NEBULIZER FOR INFANTS AND RESPIRATORY COMPROMISED PATIENTS

Abstract

An inhaler for dispensing a pharmaceutical to infants and respiratory compromised patients is disclosed.

Claims

1. An inhaler for delivering a pharmaceutical to the airway of a human or animal patient, comprising: a housing containing: at least one dose of a pharmaceutical in powder form; a pressure sensor, temperature sensor, microphone, or other sensor with an output proportional to flow rate; a vibrating device; and an aerosol chamber; and an interface for delivering the pharmaceutical to the patient, wherein the interface is connected to the aerosol chamber of the housing.

2. The inhaler of claim 1, wherein the interface is a facemask.

3. The inhaler of claim 1, wherein the interface is a nasal cannula.

4. The inhaler of claim 1, further comprising a second housing containing the electronics monitoring the pressure sensor and controlling the operation of the vibrating device.

5. The inhaler of claim 1, wherein the vibrating device is controlled to operate for a short duration comprising a fraction of the duration of the breath of a patient.

6. A method for automating the delivery of a pharmaceutical to the airway of a patient, comprising the steps of: providing a pharmaceutical delivery device having a vibrating device, at least one dose of a pharmaceutical, a pressure sensor, temperature sensor, microphone, or other sensor with an output proportional to flow rate, and an aerosol chamber; connecting the pharmaceutical delivery device to an interface through which the patient is inhaling; measuring the breathing pattern of the patient using the pressure sensor, temperature sensor, microphone, or other sensor with an output proportional to flow rate, including the duration of a typical breath of the patient; releasing a dose of the pharmaceutical into the aerosol chamber; sensing the beginning of an individual breath of the patient; and upon sensing the beginning of the individual breath of the patient, operating the vibrating device to deaggregate the pharmaceutical, thereby dispending the deaggregated pharmaceutical into the interface via a synthetic jet, wherein the vibrating device is controlled to operate for a short duration, and wherein the short duration is measured as a fraction of the duration of a typical breath of the patient.

7. The method of claim 6, wherein the short duration is less than or equal to 100 milliseconds.

8. The method of claim 6, wherein the short duration is less than or equal to 25% of the duration of the breath of the patient.

9. The method of claim 6, wherein the steps of sensing the beginning of an individual breath and operating the vibrating device are repeated as necessary over a series of breaths.

10. A method for automating the delivery of a pharmaceutical to the airway of a patient, comprising the steps of: providing a pharmaceutical delivery device having a vibrating device, at least one dose of a pharmaceutical, a pressure sensor, temperature sensor, microphone, or other sensor with an output proportional to flow rate, and an aerosol chamber; connecting the pharmaceutical delivery device to an interface through which the patient is inhaling; releasing a dose of the pharmaceutical into the aerosol chamber; and operating the vibrating device to deaggregate the pharmaceutical, thereby dispensing the deaggregated pharmaceutical into the interface via a synthetic jet, wherein the vibrating device is controlled to operate for a short duration.

11. The method of claim 10, wherein the short duration is less than or equal to 100 milliseconds.

12. The method of claim 10, wherein the short duration is less than or equal to 25% of the duration of the breath of the patient.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Features and advantages of the present invention will be seen from the following detailed description, taken into conjunction with the accompanying drawings, wherein:

[0012] FIG. 1 is a drawing of a pharmaceutical delivery device according to one example described herein;

[0013] FIG. 2 is a drawing demonstrating one possible implementation of the device shown in FIG. 1;

[0014] FIGS. 3A, 3B and 3C are drawings of a pharmaceutical delivery device according to another alternative to the example shown in FIG. 1; and

[0015] FIG. 4 is a schematic demonstrating the operation of a pharmaceutical delivery device in accordance with the examples shown in FIGS. 1-3;

[0016] FIGS. 5, 6A and 6B are charts showing an example of the operation of a pharmaceutical delivery device in accordance with the present invention.

