Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS3812854 A
Publication typeGrant
Publication dateMay 28, 1974
Filing dateOct 20, 1972
Priority dateOct 20, 1972
Publication numberUS 3812854 A, US 3812854A, US-A-3812854, US3812854 A, US3812854A
InventorsR Buckles, M Keller, A Michaels
Original AssigneeR Buckles, M Keller, A Michaels
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Ultrasonic nebulizer
US 3812854 A
Abstract
A device for the ultrasonic nebulization of liquids. Nebulization takes place in a porous solid body the porosity of which determines the size of the liquid particles generated. The device is especially suitable for nebulizing liquid medicaments for inhalation therapy.
Images(1)
Previous page
Next page
Description  (OCR text may contain errors)

ilnited States Patent Michaels et a1.

[ May 28, 1974 Primary Examiner-Richard A. Gaudet Assistant Examiner-Lee S. Cohen Attorney, Agent, or Firm-Thomas E. Ciotti; Edward L. Mandell; Paul L. Sabatine [57] ABSTRACT A device for the ultrasonic nebulization of liquids. Nebulization takes place in a porous solid body the porosity of which determines the size of the liquid particles generated. The device is especially suitable for nebulizing liquid medicaments for inhalation therapy.

8 Claims, 3 Drawing Figures 1 1 ULTRASONIC NEBULIZER [76] lnventors: Alan S. Michaels, 97 Mt. Vernon,

Atherton; Richard G. Buckles, 491

Middle Ct., Menlo Park, both of Calif. 94025; Michael P. Keller, 2272 Latham St., Mountain View, Calif. 94040 [22] Filed: Oct. 20, 1972 [21] App]. No.: 299,194

[52] US. Cl 128/194, 128/D1G. 2, 239/102 [51] Int. Cl A6lm 15/00 [58] Field of Search 128/194, DIG. 2, 172, 173, 128/193, 145.8, 145.6; 259/D1G. 44; 239/102, 4, 338

[56] References Cited UNITED STATES PATENTS 2,658,169 11/1953 Barret 128/172 x 2 1&4

18 HIGH FREQUENCY G EN ERATOR RNTENIENNN RM I $812,854

/l4 [2 HIGH x FREQUENCY GENERATOR x LIQUID I N; IG.I F SUPPLY I? I LIQUID MOMMA l GENERATOR 16 I8 Y SUPPLY 1 ULTRASONM NEBULIZER BACKGROUND OF THE INVENTION 1. Field Of The Invention This invention relates to ultrasonic nebulizers. More particularly, it relates to a device for ultrasonically producing liquid aerosols having controlled particle size. In a preferred embodiment, the invention relates to an improved ultrasonic nebulizer for inhalation therapy.

2. The Prior Art The art is replete with processes which employ aerosols of liquids. Paints, biocides, personal and home care products, gas chromatography and spectroscopy samples, and inhalable drugs are representative of the many materials which are advantageously employed as aerosols. Most commonly, aerosols are generated by drawing the liquid into a high velocity stream of propellant gas. With the growing awareness of the health hazards posed by many of the known propellants, especially the Freon-type gases, other methods of generating aerosols are receiving increased attention.

It is known that aerosols can be generated ultrasonically. A common form of ultrasonic nebulizer achieves atomization by the disintegration of the geyser which is produced in a body of liquid by contacting the liquid with a focused beam of ultrasonic compressed wave energy. Devices of this type have been used, for example, in inhalation therapy (see U.S. Pat. No. 3,561,444 issued Feb. 9, l97l to Boucher or No. 3,387,607 issued June 1 1, 1968 to Gauthier et al.) and in sample atomization (see U.S. Pat. No. 3,325,976 issued June 20, 1967 to West). Another known type of ultrasonic nebulizer achieves atomization by dripping the liquid to be dispersed onto a continuously ultrasonically vibrating solid plate which breaks the liquid into a variety of particles. Such a device is shown in U.S. Pat. No. 3,291,122 issued Dec. 13, 1966 to Engstrom et al.

known that the point at which an aerosol particle deposits in the respiratory system is a function of particle size; micron particles are laid down in the mouth and larynx, 6 to 9 micron particles are preferentially.

deposited in the bronchi, 3 to 6 micron particles are preferentially deposited in the bronchioli, 1 to 3 micron particles are deposited in the alveoli, while particles much smaller than about 1-micron are not retained in the respiratory system by Brownian collision with all walls; most of these particles are exhaled.

