CZ20002162A3 - Method and apparatus for inhaling a medicament - Google Patents

Abstract

A method and apparatus for providing facial abutment (11) includes a face mask on the patient's face (11, 49, 89) provided with inlet (11a, 49a, 89a) gas, sensor (19, 67, 99) for measuring gas flow sucked in by the inlet (11a, 49a, 89a) of the face mask (11.49, 89), while abutting the face mask (11, 49, 89) on the patient's face is detected by monitoring the gas flow sucked in by the inlet (11a, 49a, 89a) of the face mask (11, 49, 89) when inhaling a patient and the face mask (11, 49, 89) is considered to be on the patient's face if it is regular inhalation wave shape is achieved

Description

Technical field

The invention relates to a method and apparatus for delivering a metered dose of a medicament, in particular a liquid or powder, in a sprayed condition to a patient.

BACKGROUND OF THE INVENTION

A variety of nebulizers and inhalers have already been proposed for administering a drug dispersed in a gas to a patient.

Inhalers are generally divided into two basic categories, one comprising pressurized metered dose inhalers and the other inhaler for dry powder inhalers, both inhalers having mouthpieces through which the patient can inhale the active ingredient. However, the effective use of inhalers can be problematic for many patients, especially pediatric patients.

With traditional inhalers or non-breath actuated inhalers and pressurized metered dose inhalers, these problems are exacerbated because effective handling of the inhalers requires the patient to actuate the inhaler at the very beginning of the inhalation cycle to absorb the effective dose of the drug. deep into the lungs. It is precisely achieving proper coordination of inhaler control with inhalation that is difficult for pediatric patients. In particular, if the pressurized metered dose delivery inhaler is triggered before the inhalation begins, most of the medicament remains trapped in the back of the mouth and if the pressure inhaler is triggered late after inhalation, most of the medicament remains in the mouth or in the bronchial tract where it has no effect.

Breath-actuated pressurized metered dose inhalers do not require such coordination or inhalation, but their use again makes it difficult for children because the patient has to inhale with sufficient force to achieve the necessary air flow, namely 30 1 / min for dry powder inhalers, in which, with pressurized metered dose inhalers, the aerosol container is opened and the dry powder inhalers suck in the air. In particular, pediatric and other weaker patients are unable to inhale the volume required to achieve such flow. For pediatric patients, the respiratory capacity generally ranges from 10 to 150 ml, allowing the generation of an air stream with a flow rate of about 3 to 15 l / min.

WO-A-96/01663 and WO-A-97/07896 disclose examples of devices developed to coordinate aerosol delivery during inhalation to a patient. These devices are adapted to deliver an aerosol based on the detection of an inhalation air stream exceeding a minimum value.

So far, aerosol has been administered to pediatric patients by means of a nebulizer or inhaler combined with an inhalation device. Although both of these systems provide a low-velocity cloud of aerosol that can be inhaled even by pediatric patients, typically in several inhalation phases, the dose received by the patient can vary widely and the patient has no information about the exact dose administered.

This variation in dose is essentially the cause of the requirement for the use of facial masks by pediatric patients, since children, especially younger ones, are unable to effectively grasp the mouthpiece. However, the use of a face mask greatly increases the volume of unused, so-called dead space between the nebulizer or the nozzle and the patient. This problem does not usually occur when using an inhaler by adult patients, as they typically have sufficient respiratory capacity that exceeds the dead space volume behind the nebulizer or extension, and because such a patient's dose may approach the correct degree of accuracy if the inhaled volume is multiplied by gas.

WO-A-96/13294 discloses a method and apparatus for administering a medicament to a patient by inhalation, wherein the medicament is delivered to the chamber prior to inhalation and the total medicament dose received by the patient is calculated from the chamber volume, the amount of medicament delivered to the chamber, elapsed time the medicament into the chamber and the flow rate of the gas drawn into the chamber.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a method and apparatus for more accurately and reliably delivering a metered dose of medicament to a patient having limited respiratory capacity and capable of aspirating air at only slower speeds.

SUMMARY OF THE INVENTION

This object is achieved by a device for securing the face mask to the face of a patient according to the invention, the device comprising a face mask having an inlet through which gas can be drawn in, a sensor for measuring the flow of gas drawn in through the face mask inlet, and an indicator for providing an indication of a sufficient fit of the face mask to the patient's face, wherein the face mask is detected by monitoring the flow of gas drawn in through the face mask upon inhalation of the patient, and the face mask is considered fitted to the patient's face when a regular inhalation waveform is achieved.

In a preferred embodiment of the invention, the device further comprises a chamber provided with an outlet in fluid communication with the face mask inlet.

According to a further preferred embodiment, the chamber is provided with a gas inlet. The face mask inlet includes a one-way valve to prevent exhalation through the inlet.

In another preferred embodiment of the invention, the face mask is provided with an outlet for exhaling gas. This face mask outlet includes a one-way valve to prevent inhalation through the outlet.

Preferably, the indicator includes a display unit for displaying the face mask contact information on the patient's face. The display unit preferably comprises an illuminated LCD display or a liquid crystal LED display.

In a further preferred embodiment of the device, the indicator is formed by an acoustic generator for generating sound after the face mask is sufficiently seated on the patient's face.

The invention also provides a device for delivering a medicament to a patient for inhalation, according to another embodiment of the invention, wherein the device comprises a chamber for temporarily storing the medicament before inhalation, a medicament delivery device, a face mask containing an inhaler for gas inhalation. a storage and calculation device for securing the face mask to the patient ' s face and for calculating the dose of medicament received by the patient, the storage and computing device comprising a sensor for measuring the gas flow drawn from the chamber and the device for determining the drug concentration in the chamber during each inhalation inhalation; decreases over time, at least in part, due to the deposition of the medicament on the inner walls of the chamber, where the abutment of the face mask is determined by monitoring the flow of gas drawn in from the chamber and the total dose of medicament received by the patient is calculated as the sum of the drug doses received at each inhalation inhalation, the drug dose received at each inhalation is calculated as the amount of drug inhaled from the chamber in the inhalation volume after compensating for the device dead space volume behind the chamber.

The face mask inlet preferably comprises a one-way valve to prevent exhalation through the inlet. The face mask is provided with a gas exhalation outlet, the face mask outlet having a one-way valve to prevent inhalation through the outlet.

The storage and calculation device comprises a sensor for detecting the medicament supply to the chamber, the sensor for measuring the flow of gas drawn from the chamber and the sensor for detecting the medicament supply to the chamber are formed by the same sensors.

In another preferred embodiment of the invention, the sensor for measuring the flow of gas drawn from the chamber and the sensor for detecting drug delivery to the chamber are separate sensors.

The sensor for measuring the flow of gas drawn from the chamber is preferably located upstream of the device.

The apparatus further includes a display unit for displaying information about the inhalation waveform, the maximum inhalation wave amplitude, the face mask on the patient's face, the drug concentration in the chamber, the warning signal when the drug concentration in the chamber falls below a predetermined threshold and the dose received. patient. The display unit includes an LCD with glowing LEDs or a liquid crystal LED display.

In a further preferred embodiment of the invention, the device comprises an acoustic generator for generating a sound after the face mask is sufficiently seated on the patient's face, after the drug concentration in the chamber has fallen below a preset threshold, and / or after the patient receives the desired drug dose.

• • •

In a further preferred embodiment of the invention, the device comprises a sprayer, which is preferably a jet sprayer, an ultrasonic sprayer or a pressure grid sprayer.

In another particular embodiment of the invention, the device comprises an aerosol canister for delivering a metered dose of medicament or, in another embodiment, the device comprises an inhaler for inhaling dry powder.

The storage and calculation device is preferably adapted to automatically activate the device when the face mask is sufficiently seated on the patient's face. The storage and computing device preferably comprises a memory for storing data in a lookup table representing a decrease in drug concentration in the chamber over time, and a device for determining drug concentration in the chamber during inhalation according to the data stored in the memory.

In yet another preferred embodiment of the invention, the chamber comprises an inlet to allow gas to be introduced into its interior when air is drawn in from the chamber during inhalation and to reduce drug concentration within the chamber by diluting the gas.

The concentration determining device determines the concentration of drug in the chamber depending on the volume of air inhaled previously by the patient.

The storage and calculation device includes a memory for storing data in a lookup table regarding the reduction of drug concentration in the chamber depending on the volume of inhaled air.

The chamber preferably comprises a first inlet for supplying gas to the chamber and a second inlet in fluid communication with the device.

The invention also provides a device for delivering a medicament to a patient for inhalation according to the invention, the device comprising a nebulizer generating in use an aerosol containing a medicament for inhalation by a patient, a face mask provided with an inhaled air inlet and a storage and calculation device contacting the face mask with the patient's face and calculating the amount of drug inhaled by the patient, the storage and calculation device includes a sensor for measuring the flow of gas drawn by the face mask, the face contacting being determined by monitoring the gas flow through the face mask and the total dose received by the patient is calculated by adding the doses in each inhalation inhalation, the dose of medicament received in each inhalation inhalation is calculated as the volume of drug inhaled in the inhalation volume after compensation corresponding to the dead space volume of the device behind the sprayer.