[0017] FIG. 7 is a perspective view of a hand-held pediatric nebulizer in accordance with a preferred embodiment of the invention;

[0018] FIG. 8 is a top plan view of the device of FIG. 7;

[0019] FIG. 9 is a bottom plan view showing details of the facemask portion of the device of FIG. 7;

[0020] FIG. 10 is a schematic diagram illustrating generation of nebulized powder medication in accordance with the present invention;

[0021] FIG. 11 is a perspective view illustrating a pharmaceutical package in accordance with a preferred embodiment of the invention; and

[0022] FIG. 12 is a flow diagram illustrating another embodiment of the invention.

DETAILED DESCRIPTION

[0023] Referring to FIGS. 1-5, the present invention in one aspect provides a device and method for automatically delivering a pharmaceutical to the airway of a human or animal patient. The present invention enables the efficient dispensing of a pharmaceutical to a patient that is either unable to use or has substantial difficulty with prior art inhalers such as described elsewhere. Commonly-owned patent, U.S. Pat. No. 7,343,914, incorporated by reference herein, describes mouthpiece adapters suitable for use by children in connection with a typical dry-powder inhaler (DPI). However, other patients, such as infants, frail or pulmonary compromised adults, and most animals, are still unable to use or have difficulty using such inhalers.

[0024] The present invention therefore provides an inhaler that may be paired with a mask or other breathing apparatus and operated to ensure substantial inhalation of a dose of a pharmaceutical. The inhaler 101 includes an electronics housing 110 for containing the battery and other electronics associated with the control of the device. The inhaler also includes a delivery housing 120, which contains the vibrating device 125, aerosol chamber 121, and at least one dose 105 of a pharmaceutical. The housing is connected to an interface, such as a facemask 141 or nasal cannula 142, or other breathing apparatus known in the art. The device is arranged so that upon operation of the vibrating device, e.g., a piezoelectric device, the dose 105 is expelled from the aerosol chamber 121 into the interface for inhalation by the patient 130, via a synthetic jet (as described above and in our afore-mentioned applications, including U.S. application Ser. No. 12/828,133 and U.S. Provisional Application Ser. No. 61/222,418, which arc incorporated herein by reference). The inhaler also includes a pressure sensor 117, and/or a temperature sensor 118, (or other sensor) to measure the patient's breathing. The sensor(s) may be located within the housing, or alternatively, as part of the interface.

[0025] Because the present invention is intended to be used by a patient unable to use or use with difficulty a currently-available inhaler, it is necessary to devise a different operational scheme to ensure that the patient is able to inhale a substantial amount of the dose, even with tidal breathing.

[0026] As shown in FIG. 4, at step 201 the pressure and/or temperature sensors are used to sense the breathing pattern 210 of the patient. This signal is processed at step 202 to determine the trigger point 211 and the dosing duration 212. (See FIG. 12). At step 203, these parameters are then sent to the electronics to control the dispensing of the dose and the operation of the vibrating device. Finally, at step 204, the dose is placed in the aerosol chamber and the vibrating device is operated according to the established parameters, which may include operating the device over a series of breaths in order to completely deliver the dose.

[0027] FIG. 5 shows the operational parameters in connection with a single breath of a patient. Because the patient's breathing could be labored or at a resting pattern, resulting in low inspiratory flow rates and volumes the dosing duration 212 should be much shorter that the dosing duration used in currently available inhalers. By way of example, the dosing duration may be calculated to be efficient at approximately 25% of the duration of the breath, or roughly one half of the duration of a typical inhaler. Shorter durations may be necessary. In one embodiment, the short duration may be less than or equal to 100 milliseconds.

[0028] Further, as shown in FIGS. 6A and 6B, the inhaler may need to be operated over a series of breaths to fully dispense the pharmaceutical and ensure that the patient has inhaled a substantial amount of the dose. Alternatively, the inhaler may be operated intermittently over a series of breaths which may be timed to coincide with the patient's inhalation, or independent of the patient's inhalation. The number of breaths and the dosing duration may be determined according to the breathing pattern of the patient.