Many respiratory diseases affect only one-of the areas of the respiratory system: for example, pneumonia and emphysema affect the alveoli, bronchitis affects the bronchioli, asthma affects the bronchi or bronchioli, etc. Since the drugs used to treat these diseases, for example, epinephrine, norepinephrine, prostaglandins, steroids, antibiotics, detergents and the like are often highly potent and/or systemically toxic, it would be of utmost advantage to minimize drug dosage by delivering the drug precisely to the affected area. More precise particle size control than possible heretofore would help minimize extraneous drug applications.

Another way to reduce drug dosage during inhalation therapy would be to deliver the drug as a precisely timed pulse. It has been found that the flow of gas in and out of the respiratory system has essentially plug flow characteristics with the first gas inspired eventually filling the most distant alveoli, the last gas inspired filling only the larynx, etc. Precise delivery of an accurately determined pulse of atomized drug at an accurately determined point during inspiration, thus would result in further control of the location of drug deposit.

Prior ultrasonic nebulizers are not suitable for accurate Both of these conventional types of nebulizing devices can effectively continuously produce large volumes of crude aerosol but both have three serious disadvantages when preceise nebulization is desired. First, they do not permit accurate control of the amount of liquid atomized; second, they also require relatively long times (often I to 10 seconds) after starting to generate a stable consistent aerosol, and finally, they fail to directly generate an aerosol having uniformly sized particles (so-called monodispersed aerosols).

This last failing is especially serious since it is often necessary or desirable to have a monodispersed aerosol. On a theoretical basis, it has been shown that continuous ultrasonic nebulizers should produce uniform particles related in diameter to the reciprocal of the ultrasonic frequency employed. In practice, however, prior ultrasonic atomizers have produced a variety of extraneous large particles which must be screened, settled or otherwise removed, albeit incompletely, as may be noted in U.S. Pat. No. 3,291,122 and Boucher et al. 26 Annals ofAllergy 591 at FIG. 4 (1968). This inability to control particle size has limited the usefulness of conventional ultrasonic nebulizers especially in inhalation treatment of the respiratory system where precise control of particle size is most advantageous and true monodispersed aerosols have been long desired.

The respiratory system comprises a series of decreasing diameter branched tubes, including the mouth, larynx, trachea, bronchi, bronchioli and alveoli. It is pulsed delivery. These devices often require at least several seconds of tuning to achieve a usable aerosol. When used in pulsed applications, conventional ultrasonic nebulizers rely upon interrupting the transmission of the aerosol by bulky ducts and poorly controllable valves rather than by controlling the aerosols generation.

OBJECTS OF THE INVENTION Accordingly, it is an object of the present invention to provide a new and improved nebulizer of the ultrasonic type.

A further object of this invention is to provide an ultrasonic nebulizer which will permit precise control of the amount of liquid nebulized.

A further object of this invention is to provide an ultrasonic nebulizer which will permit control of the size of liquid particles formed.

Another object of this invention is to provide a device for the production of aerosols which may be used with improved efficiency for inhalation therapy or other therapeutic purposes.

Yet another object of this invention is to provide an ultrasonic nebulizer for inhalation therapy which can be controlled to deliver a medicament-containing aerosol in the form of a pulse of particular particle size and amount of medicament; positioned at a particular point in the inspiration cycle.

STATEMENT OF THE INVENTION It has now been found that the foregoing objects, as well as other objects, advantages, and features which will become apparent from the detailed description to follow, are attained by a nebulizer which includes a porous body having a defined intercommunicating pore structure, an oscillator capable of vibrating the porous body at an ultrasonic frequency and a system for supplying liquid to be nebulized to the pores of the porous body.

BRIEF DESCRIPTION OF THE DRAWINGS In the drawings,,..wherein like reference numerals designate like parts:

FIG. 1 is an essentially diagrammatic cross-sectional view of an embodiment of the ultrasonic nebulizer of the invention;

FIG. 2 is an essentially diagrammatic cross-sectional view of another configuration of a nebulizer of the invention, and

FIG. 3 is a cross-sectional view of yet another configuration of the nebulizer of the invention.