Preferably, the face mask inlet comprises a one-way valve to prevent exhalation through the inlet. The face mask also includes a gas exhalation outlet provided with a one-way valve to prevent air inhalation through the outlet.

The device according to another preferred embodiment of the invention comprises a display unit for displaying information such as the shape of the inhalation wave, the maximum amplitude of the inhalation wave, the face mask resting on the patient's face, and the dose of medicament received by the patient. In a preferred embodiment, the display unit comprises a light-emitting LCD display or a liquid-crystal LED display.

In another preferred embodiment, the device comprises an acoustic generator for generating sound upon sufficient fit of the face mask on the patient ' s face and / or upon receipt of the desired dose of medicament by the patient.

• · · · · «φ ΦΦΦ ΦΦΦ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ

The storage and calculation device is preferably adapted to automatically activate the nebulizer after a satisfactory fit of the face mask to the patient ' s face.

In another preferred embodiment of the invention, the nebulizer comprises an aerosol generating space comprising an inhalation gas inlet and an outlet for attaching a face mask. A sensor is located upstream of the atomiser, considered in the direction of air flow.

In a preferred embodiment of the invention, the atomiser is a jet atomizer or an ultrasonic atomizer or a pressure grid atomizer.

SUMMARY OF THE INVENTION In a method of securing a face mask to a patient ' s face, the face mask provided with an inhalation gas inlet is tightly applied to the patient's face, the flow of gas sucked in through the face mask is monitored during inhalation by the patient, and the desired face mask position is adjusted until a regular inhalation waveform is achieved.

A substantially regular shape of the inhalation wave is obtained when the peak amplitude over the course of the inhalation wave is substantially at its maximum.

In carrying out the method of the invention, information relating to the face mask abutment in the form of an inhalation wave and the maximum amplitude of the inhalation wave is further shown.

In another preferred embodiment of the invention, an indication of a satisfactory fit of the face mask to the patient's face is provided.

In one preferred embodiment of the invention, the indication comprises the displayed information, or the indication is performed by audible signals.

• «♦« • ···

The invention also provides a method of delivering a dose of medicament to a patient during inhalation using the device of the invention, wherein the device comprises a chamber for temporarily storing the medicament prior to inhalation, a drug delivery device, a face mask provided with an inhaler for gas inhalation and a and a computing device for providing a face mask to the patient ' s face and for calculating the total dose of medicament received by the patient, the storage and computing device comprising a sensor for measuring the flow of gas drawn from the chamber and the device for determining the drug concentration in the chamber during inhalation, decreases over time, at least in part, by deposition of the medicament on the inner surfaces of the chamber, with the method providing a connection between the device and the face mask, the face mask being tightly placed on the face of the patient; monitoring the flow of gas drawn from the chamber upon inhalation and adjusting the desired facial mask position until a substantially regular inhalation waveform is obtained, activating the drug delivery device into the chamber, and calculating the total drug dose received by the patient by adding the drug doses received in each inhalation inhalation, calculated as the amount of medicament inhaled from the chamber in the volume of each inhalation, while compensating for the volume of dead space of the device downstream of the chamber.

In a first preferred embodiment of the method of the invention, a flow connection between the face mask device is provided, the face mask is applied tightly to the patient's face, and the device is activated in the order shown.

In a second preferred embodiment of the invention, a flow connection between the device and the face mask is provided, the device is activated and the face mask is applied tightly to the patient's face, respectively.

In a third preferred embodiment of the method according to the invention, it is

The face mask is placed close to the patient's face, a flow connection between the device and the face mask is ensured, and the device is activated in the order shown.

In a fourth preferred embodiment of the method according to the invention, the face mask is applied tightly to the patient's face, the device is activated and a flow connection between the device and the face mask is provided, respectively.

In a fifth preferred embodiment of the method of the invention, the device is first activated, then a flow connection between the device and the face mask is provided, and the face mask is applied tightly to the patient's face, respectively.

In a sixth preferred embodiment of the method of the invention, the device is activated, the face mask is applied close to the patient ' s face, and a flow connection between the device and the face mask is provided, respectively.

In one preferred embodiment of the invention, a substantially regular inhalation waveform is obtained when the peaks of the inhalation wave amplitude are maintained substantially at maximum.

In carrying out the method according to a further preferred embodiment of the invention, information relating to the face mask abutment is displayed as an inhalation waveform and inhalation wave amplitude peak values.

The method of the invention further comprises an operation to provide an indication of a satisfactory fit of the face mask on the patient's face. In a particular embodiment of the invention, the indication comprises display information or the indication is performed by an audible signal.

In another preferred embodiment of the method, information is displayed

• fc fcfc • fcfc • • fcfc • • fcfc • • fcfc · • fc fcfc related to the dose of drug received by the patient.

In carrying out the method of the invention, an indication of the patient's receipt of the desired dose of the drug is further provided. This indication contains display information or is indicated by an audible signal.

The method of the invention further comprises a further preferred embodiment in which an indication is provided when the drug concentration in the chamber falls below a predetermined threshold. In one preferred embodiment, the indication comprises display information, or the indication is performed by an audible signal.

The storage and calculation device is preferably adapted to automatically activate the device after a satisfactory fit of the face mask on the patient's face.

Preferably, the storage and calculation device is adapted to automatically activate the device after the drug concentration in the chamber has fallen below a predetermined threshold.

The invention also provides a method of delivering a dose of medicament to a patient during inhalation by means of a device comprising an aerosol-generating aerosol-containing medicament for inhalation by a patient for inhalation, a face mask provided with an inhaled gas inlet, and a storage and computing device the facial mask on the patient ' s face and for calculating the total dose of medicament received by the patient, the storage and calculation device comprises a sensor for measuring the flow of gas drawn by the facial mask, forming the flow connection between the facial mask and the nebulizer; of the patient, the flow of gas drawn through the face mask is monitored until a substantially regular inhalation waveform is achieved, the nebulizer is actuated12

·· * ·· ·· • · · • ♦♦ · ·· • ♦ «· ·· • · ♦ · • · · · · • · ·· • ·

of the aerosol-generating aerosol, and calculating the total dose of medicament received by the patient by adding the doses of medicament received in each inhalation inhalation, the dose of medicament received in each inhalation inhalation is determined as the amount of medicament inhaled in the inhaled air volume. behind the sprayer.

In a first preferred embodiment of the method, the flow connection between the nebulizer and the face mask is established in the following order, the face mask is tightly applied to the patient's face, and the nebulizer is finally actuated.

In a second preferred embodiment of the invention, a flow connection is established between the nebulizer and the face mask, the nebulizer is actuated, and the face mask is then tightly applied to the patient's face.

In a third preferred embodiment of the invention, the face mask is tightly applied to the patient's face, establishing a flow connection between the nebulizer and the face mask and actuating the nebulizer.

In a fourth preferred embodiment of the method of the invention, the face mask is tightly applied to the patient ' s face, the nebulizer is actuated and establishes a flow connection between the nebulizer and the face mask.

In a fifth preferred embodiment of the method of the invention, the nebulizer is actuated, a flow connection is established between the nebulizer and the face mask, and the face mask is tightly applied to the patient's face.

In a sixth preferred embodiment of the method according to the invention, the nebulizer is actuated, the face mask being sealed at 13 ° tf tff · tftf tff · tftf · tfftf · tff · tftfft · tff · tftff · tf the patient's face and a flow connection between the nebulizer and the face mask is formed.

A substantially regular shape of the inhalation wave is obtained when the peaks of the inhalation wave amplitude are kept substantially at maximum.

In another preferred embodiment, the method of the invention comprises an operation in which information relating to a face mask abutment in the form of an inhalation waveform and an inhalation wave amplitude peak value is displayed.

The method of the invention also comprises an operation to provide an indication of a satisfactory fit of the face mask on the patient's face. This indication contains display information, or the indication is performed by an audible signal.

In yet another preferred embodiment of the method of the invention, imaging information regarding the dose of medicament received by the patient is prepared.

In carrying out the method of the invention, an indication is also provided of the condition when the desired dose of drug has been received by the patient. This indication contains display information, or the indication is performed by an audible signal.

Advantageously, the storage and calculation device activates the nebulizer automatically after a satisfactory fit of the face mask has been achieved.

BRIEF DESCRIPTION OF THE DRAWINGS

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a device according to a first exemplary embodiment of the invention; FIG. 2 shows a device according to a second exemplary embodiment of the invention;

φ φφ φφ φ φ

Fig. 3 of the device according to the third exemplary embodiment of the invention, Fig. 4 is a graphical representation of the changes in the concentration of medicament in the dispersion chamber of the device of the example in Fig. 3 in the Fig. 3. Fig. 5 is a graph showing the dilution of the drug in the dispersion chamber of the device of Fig. 3 during inhalation; Fig. 6 of the device according to the fourth exemplary embodiment of the invention; Fig. 9 shows the dilution of the medicament in the dispersion chamber of the device of Fig. 6 during inhalation, Fig. 10 of the device according to the fifth exemplary embodiment of the invention before actuating the powder inhaler, Fig. 11 of the device FIG. 10 after actuation of the powder inhaler; FIG 10 shows the dilution of the medicament in the dispersion chamber of the device of FIG. 10 during inhalation, FIG. 14 of the device according to the sixth embodiment of the invention prior to actuation of the powder inhaler, FIG. 15 of the device Fig. 14 after actuation of the powder inhaler; and Fig. 16 a graphical representation of the patient's breathing pattern.

