created in the venturi of the primary air conduit as a patient inhales through the air exit end of the housing. 
   According to the invention, all medicinal agents may be used which become effective either topically in the respiratory system or systemically. Suitable medicinal agents are analgesics, anti-angina agents, anti-allergic agents, antihistamines and anti-inflammatory agents, expectorants, antitussives, bronchodilators, diuretics, anticholinergics, corticoids, xanthines, oncotherapeutical agents as well as therapeutically active proteins or peptides, such as insulin and interferon. 
   The administration of medicinal agents for treating respiratory diseases, such as asthma, as well as prophylactics and agents for treating the mucosae of the tracheobronchial system is preferred. The administration of esters of retinol and vitamin A as described in EP-A- 0 352 412 is particularly preferred. The medicinal agents may be in their free form or in form of a pharmaceutically acceptable salt or ester. A further possibility consists in embedding the medicinal agent in liposomes. 
   The medicinal agents may be packaged with conventional, pharmaceutically acceptable excipients.