DETAILED DESCRIPTION OF THE INVENTION As illustrated in FIG. 1, an ultrasonic nebulizer l embodying the present invention has a porous solid body 11 having a defined fixed intercommunicating pore structure. Solid body 11 is affixed to ultrasonic horn or antennuator 12 which is in turn attached to a suitable piezoelectric crystal or other electro-mechanical transducer 14. Crystal 14 is connected via cable 16 to high frequency signal generator which produces an ultrasonic signal of adequate power to oscillate crystal 14. The frequency generated by generator 15 is very suitably the resonant frequency of crystal 14 or a harmonic thereof. Cable 16, generator 15, crystal l4 and horn 12 in combination cause porous body 11 to vibrate at an ultrasonic frequency. Liquid to be nebulized is forced under pressure from liquid supply 17 through conduit 18 through concentric channel (or bore) 19 in horn 12 to the interconnected pores of porous body 11 which communicate with channel 19. Conduit 18 is attached to horn 12 in a manner which does not interfere with the ultrasonic oscillation of horn l2 and porous body 11. As will be appreciated by those skilled in the art, the embodiment of the invention illustrated in FIG. 1 is much simplified to clearly set out the invention. Details, such as for example a housing for the nebulizer or the method of flexibly attaching crystal 14 to the hous ing or the exact method of fastening conduit 18 to channel 19, may be supplied by one skilled in the art without departing from the spirit of this invention. Likewise, minor modifications, such as the addition of a capability for cooling crystal 14, may be employed.

In operation, liquid to be nebulized is passed through conduit 18 and channel 19 to porous body 11. The pores of body 11 are intercommunicating, so that liquid can be conducted through solid body 11. Thus the liquid from channel 19 moves to the outer surface of porous body 11 and there is nebulized by the ultrasonic vibration into an aerosol having a particle size distribution which is related to the diameters of the pores of body 11.

In accordance with the present invention, liquids are nebulized to aerosols using an ultrasonically vibrating porous body having a fixed pore structure. Unlike prior ultrasonic nebulizers wherein the size of the particles in the aerosol was determined by the frequency of the ultrasonic vibration, the particle sizes achieved with the instant nebulizers are related to the internal geometry of this porous body. Aerosol particle size is a function Particle diameter 2 X pore diameter For example, when a porous body having uniform 10 micron pores is used in the present invention, the aerosol particles which result are uniformly from about 18 to 22 microns in diameter. When a porous body having uniform 4 mircon diameter external surface pores is substituted an aerosol having particles from about 7 to 9 micron in diameter is formed. This particle size to pore diameter relationship appears to hold over the range of body external pore diameters of from about 0.5 micron to about 50 microns.

When a body having pores of a variety of sizes is employed, a multi-sized aerosol is obtained. In the preferred embodiments of this invention, wherein aerosols for inhalation therapy are produced, it is most often preferred to have uniform particle sizes. Bodies having uniform pore diameters in the range of from 0.5 to 5 microns produce aerosols ideal for many inhalation applications. Most specifically, bodies having all or a major proportion of their pores in the range of from 0.5 to 1.5 microns produce aerosols excellentfor inhalation treatment of the alveoli, bodies having their pores in the range of from 1.5 to 3 microns produce aerosols well suited for treating the bronchioli, while 3 to 5 micron pore bodies produce aerosols most useful for treating the bronchi. As used herein, a body is defined to have a uniform pore diameter within a range when at least about percent of all its pores fall within the given range. Preferably at least about percent of all the pores fit within the specified range.

The pores of the porous body must be joined into an intercommunicating network since when used in accord with this invention, liquid will be passed from one side of the porous body through to the other side.

To achieve reproducible results, the size of the outer pores of the porous body should be fixed. The material of construction of the porous body is not critical so long as it provides a fixed pore size. Porous ceramic oxides may be used as well as porous glasses and metal frits, compressed porous plastics, and certain filters (e.g., nucleopore). These materials are readily available, being used conventionally as filters and catalyst supports.

The porous body should be relatively thin, generally not more than about 1 or 2 cms thick, preferably from 0.01 to 1 cm thick. Undesirably large amounts of energy are required to force the liquid to be nebulized through thicker bodies.

The porous body may be comprised of several layers, for example an internal macroporous layer, which permits the facile passage of liquid, in combination with an outer layer or skin having the required pore size distribution. Such a material can be made by carefully annealing or firing the surface of a macroporous support or by bonding a thin sheet of microporous ceramic, for example 0.005 cm thick, to a sheet of macroporous ceramic, for example 1 cm thick.

The porous body must be vibrated ultrasonically to produce the desired aerosol. This may be carried out by connecting the body to an ultrasonic vibrator such as, for example, by affixing the body to a piezoelectric ceramic crystal. This connection is preferably made through an antennuator horn, which when correctly matched to the piezoelectric crystal frequency, effeciently transmits the ultrasonic oscillation of the piezoelectric crystal to the porous body and if sized correctly permits the ultrasonic energy to be multiplied and focused in the porous body where nebulization occurs. The size and shape of the antennuator horn 12 is not critical. Ideally, it is sized taking into consideration its material and the velocity of ultrasonic waves therethrough to achieve a harmonic relationship at the frequency employed.