DETAILED DESCRIPTION OF THE INVENTION

Giant. 1 shows a first exemplary embodiment of a device according to the invention.

The device comprises a nebulizer 1 for generating an aerosol containing medicament. The sprayer 1 comprises a spraying space 3 in which an aerosol cloud is formed and is provided with an inlet 5 to which an inhalation valve 7 is connected, which can only be sucked air from the atmosphere, and an outlet 9 connected to the face mask 11.

99

9

999

9 9

9 9

999 99 • 99 99 99 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 99 99 99 99

In a preferred embodiment, the atomiser 1 is a jet atomizer, an ultrasonic atomizer or a pressure grid atomizer. The nozzle atomizer may consist of two types of atomizers, either an air atomizer or a liquid atomizer. An example of an air jet nebulizer that uses pressurized air from a source to atomize a liquid is described in EP-A-0 627 266. An example of a liquid jet nebulizer forcing liquid through at least one outlet nozzle to form a tiny droplet shower is described in WO-A- 94/07607. Ultrasonic atomizers that atomise liquid by means of ultrasonic waves, which are usually generated by an oscillating piezoelectric element, have a variety of forms and also include atomisers in which the liquid is in direct contact with the piezoelectric element or which are provided with a booster environment, in particular a piezoelectric element and a liquid, or sprayers, in which the piezoelectric element oscillates the grating by which the aerosol is produced. Examples of ultrasonic atomizers are described in US-PS 4,533,082 and US-PS 5,261,601. The atomizers described herein include a housing forming a reservoir storing a quantity of liquid dispensed, the housing having a perforated membrane in contact with the reservoir and an ultrasonic vibrator coupled to the housing. oscillating the diaphragm. Another example of an ultrasonic nebulizer is described in WO-A-97/29851. An exemplary embodiment of a pressure grid sprayer, whether or not containing a piezoelectric element, is described in WO-A-96/13292.

The face mask 11 has an inlet 11a through which air can be inhaled and an outlet 11b through which air can be blown out. Creating an outlet 11b separate from the inlet 11a ensures the reduction of dead space to the inside of the face mask 11, this positioning of the outlet 11b being more advantageous than placing it in the inlet 11a or downstream of the inlet 11a, ♦ ·

• »

Because in such a design the exhaled air can dilute the aerosol located downstream of the inlet 11a and thereby increase the unused reflection space. The face mask 11 is further provided with a resilient face seal 13, which in use adapts to the shape of the patient's face and provides a seal between the face mask 11 and the patient's face. The face seal 13 is a hollow cushion seal which can be filled with air or liquid. The face masks provided with such face seals are currently widely used and do not require the use of headband straps, and the large application pressures that may be required when using lip seal masks to provide tight compression force. Another known face seal is disclosed in WO-A-97/09090. The face mask 11 also includes a nasal septum 15 to break the connection between the nose and the mouth of the patient and provide relatively little unused space within the face mask 11. One such face mask 11 is described in US-PS 4,265,595. The face mask 11 is further provided with an expiratory mask. a valve 17 at the outlet 11b through which air is exhaled and by which air cannot be sucked in.

The inhalation valve 7 and the exhalation valve 17 of the nebulizer 1 as well as the face mask 11 have a low flow resistance design, in particular 2.5 Pa @ 10 l / min, and provide a perfect backflow seal. These valves are commercially available. One of these valves is part of the NEBUCHAMBER inhalation adapter from Astra AB, Sweden.

The device is further provided with a sensor 19 located downstream of the nebulizer 1 for measuring the flow of air drawn from the spray chamber 3, a controller 21 for controlling the operation of the nebulizer 1, a processor 23 for controlling the controller 21 and determining the dose of medicament received by the patient and the display unit. 25 for displaying data,

ΦΦ ···

Φ φ · · · · · · φ φ φ φ φ φ • • • • • • •

ΦΦ ΦΦ among other things, the flow of air drawn in from the spray chamber 3, the shape of the inhalation wave and the dose of medication received by the patient. The display unit 25 is preferably a display

LEDs with LEDs or LCD with liquid crystal display.

The device is further provided with a data interface, such as a serial port, to provide communication with external devices.

In a preferred embodiment, the device is provided with means for informing the patient, in particular by generating audible signals, of the correct fit of the face mask 11 or of the required dose of the medicament delivered.

The sensor 19 in the illustrated embodiment of the device is located at the inlet 5 of the atomiser 1 and may be any pressure sensor, microphone, thermistor or ultrasonic flow sensor having a resolution sufficient to measure small volumes of air inhaled by pediatric patients. The required sensitivity of sensor 19 should generally be +/- 0.25 rpm, with data being collected from 10 ms intervals. In a preferred embodiment, the sensor 19 is a pneumatic recording sensor. The pneumatic recorder is an air flow measuring device comprising an obstruction element in the air flow, in particular a grating having a linear relationship between flow and pressure, and a pressure sensor connected across the tubular section with the grating, where the measured pressure is proportional to the flow pipe section.

If the atomiser 1 consists of an air jet atomizer, the regulator 21 controls the supply of compressed air to the atomiser 1, and if the atomiser 1 is an ultrasonic atomizer, the regulator 21 controls the power supply to the atomiser 1. The regulator 21 is particularly adapted to control operation.

The atomiser 1 to maintain the aerosol cloud in the atomization space 2 at a predetermined concentration throughout the inhalation cycle to allow the atomizer to be maintained at a predetermined concentration throughout the inhalation cycle. thus optimizing dosing and achieving aerosol cloud formation at the onset of inhalation without significant delay. In practice, an aerosol cloud may be formed, responding to the immediate need of the patient, by delivering the aerosol intermittently or continuously, but at a variable rate depending on the inhalation rate. Such control is advantageous for the alternative of actuating the nebulizer 1 only at the beginning of the inhalation, since if the nebulizer 1 were only started at the beginning of the inhalation, then a delay of, for example, about 50 ms between the actuation of the nebulizer would be assumed.

I, and by generating an aerosol even when using, for example, an efficient air jet atomizer. This delay reduces the efficiency of aerosol delivery, especially if the volume of the space between the sprayer outlet 9 and the inlet 11a of the face mask

II is not minimal and contributes significantly to the unused space between the atomiser 1 and the patient.

The processor 23 is connected via an amplifier to the sensor 19 and to the controller 21 and sends an operating signal to the controller 21 depending on the air flow measured by the sensor 19 and the parameters determined by the control program. In this exemplary embodiment, the processor 23 comprises a time base, an analog-to-digital converter for converting the analog signal received from the sensor 19 to a digital signal, a permanent ROM containing a control program and lookup tables and a memory with direct RAM input to store measured values. The processor 23 is also connected to the display unit 25 and to the data interface to provide interconnection with the external devices. It is particularly preferred that the device according to this exemplary embodiment is powered by a battery.

When using this device, a user or a patient who may be the same person enters either the processor 23 into the processor 23 or the value 4 * 3 * Φ í · • 4 · · ·

ΦΦΦ ΦΦ φφ «φ

ΦΦ

Φ Φ Φ

Φ Φ • Φ Φ

ΦΦ the required dose or label the drug to be delivered and for which the dose is stored in the processor 23. The face mask 11 is then placed on the patient ' s face and from this point on the patient begins to breathe through the face mask 11. The patient draws air through the spray chamber 3 during inhalation and exhales through the exhalation valve 17 of the face mask 11. during the inhalation wave on the display unit 25. The inhalation wave displayed is monitored to determine when an effective seal has been reached between the face mask 11 and the patient's face. Sufficient sealing is achieved when a substantially regular inhalation wave is formed, i.e., the maximum amplitude of the inhalation wave is maintained at a substantially maximum level as in region A of the respiratory pattern shown in Fig. 16. FIG. 16 peak amplitudes vary and indicate that the seal of the face mask 11 on the patient's face is not perfect. Area B of the breathing graph contains the part (point C) at which the patient briefly interrupted breathing. In this context, it should be noted that Fig. 16 shows the entire breathing pattern of the patient, while the sensor 19, which is located in the air flow path containing the inhalation valve 7, only monitors the inhalation wave of the breathing pattern. To achieve a satisfactory fit of the face mask 11, certain displacements of the face mask 11 are almost inevitably necessary. Once the face mask 11 has been effectively sealed, the sprayer is actuated.

Even to form an aerosol cloud in the spray chamber 3 having a predetermined concentration and the patient continues to breathe. In a preferred exemplary embodiment of the device, an audio signal is transmitted and a corresponding message appears on the display unit 25 to inform the user that the face mask

II is sufficiently sealed on the patient's face. In another preferred embodiment, the nebulizer 1 is activated automatically upon sufficient abutment of the face mask 13.