[0029] Turning now to FIGS. 7-12 of the drawings, there is illustrated a dry powder pediatric nebulizer in accordance with a preferred embodiment of the present invention. The nebulizer 310 comprises a housing or body 312 sized and shaped to fit comfortably within the hand of a human adult. Body 312 houses a dry powder aerosol engine, battery power and controls all as will be discussed below. Referring in particular to FIGS. 8 and 9, the hand held nebulizer 310 is connected at its outlet 314 to a facemask 316. Facemask 316 is sized and shaped to fit over the mouth and nose of a patient, and is formed of a resiliently deformable material such as silicon rubber. Facemask 316 may comprise a single wall construction or, if desired may comprise a soft partially air-filled cuff 318 at its distal end, and optionally may include a one-way filter valve 319 to allow the patient's exhale breath to escape. Facemask 316 is friction fitted to the outlet end of nebulizer device 312 so that it may be removed for cleaning and/or disposal and a fresh facemask placed thereon. Also, if desired, facemask 316 may come in different sizes, e.g. for adults, children and infants. The face mask may incorporate a pressure sensor 317 to measure the quality of fit and seal over the patient or the sensor may be incorporated into the inhaler housing. A good seal is preferred to ensure high efficiency of delivery of the drug to the patient and to protect the care-giver from exposure to the drug and the patient from exposure of the drug to the eyes.

[0030] Referring also to FIGS. 9-11 body 312 includes a movable panel 320 for permitting one or more molded bodies or blister packs 322 containing a powdered medication to be introduced into a chamber 323 (shown in phantom) defined within the interior of body 312. Blister pack 322 is guided by guides 324 to locate in contact with the top surface of an aerosolization engine in the form of a vibratory element 326. Alternatively, blister packs 322 may be a molded body that is reused over a number of dosings. The body in this case provides a way for introducing the drug into the chamber. Vibratory element 326 preferably comprises a piezo activator or piezo transducer or a mechanical vibrator, an electro-mechanical vibrator or a magnetostrictive element or other vibratory mechanism. Preferred are aerosolization engines and aerosolization chambers such as described in U.S. Pat. Nos. 6,026,809, 6,142,146, 6,152,130, 7,318,434, 7,334,577, 7,343,914 and published U.S. Application Nos. 2005/0172962 and 2008/0202514, the contents of which are incorporated herein by reference.

[0031] Blister pack 322 preferably comprises a domed dry powder drug package made of cold formed or thermal formed film, and includes a conical, semi-spherical, elliptical, pyradidal or similar top part 334 and flat base 328 such as described in U.S. Pat. No. 7,080,644, assigned to the common assignee. Blister pack 322 has at least one drug ejection aperature 332 substantially opposite base 328 and serving primarily for injection of drug particles. Aperatures 332 may be pre-formed integrally with blister pack 322, or formed as puncture holes when the blister pack 322 is inserted into body 312.

[0032] Blister pack 322 carries a supply of a drug substance or substances which preferably are provided as a dry powder. A single component or several drug combinations may be used, or, the drug substance or substances combined with excipients, such as lactose or combinations thereof. Other additives such as pharmaceutically inactive ingredients, de-aggregation agents, etc., also may be added.

[0033] Body 312 carries a battery 325 for powering the vibratory element 326, as well as a microprocessor or electronic controller 327 for controlling operation of the vibratory element 326, sensor signal processing for inhalation and/or exhalation detection, etc. Body 312 also includes a control panel 338 including one or more activation buttons 340, 342, and a display 344. The display 344 may incorporate active dose feedbacks to indicate such things as device readiness, face mask seal integrity, activation of the aerosol engine during inhalation or tidal breathing and dosing complete, such as described in U.S. Published Application No. US-2005-0183725-A1, the contents of which are incorporated herein by reference. Body 312 also includes one or more side walled apertures 345 which permit air to enter chamber (shown in phantom at 323) from the outside.

[0034] Operation of the Nebulizer is as Described Below.