The porous body is attached or affixed to the antennuator horn by a method enabling a tight fit and firm attachment to be achieved. The exact method of affixing the porous body to the antennuator horn, while not critical, must be chosen with care. A tight fit must be achieved. Glueing or soldering can be used so long as the pores of the porous body are not blocked or appreciably obstructed. Clamping or threading the porous body to the antennuator horn are acceptable means of attachment.

The antennuator horn is attached to a piezoelectric ceramic crystal or transducer 14. Piezoelectric crystals and their use as transducers are well known. They may be made of materials such as lead zirconate or titanate, and calcium zironate or titanate, with or without traces of salts, for example yttrium, lanthanum, strontium or cobalt. To permit good electrical contact, they generally are coated on two opposite faces with electrically conducting metallic layers. A high frequency signal generator drives the piezoelectric crystal. This generator is capable of producing a signal having a frequency of from l5.00 kilohertz (Khz) to about 100.00 Khz. The power output required depends upon the amount of liquid being nebulized per unit time and the area and porosity of the porous body. As a general rule, at least 20,000 dyne-cm are needed to nebulize 1 cc of liquid into less than 20 micron particles. Best results are obtained when the power output is from about 1 X to about 1 X 10 dyne-cm.

Liquid to be nebulized is supplied to the porous body through channel 19 in antennuator horn 12. Channel 19 is illustrated as coaxial with horn 12. This is not critical. It is essential that channel 19 contact body 11 in a manner that the pores of body lll can communicate with channel 19 and that liquid passing through channel 19 can pass through the pores to the surface of body 11 and there be nebulized. Liquid is fed to channel 19 under pressure via conduit 17 from liquid supply 16. It is required that the liquid be fed under pressure if a substantial feed rate is to be achieved. The pressure employed will depend on the pore size of body 11, the viscosity of the liquid being fed, etc. Generally, pressure of from I to 20 psi are suitable and may be achieved by for example, moving the liquid with pumps, compressed gas cylinders and the like.

A great variety of liquids may be nebulized by an apparatus as illustrated in FIG. 1. Water and aqueous solutions, such as of drugs, herbicides, dilute paints and dyes and the like are suitable, as are non-aqueous liquids and solutions having viscosities not appreciably greater than about 500 centipoises. Viscous liquids, such as heavy oils, generally are not suitable for nebulization with the present apparatus as they tend to clog the porous body. Light organic materials such as lower hydrocarbons, oxyhydrocarbons and liquid halohydrocarbons may be easily nebulized for a variety of uses such as for flame spectrographic analysis and similar scientific investigations. Liquid medicaments, both neat and in aqueous and non-aqueous solutions which meet the above viscosity criteria are very suitably nebulized by the device of this invention.

Medicaments which may be administered to the respiratory tract by the present invention include conventional inhalation therapy substances such as bronchodilator decongestants, for example, epinephrine, isoproterenol, isoetharime and phenylephrine; moistening thinning and detergent solutions such as superinone; mucolytic agents such as acetylcystune and enzymes, for example pancreatic enzyme; and water or saline humidity.

Turning now to FIG. 2, a diagrammatic illustration is given of an embodiment of the nebulizer of this invention adapted for use as an inhaler for inhalation therapy. The principle components of this inhaler inhaler 2) are the same as those of the nebulizer of FIG. 1, including porous body 11, antennuator horn l2, piezoelectric crystal 14, signal generator 15, cable 16 and liquid supply system 17, here shown as a pressure canister; connected to channel 19 via conduit 18. Inhaler 2 also has, in combination with the foregoing components, a mouthpiece 20 adapted at one end to fit the patients mouth and to admit air as well as medicament through its other end as illustrated, as well as means for automatically controlling the nebulizer during the respiration cycle. This automatic control includes an inspiration responsive detector 21, positioned in the airstream of mouthpiece 20, which reacts to changes in the velocity or pressure of the airstream within mouthpiece 20 thus signalling the commencement of inspiration to control 24 via means 22. Control 24 then opens valve 25 via line 26 and admits the desired amount of medicament from supply pressure canister 17, to line 18, channel 19 and porous body 11. Control 24 also turns on, via line 27, high frequency generator 15 which activates piezoelectric crystal 14 which ultrasonically vibrates horn 12 and attached porous body 11 to nebulize precisely the amount of medicament desired. Inhalation detector 21 and controller 24 may be set to deliver medicament throughout the inspiration cycle or in an especially advantageous mode of operation may be set to order a short burst (say from 0.1 to 1 second) of medication ata preset point during inspiration. This point may be based on the length of time from the start of inspiration or more preferably may be based on the volume of gas inspired. The volume may be simply derived by detecting and integrating the inspiration velocity. The nebulizer of this invention can produce a stable cosistant aerosol of uniform particle size essentially instantaneously, for example, within about 2 milliseconds. Thus it is possible to precisely-insert a burst of aerosolized medicament at any desired point in the inspiration cycle and therefore achieve much improved control of inhalation medicament delivery.