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In the patient, an aerosol-containing drug is aspirated from whose space 3 through the face mask 11 into the lungs of the patient. During inhalation, the processor 23 continuously determines the dose delivered to the patient. In this exemplary embodiment, upon delivery of the desired dose of medicament to the patient and displaying a report of this effect on the display unit 25, an audible signal is transmitted so that the patient can remove the face mask 11.

In practice, the processor 23 calculates the amount of drug delivered to the patient at very fast repeating intervals, typically every one hundredth of a second during inhalation. This calculation is made during each inhalation inhalation and is compensated for taking into account the unused space of the device downstream of the nebulizer 1.

For each inhalation breath (n = 1,2,3 ...), the dose (D _n ) taken by the patient is calculated as:

D _n = (V _x + V ₂ + ... + VJ * C, where: ν _χ is the volume inhaled in the first sub-period in the inhalation n after inhalation of the volume corresponding to the volume of the dead unused space of the device downstream of the spray space 3;

V ₂ is the volume inhaled in the second sub-period in the inhalation n after inhalation of the volume corresponding to the dead volume of the device behind the spray area 3 ', ν _χ is the volume inhaled in the i-th sub-period in the inhalation n after inhalation of the volume a space of the device behind the spray space 3; and

C is the drug concentration in the spray area 2 ·

Thus, the total dose D of the drug delivered to the patient is 21

• «* · • · • ··· ·· ·· fl ··· ·· • • ·· • • • • • fl • • • • • • · · • • • o • • • • »· ♦ · ·· ·· ··

the reading value of the dose delivered for each inhalation inhalation after inhalation of the volume corresponding to the dead space of the device downstream of the spray space 3 and may be expressed as follows:

D + D ₂ +. . · + D _n , where D _n may represent incomplete inhalation if the required dose is delivered during inhalation inhalation.

As an approximate value of the total dose of drug delivered to a patient, the following relationship may be indicated when the inhalation waveform is a substantially cyclic waveform:

D = (V _t + V _d ) * C * f * t, where V _t is the total volume of inhalation inhalation,

V _d is the dead space of the device downstream of the spray space 3, f is the frequency of inhalation breaths and _t is the inhalation period.

Giant. 2 shows a device according to the invention in a second exemplary embodiment.

In this example, the device has substantially the same design as the device shown in Fig. 1 except that the face mask 11 includes an inhalation valve 26 at its inlet 11a to prevent exhalation by the inhalation valve 26. The inhalation valve 26 has a similar pattern to the inhalation valve 7. and the exhalation valve 17 is designed to provide particularly low resistance to air passage. In a further preferred embodiment of the device it is possible to omit the inhalation valve 7. The operation of this second device is the same as that of Fig. 1.

Giant. 3 shows a device according to a third exemplary embodiment of the invention.

This device has substantially the same construction as the device of Fig. 1, but further comprises a dispersion chamber 27, generally referred to as the attachment, to which the spray chamber 2 of the dispenser 1 is connected. The dispersion chamber 27 comprises an inlet 29 communicating with the inhalation valve 7 and. a sensor 19, and an output 31 communicating with the face mask input 11a.

The basic function of this device is the same as that of FIG. 1, the operation of the atomiser 2 being controlled so as to maintain a predetermined drug concentration in the dispersion chamber 27.

In the second operating mode, the operation of this device is as follows. The user or patient, which may be the user at the same time, enters the processor 23 with either the desired dose of medicament or the type of medicament for which the processor 23 has stored the appropriate dose. The face mask 11 is then applied to the patient's face, at which point the patient may begin to inhale. The patient draws air from the dispersion chamber 27 during inhalation and inhales through the exhalation valve 17 of the face mask 11. The rate of air flow generated by the patient is displayed along with the shape of the inhalation wave on the display unit 25. This inhalation wave is monitored to determine when achieve an effective seal between the face mask 11 and the patient's face. Corresponding sealing is achieved when a substantially regular inhalation wave occurs as described in the previous section in the explanation of the exemplary device of FIG. 1. Thus, regular inhalation waves are achieved when the amplitude maxima are substantially at the highest level. To achieve a sufficiently tight fit of the face mask 11 on the face, it is almost always necessary to reposition the face mask 11 again.

The abutment 1 is activated and the medicament containing aerosol is formed in the dispersion chamber 27. In a preferred embodiment, an audible signal is generated and an appropriate message appears on the display unit 25 informing the user that the face mask 11 is sufficiently sealed on the patient's face. In another preferred embodiment, the nebulizer 1 is activated automatically when the face mask 11 is tightly seated. When the patient inhales, aerosol is drawn from the dispersion chamber 27 through the outlet 31 and the face mask 11 into his lungs. During inhalation, the processor 23 continuously calculates the dose delivered to the patient. In this exemplary embodiment, upon delivery of the desired dose of medicament to the patient, a corresponding message is displayed on the display unit 25 and an audible signal is transmitted, at which point the patient may remove the face mask 11.

However, the actual dose of drug delivered to a patient is dependent on a number of factors, as described in the next section, and the calculation of the dose administered to the patient is determined as a function of all these factors.

Over time, the drug concentration in the dispersion chamber 27 decreases. This is due both to the deposition of the atomized substance on the inner surfaces of the dispersion chamber 27 by gravitational and electrostatic forces, as well as to the dilution effect caused by air from the atmosphere containing no drug and aspirated into the dispersion chamber 27 every time the patient inhales to replace the inhaled volume.

The concentration of drug in the dispersion chamber 27 is time-dependent, provided there is no dilution. The concentration of drug in the dispersion chamber 27 as a function of time is shown in Figure 4.

• · ·· tu »»

The dilution factor, which is a function of the volume of air previously aspirated by the patient from the dispersion chamber 27, is shown in Figure 5.

In practice, the processor 23 calculates the amount of drug delivered to the patient in a large number of short time intervals, typically lasting one hundredth of a second during inhalation. At each of these counting periods, the concentration of drug within the dispersion chamber 27 is calculated taking into account the settling of drug particles on the inner walls of the dispersion chamber 27 over time, and the dilution effect of air that carries no drug particles at the inlet from the dispersion chamber 27. The permanent ROM of the processor 23 includes a data table indicating the concentration of the drug in the dispersion chamber 27 at any time after the drug is delivered from the dispersion chamber 27, based on the rate of settling of a particular drug. The permanent ROM also contains a data table indicating the drug concentration in the dissipation chamber 27 at any time after introducing a certain volume of air into the dissipation chamber 27. Thereafter, the drug concentration in the dissipation chamber 27 is calculated for each counting period.

In the next calculation of inhalation and the device's operation is calculated the dose of drug delivered. This is performed continuously during each inhalation to compensate for the dead space by the dispersion chamber 27.

For each inhalation collected by the patient, he calculates the inspiration (n = 1,2,3 by integration as:

..), the dose D at ^{D = V} L ^C L ^{+ C} 2 ^V 2 + ··· ^{+ V} i ^C i 'where Vi is the volume inhaled in the first sampled period in inhalation inhalation n after a volume corresponding to the inhalation volumes of dead space in the device flow direction beyond the diffusion chamber 25,

_V2 is the volume inhaled in the second sampled period in inhalation inhalation n after inhaling a volume corresponding to the volume of the dead space of the device downstream of the dispersion chamber 27 is the volume inhaled in the ith sampled period in inhalation inhalation n after inhaling a volume corresponding to the volume of the dead space of the device downstream of the dispersion chamber 27, ^C 1 i ^e the calculated concentration in the first sampled period in inhalation inhalation n after inhaling a volume corresponding to the volume of the dead space of the device downstream of the dispersion chamber 27, ^C 2 ³ and the calculated concentration in the second sampled period in inhalation n after inhaling inspiratory volume corresponding to the dead space volume of the apparatus downstream of the chamber 27, ^{c e} ij calculated concentration in the ith sampled period in inhalation inhalation n after a volume corresponding inhaling volume of the dead space in the device SM flow distance downstream of the dissipation chamber 27.

Thus, the total dose D of the drug delivered to the patient is the sum total of the doses delivered with each previous inhalation of the air volume corresponding to the dead space of the device downstream of the dissipation chamber 27 and can be expressed as follows:

D = D · ^ + D ₂ + ... + Dp / where D _n may represent incomplete inhalation if the required dose is already delivered during inhalation inhalation.

FIG. 6 shows a fourth exemplary embodiment of the device according to the invention.

· · · · · · · · · · · · · · · · · · · · · · · · · · ·

The device comprises a dispersion chamber 41, commonly referred to as an adapter, to which a medicament-containing aerosol cloud is delivered. The dispersion chamber 41 has an inlet 43 to which the supply unit 45 is connected and an outlet 47 to which the face mask 49 is connected.

The feed unit 45 is provided with an inlet 51 for inhaled air in use and an outlet 53 in fluid communication with the inlet 43 of the dispersion chamber 41. The feed unit 45 also includes a spray nozzle 55 which is adapted to receive the valve stem of the aerosol canister 57 The medicament containing aerosol cloud into the dispersion chamber 41. In this exemplary embodiment, the cartridge 57 delivers a metered dose of medicament upon actuation.

The face mask 49 is formed as in the second exemplary embodiment of the device. In particular, the face mask 49 is provided with an inlet 49a, an outlet 49b, a resilient face seal 59, a nasal partition 61, an inhalation valve 63 in an inlet 49a, and an exhalation valve 65 in an outlet 49b.