[0035] A caregiver places the facemask over the mouth and nose of the patient. Thereafter, the caregiver presses the start button 340 which activates the vibrating element 326 for a predetermined time, e.g. 1-2 seconds. The vibrating element engages with the base of blister pack 322 whereupon powdered medication is deaggregated and ejected out of blister pack 334 into chamber 323 as a cloud or powder plume 346 where it is then inhaled by the patient.

[0036] The present invention has several advantages over the prior art. For one, the ability to aerosolize dry powders and deliver same in a nebulizer permits much higher dose concentrations than are possible with liquid carried drugs. Thus, administration time for a dose may be significantly reduced over those of a liquid nebulizer. Also, many drugs are insoluble in water and can't be delivered using conventional nebulizers, or are soluble only in organic solvents which create other problems.

[0037] Another feature and advantage of the present invention is that the generation of powder plume is independent of inhalation rate and inhalation timing. Thus, the nebulizer of the present invention is particularly useful in the case of infants and small children, respiratory compromised patients, and unconscious patients. The above described invention provides controlled, reproducible and recordable pulmonary doses from pre-measured blister packs. Alternatively, a plurality of blister packs may be mounted in the body 312 as a cartridge, and advanced, as necessary. Alternatively the dose amount may be controlled by the number and duration of the delivery ‘pulses’, or aerosol activation cycles.

[0038] The invention is susceptible to modification. For example, facemask 316 may be removed, or the nebulizer mounted directly to a pre-existing ventilator/nebulizing system where it may be run continuously or semi-continuously or intermittedly. The nebulizer also may be triggered to turn on and off by sensing tidal breathing of a patient as illustrated in FIGS. 4 and 12, and operate over one or several breaths. Referring again to FIGS. 5, 6A and 6B, the inhalation and/or exhalation cycle is sensed and the aerosol generator is turned on for a short duration followed by an amount of chase air to carry or follow the particles into the patient. A sufficient quantity of chase air is necessary to ensure lung deposition when inhalation volumes are low and inhalation cycles are short. Any sensor or combination of sensors that can be used to measure or identify the difference in properties between an inhalation and exhalation manuever can be used to synchronize and turn the aerosol generator on and off. Example of sensors that may be used to detect the patients inhalation/exhalation are flow sensors, pressure sensors, temperature sensors that measure the temperature difference between the inhaled and exhaled breath, carbon dioxide or nitric oxide or other gas sensors that measure the gas component level difference between inhaled and exhaled breath, and also physical measurement systems such as chest straps to measure the expansion and contraction of the chest cavity, etc., can be employed for this purpose. Still other changes are possible. For example, active visual, audible or tactile feedback to the patient or caregiver indicating the status of the device and of dosing may be provided including, for example, visual or audible devices as taught in U.S. Pat. No. 7,343,914, the contents of which are incorporated herein by reference. Also, if desired, electronic communication may be provided for connecting the device to equipment connected to the patient for controlling or synchronizing the vibratory element. Also, if desired, the dose or amount delivered to a patient may be determined by the counting and controlling number of timed or pulsed activations of the vibratory element. Also animal or cartoon images may be printed on the inside surface 348 of the facemask 316, to make the instrument more friendly to a child patient, or the device feedback systems, e.g. lights and sounds and vibrations may be used for this purpose.

[0039] A feature and advantage of the present invention is that it provides a mechanism to allow delivery of inhalation therapy to patients not currently served by current commercial inhalers.

[0040] Also, while the invention has been described in particular for use with drugs for treating asthma and COPD, the invention also advantageously may be used for delivery of other drugs including, but not limited to, anti-virals to treat viruses including but not limited to RSV, and anti-biotics, anti-fungals and anti-infectives for treating lung infections and other diseases, or drugs for treating lung cancer.

[0041] Still other changes are possible. For example, it is possible to control the amount of drug delivered to the nasal passages as opposed to just the lower respiratory track by controlling particle size. Still other changes are possible.