Although these constructional details are not illustrated, the inhaler of FIG. 2 can be constructed suitable for stationary or portable use. Because of the excellent direct control of particle size and amount of medicament nebulized, possible with the present invention, bulky filters, classifiers and the like are not required. Also, the electrical power demands of the inhaler of FIG. 2 are modest. Thus it can be constructed, if desired, to be battery operated in a highly portable form.

Turning now to FIG. 3, an embodiment of the invention, atomizer 3, suitable for generating bulk inhalation aerosols or for nebulizing liquid chemical samples for spectrographic or chromatographic analysis is shown. Atomizer 3 is similar to the embodiments of FIGS. 1 and 2 and includes porous body 11, which is here illustrated, not to scale, as a two layer body having a thin (0.05 cm) outer layer having the pore geometry which will give the particle size distribution desired the thicker (0.5 cm) inner layer having a macroporous structure adapted for the facile passage of liquid to be nebulized. Porous body 11 is attached to antennuator horn 12 by means of threaded compression collar 29. Horn 12 is attached to piezoelectric crystal 14 which is driven by ultrasonic oscillations generated by high frequency generator 15 and transmitted via cable 16. Liquid to be nebulized, for example water, is supplied under pressure by liquid supply 17 and line 18 to channel 19 on horn 12. Channel 19 is branched at its upper end where it contacts body 11. This facilitates the more ready passage and even distribution of liquid into body 11. The atomizer is mounted in housing 30, which is essentially sealed except for carrier gas inlet 31 and outlet 32. In operation, carrier gas, which for inhalation uses is usually air or oxygen containing a blend of gasses and for sample atomization is usually a noninterfering gas such as helium or nitrogen, is passed into housing 30 in inlet 31. A mixture of nebulized liquid and carrier gas is then withdrawn via outlet 32 and used as intended by means not shown.

- The following examples are merely illustrative of the present invention and are not to be considered as limiting the scope of the invention in any way.

EXAMPLE I An ultrasonic nebulizer, substantially as shown in FIG. I, is constructed. As porous body 11 is employed a 0.1 cm thick, 0.5 cm diameter disc of porous ceramic (aluminum oxide), having a relatively uniform porosity (some pores are as large as l or 12 microns, some are as small as about 4 microns) and a mean pore diameter of 6 microns. This body is glued on horn 12, care being taken to avoid blocking the pores of body 11. Antennuato'r horn 12 is constructed from brass and has the following dimensions: length, 3.12 inches, large diameter 0.45 inches, small diameter 0.20 inches. Channel 19 is coaxially bored in horn l2 and it has a diameter of 0.025 inches. A 0.50 inch piezoelectric ceramic is used as crystal [4. A Hewlett-Packard signal generator and McIntosh 2 l 00 Amplifier having a power output of 205 watts is employed as generator 15. Channel 19 is connected to a Harvard infusion pump. In operation, a 30.00 kilohertz oscillation of l8.2 watts power is applied to antennuator horn l2 and porous body 11. Water is pumped to porous body 11 at 20 psi pressure. The water nebulizes and is emitted from body 1 1 as an aerosol having particle diameters of from about 8 to about 20 microns corresponding to two times the diameter of the pores of body 11.

EXAMPLE 2 The experiment of Example I is repeated with one modification. As porous body 11 is employed a similarly sized disc of porous ceramic having a mean pore diameter of microns. The aerosol produced in this experiment has an average particle size of about microns.