The device is further provided with a first sensor 67 for measuring the flow of air drawn from the dispersion chamber 41 and a second sensor 69 for monitoring each actuation of the drug delivery container 57 to the dispersion chamber 41. In this example, the first sensor 67 and second sensor 69 form part of the delivery unit 45. The first sensor 67 is positioned upstream of the spray nozzle 45 at the inlet 51 of the feed unit 45 and may be formed, as in the previous examples, by any type of sensor, such as a microphone, thermistor or ultrasonic flow sensor having the resolution necessary to measure small volumes of air inhaled by pediatric patients. In a preferred exemplary embodiment, the first sensor 67 is a pneumatic recording sensor. The second sensor 69 in this example is a microswitch positioned to turn on when the cartridge 57 is activated and the metered dose of medicament is delivered to the dispersion chamber 41. In an alternative exemplary embodiment, the second sensor 69 may be omitted and the first sensor 67 used measures airflow aspirated from the dispersion chamber 41 also detects each activation of the cartridge 57. In another alternative example, the first sensor 67 may be located downstream of the spray nozzle 55.

In this case, the device is also provided with a processor 71 coupled to the first sensor 67 and the second sensor 69 via an amplifier to calculate the dose of medicament received by the patient in accordance with the signals of the first sensor 67 and the second sensor 69 and according to the control program. In this example, the processor 71 comprises a time unit or clock, an analog-to-digital converter for converting the analog signal received from the first sensor 67 into a digital signal, a non-volatile ROM containing a control program and associated tables, and direct RAM memory for storing measured values.

The apparatus is also provided with a display unit 73 in the form of a display connected to a processor 71 for displaying, inter alia, the air flow drawn from the dispersion chamber 41, the shape of the inhalation wave and the dose of medicament administered to the patient. The display unit 73 is preferably also comprised of an LED display or an LCD liquid crystal display.

The device is further provided with a data interface, for example a serial port, which is connected to the processor 71 to provide communication with external devices.

As in the examples described in the previous section, the device is provided with means for informing the patient, in particular by generating audible signals about the correct fit of the face mask 49 or the delivery of the desired dose of medicament.

The device also preferably comprises a device for emitting a warning signal when the concentration of medicament in the dispersion chamber 41 falls below a predetermined threshold that would require re-activation of the cartridge 57. In a particularly preferred embodiment, the device comprising the processor 71 is powered from battery .

When using this device, a user or patient, which may be the same person, either enters into the processor 71 the value of the needed dose or indicates the medicament to be delivered and for which the appropriate dose is stored in the processor 71. The face mask 49 is then applied to the patient ' s face and from that moment on the patient begins to breathe through the mask. The patient draws air from the dispersion chamber 41 during inhalation and exhales through the exhalation valve 65 of the face mask 49. The flow of air induced by the inhalation of the patient is displayed along with the inhalation waveform on the display unit 73. The displayed inhalation wave is monitored to determine when an effective seal has been reached between the face mask 49 and the patient's face. Sufficient sealing is achieved if a substantially regular inhalation wave as described in the previous section is made to illustrate the use of the device of Fig. 1, i.e. if the maximum amplitude of the inhalation wave is maintained at a substantially maximum level. To achieve a satisfactory fit of the face mask 49, certain displacements of the face mask 49 are almost inevitably necessary. In a preferred embodiment, to inform the user that the face mask 49 is seating satisfactorily on the patient's face, a beep is emitted and displayed. Once an effective sealing of the face mask 49 is achieved, the reservoir 57 is activated at least once and an aerosol cloud containing the dispersed medicament is released into the dispersion chamber 41. In accordance with conventional practice where the medicament is dispersed in the propellant, the cartridge 57 is shaken prior to actuation to ensure uniform dispersion of the medicament and thereby producing an accurate dose of medicament upon actuation. Inha29 tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf tftf •·· tftflation of the patient with the drug. it sucks from the dispersion chamber 41 through the outlet 47 and enters the face mask 49 and the lungs of the patient. In a preferred embodiment, an audible signal is then generated and an appropriate message is displayed on the display unit 73 when the drug concentration in the dispersion chamber 41 drops below a predetermined value that requires further activation of the cartridge 57. During inhalation the processor 71 continuously determines the dose delivered to the patient's lungs. . In this exemplary embodiment, upon delivery of the desired dose of medicament to the patient, a message is displayed on the display unit 73 and an audible signal is generated, at which point the patient may remove the face mask 49 from the face.

However, the actual dose of drug delivered to a patient is dependent on a number of different factors that will be described in the next section, and the calculation of the dose administered to the patient is determined as a function of all these factors.

Over time, the drug concentration in the dispersion chamber 41 decreases. This is due both to the deposition of the atomized substance on the inner surfaces of the dispersing chamber 41 by gravitational and electrostatic forces, as well as to the dilution effect caused by air from the drug-free atmosphere that sucks into the dispersing chamber 41 every time the patient inhales to replace the inhaled volume.

The concentration of drug in the dispersion chamber 41 is dependent on elapsed time and the number of activations of the cartridge 57, provided that there is no dilution. The concentration of drug in the dispersion chamber 41 is a function of the time and number of activations of the cartridge 57 as shown in FIG. .

The dilution factor, which is a function of the volume of air previously aspirated by the patient from the dispersion chamber 41, is

shown in FIG. 9.

In practice, the processor 71 calculates the amount of drug delivered to the patient in a large number of short time intervals, typically lasting one hundredth of a second during inhalation. In each of these counting periods, the drug concentration within the dispersion chamber 41 is calculated taking into account the settling of the drug particles on the inner walls of the dispersion chamber 41 over time, and the dilution effect of air that carries no drug particles at the inlet from the dispersion chamber 41. Permanent ROM of the processor 71 includes a data lookup table indicating the concentration of drug in the dispersion chamber 41 at any time after introduction of the drug into the dispersion chamber 41, based on the rate of settling of a particular drug. The permanent ROM also contains a data lookup table indicating the concentration of drug in the dispersion chamber 41 at any time after introducing a certain volume of air into the dispersion chamber 41. Thereafter, the drug concentration in the dispersion chamber 41 is calculated for each counted period.

In the next calculation of inhalation and the device's operation is calculated the dose of drug delivered. This is performed continuously during each inhalation to compensate for the dead space by the dispersion chamber 41.

For each inhalation breath (n = 1,2,3 ...), the dose (D) received by the patient is calculated by integration as:

D = ^v i ^c i + ^V 2 ^C 2 ⁺ ··· ^{+ v} i ^c i 'where V ₁ is the volume inhaled in the first count period in the inhalation n after inhalation of the volume corresponding to the dead volume of the device downstream of the dissipation chamber 41 .

V ₂ is the volume inhaled in the second count period in the inhaler 31

by inhaling n after inhaling the volume corresponding to the dead volume of the device downstream of the diffusion chamber 41, the volume inhaled in the i-th count period in the inhalation n after inhaling the volume corresponding to the dead volume of the device downstream of the diffusion chamber 41

Cj is the calculated concentration in the first counted period in the inhalation n after inhalation of the volume corresponding to the dead volume of the device downstream of the dispersion chamber 41,

_C2 is the calculated concentration in the second sampled period in inhalation inhalation n after inhaling a volume corresponding to the volume of the dead space of the device downstream of the chamber 41 ^c ij ^e calculated concentration in the ith sampled period in inhalation inhalation n after inhaling a volume corresponding to the volume of dead space of the device downstream of the dispersion chamber 41.

Thus, the total dose D of the drug delivered to the patient is the sum total of the doses delivered with each previous inhalation of the air volume corresponding to the dead space of the device downstream of the dissipation chamber 41 and can be expressed as follows:

D = + D ₂ + ··· + D _n , where D _n may represent incomplete inhalation if the required dose is already delivered during inhalation inhalation.

Giant. 10 and 11, there is shown a device in a fifth exemplary embodiment. This device is intended for use in conjunction with an inhaler for inhaling a dry powdered medicament.

fl · flfl · flfl · fl flfl ·

The device comprises a dispersion chamber 81, commonly called an adapter, in which a dry drug-containing powder is dispersed. The dispersing chamber 81 is provided with an inlet 83 to which the outlet of the dry powder inhaler 85 is connected, which in use delivers a dry powder containing medicament powder to the dispersing chamber 81, an outlet 87 connected to the face mask 89 and a vent 91. In this exemplary embodiment, the dry powder inhaler 85 is a TURBUHALER inhaler manufactured by Astra AB of Sweden.

The face mask 89 is of the same kind as the masks used in the previous exemplary embodiments. That is, the face mask 89 is provided with an inlet 89a, an outlet 89b, a resilient face seal 93, a nasal partition 94, an inhalation valve 95 at the inlet 89a, and an exhalation valve 97 at the outlet 89b.

The apparatus further includes a sensor 99 disposed downstream prior to entering the dry powder inhaler 85 to measure the flow of air drawn from the dispersion chamber 81 and to detect activation of the dry powder inhaler 85 to deliver the drug to the dispersion chamber 81, a processor 101 coupled to the sensor 99 via an amplifier. calculating a dose of medicament received by the patient in accordance with the signals of the sensor 99 and according to the control program, and a dispersion display unit 103 coupled to the processor 101 for displaying, inter alia, air flow drawn from the diffuser chamber 81 inhalation waveform; The display unit 103 preferably also comprises an LED display with LEDs or a liquid crystal display LCD.

The device is further provided with a data interface, for example a serial port, which is connected to the processor 101 to provide communication with external devices.

φ »φ φ φ φ φ * * φ φ φ φ φ φ φ φ φ φ φ φ φ φ •

ΦΦΦΦΦ φφ φφ φφ φφ

The transducer 99 may be formed, as in the previous examples, by any type of transducer, such as a microphone, thermistor, or ultrasonic flow sensor, having the resolution necessary to measure small volumes of air inhaled by pediatric patients. In a preferred embodiment, the sensor 99 is a pneumatic recording sensor. Alternatively, the sensor 99 may be located downstream of the dry powder inhaler 85.

In this example, the processor 101 includes a time unit or clock, an analog-to-digital converter for converting the analog signal received from the sensor 99 to a digital signal, a non-volatile ROM containing a control program and associated lookup tables, and direct RAM memory to store measured values.

In a preferred exemplary embodiment, the device of the invention comprises, as in the previous examples, means for informing the patient, in particular by generating audible signals about the correct fit of the face mask 89 or the delivery of the desired dose of medicament. The device also preferably includes a device for providing a warning signal when the concentration of medicament in the dispersion dispersion chamber 41 drops below a predetermined threshold that would require re-activation of the dry powder inhaler 85. In a particularly preferred embodiment, the device comprising the processor 101 is battery powered.

When using this device, a user or patient, which may be the same person, either enters into the processor 101 the value of the needed dose or indicates the medicament to be delivered and for which the appropriate dose is stored in the processor 101. The face mask 89 is then placed on the patient ' s face and from that moment on the patient begins to breathe through the mask. During inhalation, the patient sucks air through the dry powder inhaler 85. In the inhaler 85, a dry powder inhaler 85 is used. The airflow induced by the inhalation of the patient is displayed along with the inhalation waveform on the display unit 103. The inhalation wave displayed is monitored to determine when an effective seal has been reached. between the face mask 89 and the patient's face. Sufficient sealing is achieved if the substantially regular inhalation wave as described in the previous section is made to illustrate the use of the device of Figure 1, i.e. if the maximum amplitude of the inhalation wave is maintained at a substantially maximum level. To achieve a satisfactory fit of the face mask 89, certain displacements of the face mask 89 are almost inevitably necessary. In a preferred embodiment, to inform the user that the face mask 89 is seated satisfactorily on the patient's face, a beep is emitted and a message displayed on the display unit 103. Once the face mask 89 is effectively sealed, a dry powder inhaler 85 is prepared and actuated. The inhaler 85 is actuated by moving the piston 92 to the position shown in FIG. 10 and releasing it. In this example, the piston 92 is spring loaded so that when released, it is driven downwardly by the spring pressure of Figure 10 to the position of Figure 11 to produce the desired airflow at the outlet of the inhaler 85 to ensure optimal powder dispersion. in the dispersion chamber 81. When the patient inhales, the medicament is aspirated from the dispersion chamber 81 through the outlet 87 and enters the face mask 89 and into the lungs of the patient. In a preferred embodiment, an audible signal is then generated and an appropriate message is displayed on the display unit 103 if the drug concentration in the dispersion chamber 81 drops below a predetermined value that requires further activation of the inhaler. During inhalation, the processor 101 continuously determines the dose delivered to the patient's lungs. In this exemplary embodiment, upon delivery of the desired dose of medicament to the patient, a message is displayed on the display unit 103, and an audible signal is generated, at which point the signal is generated. the patient may remove the face mask from the face 89.

However, the actual dose of drug delivered to the patient is again dependent on a number of different factors to be described in the next section, and the calculation of the dose administered to the patient is determined as a function of all these factors.

Over time, the drug concentration in the dispersion chamber 81 decreases. This is due both to the deposition of the atomized substance on the interior surfaces of the dispersion chamber 81 by gravitational and electrostatic forces, as well as to the dilution effect caused by no-drug air from the atmosphere which is sucked into the dispersion chamber 81 every time the patient inhales to replace the inhaled volume.

The concentration of drug in the dispersion chamber 81 is dependent on elapsed time, provided there is no dilution. The concentration of drug in the dispersion chamber 81 is a function of time as shown in FIG. 12.

The dilution factor, which is a function of the volume of air previously aspirated by the patient from the dispersion chamber 81, is shown in Figure 13.

In practice, the processor 101 calculates the amount of drug delivered to the patient at very numerous time intervals, typically lasting one hundredth of a second during inhalation. At each of these counting periods, the concentration of drug within the dispersion chamber 81 is calculated taking into account the settling of drug particles on the inner walls of the dispersion chamber 81 over time, and the dilution effect of air that does not carry any drug particles at the inlet to the dispersion chamber 81. The permanent ROM of the processor 101 includes a data lookup table indicating the concentration of drug in the dispersion chamber 83 at any time after the drug is introduced into the dispersion chamber 81, based on the rate of settling of a particular drug. The permanent ROM also contains a data lookup table indicating the concentration of drug in the dispersion chamber 81 at any time after the introduction of a certain volume of air into the dispersion chamber 81. This calculates the drug concentration in the dispersion chamber 81 for each counted period. delivered to the patient. This calculation is performed continuously during each inhalation inhalation and is compensated to take into account the dead space of the device downstream of the dispersion chamber 81.

For each inhalation breath (n = 1,2,3 ...), the dose D received by the patient is calculated by integration as:

D = ν _Λ + V ₂ C ₂ + ... + V _iCi , where ν _χ is the volume inhaled in the first count period in the inhalation n after inhalation of the volume corresponding to the dead volume of the device downstream of the dissipation chamber 81,

V ₂ is the volume inhaled in the second counting period in the inhalation n after inhalation of the volume corresponding to the dead volume of the device downstream of the dissipation chamber 81,

V _x is the volume inhaled in the i-th census period in the inhalation n after inhalation of the volume corresponding to the dead volume of the device downstream of the dissipation chamber 81,

0 _χ is the calculated concentration in the first counted period in the inhalation n after inhalation of the volume corresponding to the dead volume of the device downstream of the dispersion chamber 81, ^C 2 3 ^e calculated concentration in the second counted period in the inhalation n after inhalation of the corresponding dead volume downstream of the dispersion chamber 81, the calculated concentration in the i-th count period in the inhalation inhalation n after inhalation of a volume corresponding to the dead volume of the downstream of the dispersion chamber 81.

Thus, the total dose D of the medicament delivered to the patient is the sum total of the doses delivered with each previous inhalation of the air volume corresponding to the dead space of the device downstream of the dissipation chamber 81 can be expressed as follows:

D = + D ₂ + ·· «+ D _n , where D _n may represent incomplete inhalation if the required dose is already delivered during inhalation inhalation.

14 and 15 show a device in a sixth exemplary embodiment of the invention.

The apparatus has substantially the same construction as the apparatus of the examples shown in Figs. 10 and 11 and differs from these embodiments in that the sensor 99 is mounted at a further inlet 105 into the dispersion chamber 81. The apparatus is also provided with a valve 107 at the next inlet 105, which is normally open to allow inhalation air flow except when the inhaler 85 is actuated. The apparatus further includes a valve 109 at the inlet 83 of the inhaler 85, which is normally closed except when the inhaler 85 is actuated. valve 109 is opened to allow air to be drawn in by the inhaler 85 and to carry dry powder containing the medicament from the interior of the inhaler 85 as it moves. In this example, the valves 107, 109 are electrically operated depending on the actuation of the inhaler 85. The operation of this device is the same as that of the device of Figures 10 and 11.

It is to be understood that the invention is not limited to the illustrated and described exemplary embodiments of the device, but these examples may be modified in many ways without departing from the scope of the invention.