EXAMPLE 3 The experiment of Example 1 is repeated with one modification. The antennuator horn having an internal bore and a porous ceramic tip is replaced with a solid horn having no ceramic tip. Liquid is fed to the end of the horn via an external 0.040 inch diameter'tube and a Harvard Positive Displacement pump, operated at 10 psi. An ultrasonic frequency varying from 25 KHz to KHz is applied, with energies of from X 10 400 X 10" dyne-cm. Throughout these ranges of frequencies and energies only randomly sized l0 70 micron particles of liquid are formed.

EXAMPLE 4 A series of experiments in accord with the experiment of Example 1 are conducted. In three experiments the liquid flow rate is varied from 0.0817 [Ll/SEC to 0.4l7 (Ll/Sec. The power requirement changes from 29 watts to 18 watts as the liquid feed is decreased. (all at 30 KHz). The particle size of the resulting aerosol remains constant averaging 15 microns.

In three additional experiments the glued porous body is replaced by a body of the same material attached by a threaded brass collar. Because of the resulting change in horn mass a new frequency (28 KHz) is found to be optimum. The aerosol particle sizes are the same as in the first three experiments. The power requirements at similar flow rates are reduced to form 18 to ll watts.

EXAMPLE 5 a. An inhaler substantially in accord with FIG. 2 is constructed. As liquid is employed a solution of medicament comprising epinephrine in distilled water. Controller 24 is set to order nebulization of medicament throughout the inspiration cycle. As porous body 11 is employed a glass frit having a uniform pore diameter of 5 to 6 microns. A patient inhales through mouthpiece 20. This flow of air is noted by detector 2]. Controller 24, responding to the signal of detector 21, then opens valve 25 and energizes high frequency generator 15 which in turn actuates crystal 14 which vibrates horn 12 and porous body 11. The medicament is nebulized into an aerosol having 10 to l2 micron particles which is inspired by the subject. These particles preferentially deposit on the throat and larynx of a patient employing the inhaler.

b. The experiment of part (a) is repeated using a 3 to 5 micron pore size glass frit. An aerosol having 6 to 10 micron particles is formed. This aerosol deposits preferentially in an inhaling patients bronchi.

c. Similarly, when a l to 2 micron frit is used, a 2 to 4 micron aerosol is formed, which deposits preferentially in a patients alveoli.

d. The experiment of part (c) is repeated with one change. Controller 24 is set to deliver only a short pulse of aerosol positioned at the initial portion of the inspiration cycle. In this case, the particles of medicament tiavell to and are primarily deposited in the most distant a V60 1.

EXAMPLE 6 A sample of lower ketones is to be analyzed by flame photometric detector gas chromatograph. An aerosolizer in accord with FIG. 3 is constructed using a bilayer ceramic porous body, the outer layer having an average 9 pore diameter of 2 microns, the inner having a 30 mircon average pore diameter. The mixed ketones are fed to the porous body, a suitable ultrasonic frequency is applied and a suitable carrier gas is fed via inlet 31. An aerosol of ketone is produced by the nebulizer and is carried therefrom by a carrier gas through the chromatograph to a flame photometeric detector where it is analyzed.

We claim as our invention:

1. An ultrasonic nebulizer for atomizing a liquid medicament comprising in combination:

A. a porous solid body having a defined intercommunicating pore structure adapted to receive said liquid medicament, pass said liquid medicament through its pores and discharge said liquid medicament through one of its ends, the diameters of at least 75 percent of the pore openings in said one end being in the range of from 0.5 to 5 microns;

B. means for supplying said liquid medicament to said porous body; and

C. means for vibrating said porous body comprising:

2. The nebulizer according to claim 1 wherein at least 85 percent of said diameters are in said range.

3. The nebulizer according to claim 1 wherein the sizes of said particles are essentially twice the diameters of said pore openings.

4. The nebulizer according to claim 1 wherein the porous body comprises an internal macroporous layer which permits facile passage of said liquid medicament and an outer porous layer whose exterior surface defines said one end.

5. The nebulizer according to claim 1, said nebulizer being adapted to atomize the liquid medicament for inhalation by a patient and including:

D. a mouthpiece for transferring the atomized liquid medicament from said one end of the porous body to the mouth of the patient, one end of which communicates with said one end of the porous body and the other end of which is adapted to be received within the mouth of the patient.

6. An ultrasonic nebulizer for atomizing a liquid according to claim 1 wherein the means for supplying liquid to the pores of the porous solid body comprises means for supplying liquid under pressure to a bore in the antennuator horn, which bore communicates with the pores of the porous solid body.