Claims (89)

PATENT CLAIMS An apparatus for securing a face mask to a patient's face, comprising a face mask (11, 49, 89) provided with an inlet (11a, 49a, 89a) through which gas can be sucked in, a sensor (19, 67, 99) ) for measuring the flow of gas drawn in through the inlet (11a, 49a, 89a) of the face mask (11, 49, 89), and an indicator to provide an indication of a sufficient fit of the face mask (11, 49, 89) to the patient's face; 11, 49, 89) is determined by monitoring the flow of gas drawn in through the inlet (11a, 49a, 89a) of the face mask (11, 49, 89) upon inhalation of the patient, and the face mask (11, 49, 89) is considered mounted on the patient's face. if a regular inhalation waveform is achieved. The apparatus of claim 1, further comprising a chamber (27, 41, 81) provided with an outlet (31, 47, 87) in fluid communication with the inlet (11a, 49a, 89a) of the face mask (11, 49, 89). ). Device according to claim 2, characterized in that the chamber (27, 41, 81) is provided with a gas inlet (29, 43, 83). Device according to claims 1 to 3, characterized in that the inlet (11a, 49a, 89a) of the face mask (11, 49, 89) comprises a one-way valve (26, 63, 95) for preventing exhalation through the inlet (11a). 49a, 89a). Device according to claims 1 to 4, characterized in that the face mask (11, 49, 89) is provided with a gas outlet (11b, 49b, 89b). · 9 9 9 9 9 * * * * * t t t t t t t t t t t t t t t t t t ···· · · · · ··· tftf ·· ·· ·· · » Device according to claim 5, characterized in that the outlet (11b, 49b, 89b) of the face mask (11, 49, 89) comprises a one-way valve (17, 65, 97) for preventing inhalation through the outlet (11b, 49b, 89b). . Device according to claims 1 to 6, characterized in that the indicator comprises a display unit (26, 73, 103) for displaying information on the contact of the face mask (11, 49, 89) with the patient's face. Device according to claim 7, characterized in that the display unit (25, 73, 103) comprises an LCD display with LEDs or a liquid crystal LED display. Apparatus according to claims 1 to 8, characterized in that the indicator is an acoustic generator for generating sound after the face mask (11, 49, 89) has been properly seated on the patient's face. A device for delivering a medicament to a patient for inhalation, comprising a chamber (27, 41, 81) for temporarily storing the medicament prior to inhalation, a device (1, 57, 85) for supplying the medicament to the chamber (27, 41, 81). ), a face mask (11, 49, 89) comprising a gas inhalation inlet (11a, 49a, 89a), a storage and computing device to ensure that the face mask (11, 49, 89) is seated on the patient's face and to calculate the dose of medicament received by the patient , the storage and computing device comprises a sensor (19, 67, 99) for measuring the flow of gas drawn from the chamber (27, 41, 81) and a device for determining the drug concentration in the chamber (27, 41, 81) during each inhalation inhalation, concentration of the medicament decreases over time, at least in part due to the deposition of the medicament on the inner walls of the chamber (27, 41, 81), where the abutment of the face mask (11, 49, 89) is determined by monitoring the flow of gas drawn in oz of the chamber (27, 41, 81) and the total drug dose received by the patient is calculated as the sum of the drug doses received at each inhalation inhalation, the drug dose received at each inhalation is calculated as the amount of drug inhaled from the chamber (27, 41, 81) inhalation after compensating for the device's dead space volume behind the chamber (27, 41, 81). Device according to claim 10, characterized in that the inlet (11a, 49a, 89a) of the face mask (11, 49, 89) comprises a one-way valve (26, 63, 95) to prevent exhalation through the inlet (11a, 49a, 89a). ). Device according to claim 10 or 11, characterized in that the face mask (11, 49, 89) is provided with a gas outlet (11b, 49b, 89b). Device according to claim 12, characterized in that the outlet (11b, 49b, 89b) of the face mask (11, 49, 89) comprises a one-way valve (17, 65, 97) for preventing inhalation through the outlet (11b, 49b, 89b). ). Apparatus according to claims 10 to 13, characterized in that the storage and calculation device comprises a sensor (67, 69, 99) for detecting the supply of medicament to the chamber (41, 81). Apparatus according to claim 14, characterized in that the sensor (67, 99) for measuring the flow of gas drawn from the chamber (41, 81) and the sensor (67, 99) for detecting drug delivery to the chamber (41, 81) are consist of the same sensors. Apparatus according to claim 14, characterized in that the sensor (67) for measuring the flow of gas drawn in from the chamber (41) and the sensor (69) for detecting drug delivery to the chamber (41) are separate sensors. Device according to claims 10 to 16, characterized in that the sensor (19, 67, 99) for measuring the flow of gas drawn from the chamber (27, 41, 81) is located upstream of the device (1, 57, 85). . The apparatus of claims 10 to 17, further comprising a display unit (25, 73, 103) for displaying information about the course of the inhalation wave, the maximum amplitude in the shape of the inhalation wave, the face mask (11, 49), 89) on the patient's face, the drug concentration in the chamber (27, 41, 81), a warning signal when the drug concentration in the chamber (27, 41, 81) falls below a predetermined threshold, and the dose of drug received by the patient. Device according to claim 18, characterized in that the display unit (25, 73, 103) comprises an illuminated LCD display or a liquid crystal LED display. The apparatus of claims 10 to 19, further comprising an acoustic generator for generating sound after the face mask (11, 49, 89) is sufficiently seated on the patient's face after the drug concentration in the chamber (27, 41, 81) has decreased. below a preset threshold and / or upon receipt of a desired dose of drug by the patient. Apparatus according to claims 10 to 20, characterized in that the device (1) is a sprayer. 22. The apparatus of claim 21, wherein the atomiser is a jet atomizer. 23. The apparatus of claim 21, wherein the nebulizer is an ultrasonic nebulizer. 24. The apparatus of claim 21, wherein the atomiser is a pressure grid sprayer. Apparatus according to claims 10 to 20, characterized in that the device (57) comprises an aerosol pressure reservoir for delivering a metered dose of medicament. Device according to claims 10 to 20, characterized in that the device (85) comprises a dry powder inhaler. Device according to claims 10 to 26, characterized in that the storage and calculation device is adapted to automatically activate the device (1, 57, 85) after the face mask (11, 49, 89) has been sufficiently seated on the patient's face. Device according to claims 10 to 27, characterized in that the storage and calculation device comprises a memory for storing data in a lookup table representing a decrease in the concentration of medicament in the chamber (27, 41, 81) over time, and a device determining the concentration of medicament in chamber (27, 41, 81) during inhalation according to data stored in the memory. Apparatus according to claims 10 to 28, characterized in that the chamber (27, 41, 81) comprises an inlet (29, 43, 83) for allowing gas to be introduced into its interior space when air is drawn from the chamber (27, 41). 81) by inhalation and reducing drug concentration within the chamber (27, 41, 81) by diluting the gas. The device of claim 29, wherein the concentration determining device determines the concentration of medicament in the chamber (27, 41, 81) as a function of the volume of air inhaled previously by the patient. Device according to claim 30, characterized in that the storage and calculation device comprises a memory for storing data in a lookup table relating to reducing the concentration of medicament in the chamber (27, 41, 81) as a function of the volume of inhaled air. Device according to claims 29 to 31, characterized in that the chamber (27, 41) comprises a first inlet (29, 105) for supplying gas to the chamber (27, 41) and a second inlet (83) in fluid communication with the device (27). 1, 85). A device for delivering a medicament to a patient for inhalation, comprising a nebulizer (1) generating in use an aerosol comprising a medicament for inhalation by a patient, a face mask (11) having an inlet (11a) for inhaled air supply and a storage and calculation device to ensure that the face mask (11) abuts the patient's face and calculates the amount of medicament inhaled by the patient, the storage and calculation device comprises a sensor (19) for measuring the flow of gas drawn by the face mask (11); the face mask (11) and the total dose of drug received by the patient is calculated by adding up the doses of drug received in each inhalation inspiration, the dose of drug received in each inhalation inspiration is calculated as the volume of drug inhaled in the inspiratory volume control after sprayer (1). Apparatus according to claim 33, characterized in that the inlet (11a) of the face mask (11) comprises a one-way valve (26) to prevent exhalation through the inlet (11a). * · · ··· * 9 · · ··· 9 · flfl 9 9 9 · -45- ............. • flfl ···· fl · ····· «« flfl flfl ·· Device according to claim 33 or 34, characterized in that the face mask (11) comprises a gas outlet (11b). 36. The apparatus of claim 35, Ref. characterized in that the outlet (11b) of the face mask (11) comprises a one-way valve (17) to prevent air inhalation through the outlet (11b). Device according to claims 33 to 36, characterized in that it comprises a display unit (25) for displaying information such as inhalation waveform, maximum inhalation wave amplitude, contact of the face mask (11) with the patient's face and dose of medicament received by the patient. Device according to claim 37, characterized in that the display unit (25) comprises an illuminated LCD display or a liquid crystal LED display. Apparatus according to claims 33 to 38, further comprising an acoustic generator for generating sound after the face mask (11) is sufficiently seated on the patient's face and / or upon receiving the desired dose of medicament by the patient. Apparatus according to claims 33 to 39, characterized in that the storage and calculation device is adapted to automatically activate the atomiser (1) after a satisfactory fit of the face mask (11) to the patient's face. Apparatus according to claims 33 to 40, characterized in that the atomiser (1) comprises an aerosol-generating atomization space (3), comprising an inhaler (5) for inhaling gas and an outlet (9) for attaching a face mask. φφ φφ * Φφ φφφ «φφφ ΦΦΦΦ · ΦΦΦΦ φ φφ Φ (11). Device according to claims 33 to 41, characterized in that a sensor (19) is arranged upstream of the atomiser (1) in the direction of the air flow. Apparatus according to claims 33 to 42, characterized in that the atomiser (1) is a jet atomizer. Apparatus according to claims 33 to 42, characterized in that the atomiser (1) is an ultrasonic atomizer. Apparatus according to claims 33 to 42, characterized in that the atomiser (1) is a pressure grid sprayer. 