7. An ultrasonic nebulizer for atomizing a liquid medicament for inhalation by a patient comprising in combination, a cylindrical antennuator horn having a large diameter end and distal therefrom a small diameter end and a passageway extending from the small diameter end coaxially through the horn to an external opening; a porous solid body having external pores of diameter of from 0.5 microns to 5 microns affixed to the small diameter end of the antennuator horn, and having a defined intercommunicating pore structure in communication with the passageway; liquid supply means for supplying the liquid medicament to the external opening of the passageway; vibrating means for vibrating the cylindrical antennuator horn and afiixed porous solid body at a frequency of from about 15 Khz to about Khz; and a mouthpiece one end of which communicates with said external pores and the other end of which is adapted to be received within the mouth of the patient.

8. An ultrasonic nebulizer according to claim 7 including an inspiration responsive detector positioned within the airstream in said mouthpiece and operatively interconnected with said liquid supply means and said vibrating means, said detector being adapted to activate the liquid supply means and vibrating means in response to physical changes it detects within said air stream.

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US2658169 *Mar 14, 1949Nov 3, 1953Centre Nat Rech ScientProduction of aerosols
US2949900 *Jun 2, 1958Aug 23, 1960Albert G BodineSonic liquid sprayer
US3121534 *Sep 29, 1960Feb 18, 1964Exxon Research Engineering CoSupersonic liquid atomizer and electronic oscillator therefor
US3214101 *Mar 31, 1964Oct 26, 1965Little Inc AApparatus for atomizing a liquid
US3243122 *Feb 24, 1965Mar 29, 1966Alvin A SnaperUltrasonic spray apparatus
US3400892 *Dec 2, 1965Sep 10, 1968Battelle Development CorpResonant vibratory apparatus
US3561444 *May 22, 1968Feb 9, 1971Bio Logics IncUltrasonic drug nebulizer
US3653379 *Aug 20, 1970Apr 4, 1972Glenn Joseph GAdjustable pressure ippb ventilator
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US3912168 *Jan 30, 1975Oct 14, 1975Teledyne Ind Inc Teledyne AquaIrrigation lavage
US4106503 *Mar 11, 1977Aug 15, 1978Richard R. RosenthalMetering system for stimulating bronchial spasm
US4109863 *Aug 17, 1977Aug 29, 1978The United States Of America As Represented By The United States Department Of EnergyApparatus for ultrasonic nebulization
US4119096 *Aug 24, 1976Oct 10, 1978Siemens AktiengesellschaftMedical inhalation device for the treatment of diseases of the respiratory tract
US4261512 *Feb 20, 1980Apr 14, 1981Boehringer Ingelheim GmbhInhalation aerosol spray device
US4292973 *Jan 3, 1980Oct 6, 1981Kabushiki Kaisha Kurio-MedikaruApparatus for refrigeration treatment
US4348873 *Jun 23, 1981Sep 14, 1982Kabushiki Kaisha Kurio-MedikaruApparatus for refrigeration treatment
US4412538 *Jul 31, 1981Nov 1, 1983Kabushiki Kaisha Kurio-MedikaruApparatus for refrigeration treatment
US4541966 *Aug 24, 1984Sep 17, 1985Penlon LimitedGas humidifying apparatus and method
US4546768 *Dec 14, 1982Oct 15, 1985Feierabend GeorgInhalation apparatus for animals
US4648393 *Nov 2, 1984Mar 10, 1987Ackrad Laboratories, Inc.Breath activated medication spray
US4776990 *Sep 14, 1987Oct 11, 1988Rhinotherm Netzer SereniMethod and apparatus for nebulizing a liquid
US4815661 *Aug 3, 1987Mar 28, 1989Tomtec N.V.Ultrasonic spraying device
US5063922 *Oct 27, 1988Nov 12, 1991Etala-Hameen Keuhkovammayhdistys R.Y.Ultrasonic atomizer
US5139016 *Dec 29, 1989Aug 18, 1992Sorin Biomedica S.P.A.Process and device for aerosol generation for pulmonary ventilation scintigraphy
US5152456 *Dec 3, 1990Oct 6, 1992Bespak, PlcDispensing apparatus having a perforate outlet member and a vibrating device