46. A method of securing a face mask to a patient &apos; s face, characterized in that a face mask (11, 49, 89) having an inhaler (11a, 49a, 89a) is in close contact with the face of the patient, monitoring gas flow aspirated through the inlet (11a, 49a, 89a) of the face mask (11, 49, 89) upon inhalation by the patient, and adjusting the necessary position of the face mask (11, 49, 89) until a regular inhalation waveform is achieved. 47. The method of claim 46, wherein a substantially regular inhalation waveform is achieved when the peak amplitude over the course of the inhalation wave is substantially at its maximum. The method of claim 46 or 47, further comprising displaying information relating to the abutment of the face mask (11, 49, 89) in the form of an inhalation wave and a maximum inhalation wave amplitude. Method according to claims 46 to 48, characterized in that an indication of a satisfactory fit of the face mask (11, 49, 89) to the patient's face is provided. 50. The method of claim 49, wherein the indication comprises displayed information. 51. The method of claim 49, wherein the indication is performed by audible signals. A method of delivering a dose of medicament to a patient during inhalation by means of a device, characterized in that the device comprises a chamber (27, 41, 81) for temporarily storing the medicament before inhalation, a device (1, 57, 85) for delivering the medicament to the chamber (27). , 41, 81), a face mask (11, 49, 89) provided with an inlet (11a, 49a, 89a) for inhaling gas, and a storage and computing device for ensuring that the face mask (11, 49, 89) abuts the patient's face and calculates the total dose of medicament received by the patient, wherein the storage and calculation device comprises a sensor (19, 67, 99) for measuring the flow of gas drawn from the chamber (27, 41, 81) and a device for determining the drug concentration in the chamber (27, 41, 81) during inhalation, wherein the concentration of the medicament decreases over time, at least in part, by deposition of the medicament on the inner surfaces of the chamber (27, 41, 81), the method providing a connection between the device (1, 5) 7, 85) and a face mask (11, 49, 89), the face mask (11, 49, 89) is tightly placed on the patient's face, the gas flow drawn from the chamber (27, 41, 81) is monitored during inhalation and adjusted the necessary position of the face mask (11, 49, 89) until a substantially regular inhalation waveform is achieved, the drug delivery device (1, 57, 85) is activated and the total dose of drug is calculated received by the patient by adding up the doses of the drug receives48 0 * 0 0 0 0 0 00 00 »0 0 0 0 0 * 0 0 0 • 000 0 0 0 00 0 0 0 0 0 0 0 0 00 • 0 00 00 00 0 in each inhalation inhalation, calculated as the amount of medicament inhaled from the chamber (27, 41, 81) in the volume of each inhalation, while compensating for the device's dead space volume downstream of the chamber (27, 41, 81). Method according to claim 52, characterized in that a flow connection between the device (1, 57, 85) and the face mask (11, 49, 89)) is provided, the face mask (11, 49, 89) being applied tightly to the the patient's face and activates the device (1,57,85), respectively. Method according to claim 52, characterized in that a flow connection between the device (1, 57, 85) and the face mask (11, 49, 89) is provided, the device (1, 57, 85) and the face mask being activated. (11, 49, 89) is placed close to the patient's face, respectively. Method according to claim 52, characterized in that the face mask (11, 49, 89) is applied tightly to the patient's face, providing a flow connection between the device (1, 57, 85) and the face mask (11, 49, 89). ) and the device (1, 57, 85) is activated in that order. Method according to claim 52, characterized in that the face mask (11, 49, 89) is applied tightly to the patient's face, the device (1, 57, 85) is activated and a flow connection between the device (1, 57) is provided. 85) and a face mask (11, 49, 89) respectively. Method according to claim 52, characterized in that the device (1, 57, 85) is activated, providing a flow connection between the device (1, 57, 85) and the face mask (11, 49, 89) and the face mask (1). 11, 49, 89) is placed close to the patient's face, respectively. ♦ · 4 4 94 9 4 4 4 9 · 9 9 4 4 45 9 9 9 4 9 4 4 4 4 9 9 9 9 · • · · · · · · · · · · Method according to claim 52, characterized in that the device (1, 57, 85) is activated, the face mask (11, 49, 89) is applied tightly to the patient's face and a flow connection between the device (1, 57) is ensured. 85) and a face mask (11, 49, 89) respectively. 59. The method of claims 52-58, wherein a substantially regular inhalation waveform is achieved when the peaks of the inhalation wave amplitude are maintained substantially at maximum. Method according to claims 52 to 59, characterized in that information relating to the abutment of the face mask (11, 49, 89) is displayed as an inhalation waveform and inhalation wave amplitude peak values. Method according to claims 52 to 60, characterized in that an indication of a satisfactory fit of the face mask (11, 49, 89) to the patient's face is provided. 62. The method of claim 61, wherein the indication comprises display information. 63. The method of claim 61, wherein the indication is performed by an audible signal. 64. The method of claims 52-63, wherein information about the dose of medicament received by the patient is displayed. 65. The method of claims 52 to 64, wherein the patient is receiving an indication of the desired dose of the drug. • Φ φ φ φ * φ φ φ φ φ φ 66. The method of claim 65, wherein the indication comprises display information. 67. The method of claim 65, wherein the indication is performed by an audible signal. A method according to claims 52 to 67, characterized in that an indication is provided when the drug concentration in the chamber (27, 41, 81) falls below a predetermined threshold. 69. The method of claim 68, wherein the indication comprises imaging information. 70. The method of claim 68, wherein the indication is performed by an audible signal. A method according to claims 52 to 70, characterized in that the storage and calculation device is adapted to automatically activate the device (1, 57, 85) upon a satisfactory fit of the face mask (11, 49, 89) on the patient's face. Method according to claims 52 to 71, characterized in that the storage and calculation device is adapted to automatically activate the device (1, 57, 85) after the drug concentration in the chamber (27, 41, 81) drops below a predetermined threshold value. 73. A method of delivering a dose of medicament to a patient during inhalation by means of the device, wherein the device comprises a nebulizer (1) generating in use an aerosol containing medicament for inhalation by the patient, a face mask (11, 49, 89) provided with an inlet (11a). of inhaled gas and a storage and calculation device for securing the face mask (11) to the patient &apos; s face and for withdrawing the face mask (11) and fcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcfcf The number of the total dose of medicament received by the patient, the storage and calculation device comprises a sensor (19) for measuring the flow of gas drawn by the face mask (11), the method of establishes a flow connection between the face mask (11) and the nebulizer (1), the face mask (11) is tightly applied to the patient's face, the flow of aspirated gas is monitored using an oil mask (11), until a substantially regular inhalation waveform is achieved, the nebulizer (1) is actuated to form an aerosol containing the medicament, and the total dose of medicament received by the patient is calculated by adding the medicament doses received in each inhalation breath. each inhalation inhalation is determined as the amount of drug inhaled in the volume of inhaled air, compensated for the volume of unused dead space of the device behind the nebulizer (1). A method according to claim 73, characterized in that in the following order a flow connection is established between the nebulizer (1) and the face mask (11), the face mask (11) is tightly applied to the patient's face and the nebulizer (1) finally into action. Method according to claim 73, characterized in that in the following order a flow connection is established between the nebulizer (1) and the face mask (11), the nebulizer (1) is actuated and the face mask (11) is tightly applied to the face patient. 76. The method of claim 73, wherein, in the following order, the face mask (11) is tightly applied to the patient &apos; s face, establishing a flow connection between the nebulizer (1) and the face mask (11) and the nebulizer (1) being introduced. into action. A method according to claim 73, characterized in that, in the following order, the face mask (11) is tightly applied to the patient's face, the nebulizer (1) is actuated and establishes a flow connection between the nebulizer (1) and the face mask (11). Method according to claim 73, characterized in that the sprayer (1) is actuated in the following order, a flow connection is established between the sprayer (1) and the face mask (11) and the face mask (11) is tightly applied to the face patient. Method according to claim 73, characterized in that, in the following order, the nebulizer (1) is actuated, the face mask (11) is tightly applied to the patient's face and a flow connection is established between the nebulizer (1) and the face mask (11). ). 80. The method of claims 73 to 79, wherein a substantially regular inhalation waveform is obtained when the peaks of the inhalation wave amplitude are maintained substantially at maximum. A method according to claims 73 to 80, characterized in that information relating to the abutment of the face mask (11) in the form of an inhalation waveform and an inhalation wave amplitude peak value is displayed. Method according to claims 73 to 81, characterized in that an indication of a satisfactory fit of the face mask (11) to the patient's face is provided. 83. The method of claim 82, wherein the indication comprises imaging information. Tftff tftff tfftff tfftff tfftff tfftff tfftff tf ············ · ••• tf tftf · <tftf tf · 84. The method of claim 82, wherein the indication is performed by an audible signal. 85. The method of claims 73 to 84, wherein imaging information regarding the dose of medicament received by the patient is provided. 86. The method of claims 73 to 85, wherein an indication is provided to indicate when the desired dose of drug has been received by the patient. 87. The method of claim 86, wherein the indication comprises display information. 88. The method of claim 86, wherein the indication is performed by an audible signal. Method according to Claims 73 to 88, characterized in that the dispenser (1) is activated automatically by the storage and calculation device after a satisfactory fit of the face mask (11) has been achieved.