US5221025 *May 24, 1990Jun 22, 1993Conceptair AnstaltMethod and mechanical, electrical, or electronic apparatus for dispensing, issuing, or diffusing medicines, fragrances or other liquid or visous substances in the liquid phase or in the gaseous phase
US5259254 *Sep 25, 1991Nov 9, 1993Cetac Technologies, Inc.Sample introduction system for inductively coupled plasma and other gas-phase, or particle, detectors utilizing ultrasonic nebulization, and method of use
US5261601 *Jul 6, 1992Nov 16, 1993Bespak PlcDispensing a liquid as an atomised spray
US5392648 *Dec 17, 1991Feb 28, 1995Minnesota Mining And Manufacturing CompanyDevice for measuring a pre-determined volume of liquid flowing therethrough
US5407424 *Feb 24, 1993Apr 18, 1995Scimed Life Systems, Inc.Angioplasty perfusion pump
US5443059 *Jan 14, 1994Aug 22, 1995Dragerwerk AgUltrasonic atomizer with a metering unit
US5487378 *Dec 17, 1991Jan 30, 1996Minnesota Mining And Manufacturing CompanyFor dispensing droplets of liquid medicament to a patient
US5497763 *Dec 14, 1993Mar 12, 1996Aradigm CorporationTo the lungs
US5507277 *Oct 28, 1994Apr 16, 1996Aradigm CorporationLockout device for controlled release of drug from patient-activateddispenser
US5509404 *Jul 11, 1994Apr 23, 1996Aradigm CorporationInto a patient's airway
US5518179 *Dec 4, 1992May 21, 1996The Technology Partnership LimitedFluid droplets production apparatus and method
US5522385 *Sep 27, 1994Jun 4, 1996Aradigm CorporationDynamic particle size control for aerosolized drug delivery
US5529055 *May 27, 1994Jun 25, 1996L'orealPiezoelectric nebulizing apparatus
US5544646 *May 20, 1994Aug 13, 1996Aradigm CorporationSystems for the intrapulmonary delivery of aerosolized aqueous formulations
US5558085 *Oct 28, 1994Sep 24, 1996Aradigm CorporationIntrapulmonary delivery of peptide drugs
US5586550 *Aug 31, 1995Dec 24, 1996Fluid Propulsion Technologies, Inc.Apparatus for nebulizing a liquid
US5660166 *Apr 10, 1996Aug 26, 1997Aradigm CorporationSystems for the intrapulmonary delivery of aerosolized aqueous formulations
US5672581 *Oct 28, 1994Sep 30, 1997Aradigm CorporationDrug delivery; aerosol, programmed, portable, disposable
US5694919 *Oct 27, 1995Dec 9, 1997Aradigm CorporationHand-held, portable, self-contained aerosol drug delivery system
US5709202 *May 21, 1993Jan 20, 1998Aradigm CorporationIntrapulmonary delivery of aerosolized formulations
US5718222 *May 30, 1995Feb 17, 1998Aradigm CorporationDisposable package for use in aerosolized delivery of drugs
US5724957 *Jul 28, 1995Mar 10, 1998Aradigm CorporationMethod of administering an analgesic drug
US5735263 *Apr 15, 1996Apr 7, 1998Aradigm CorporationLockout device for controlled release of drug from patient-activated dispenser
US5743250 *Nov 22, 1996Apr 28, 1998Aradigm CorporationInsulin delivery enhanced by coached breathing
US5758637 *Feb 21, 1996Jun 2, 1998Aerogen, Inc.Apparatus for nebulizing a liquid
US5771882 *Sep 9, 1996Jun 30, 1998Siemens Elema AbAnesthetic administration apparatus which delivers anesthetic in microdroplets
US5792057 *Nov 26, 1997Aug 11, 1998Aradigm CorporationMethod of creating an image
US5819726 *Feb 4, 1997Oct 13, 1998Aradigm CorporationMethod for the delivery of aerosolized drugs to the lung for the treatment of respiratory disease
US5823178 *Aug 2, 1996Oct 20, 1998Aradigm CorporationDisposable package for use in aerosolized delivery of drugs
US5826570 *Apr 23, 1997Oct 27, 1998Aradigm CorporationHand held device for delivering aerosolized medication to a patient
US5829436 *Jan 27, 1997Nov 3, 1998Aradigm CorporationVentilation imaging using a fine particle aerosol generator
US5873358 *Apr 29, 1998Feb 23, 1999Aradigm CorporationInhaling
US5884620 *Apr 25, 1997Mar 23, 1999Aradigm CorporationInhaled insulin dosage control delivery enhanced by controlling total inhaled volume
US5888477 *Jan 31, 1997Mar 30, 1999Aradigm CorporationUse of monomeric insulin as a means for improving the bioavailability of inhaled insulin
US5910301 *Mar 7, 1997Jun 8, 1999Aradigm CorporationMethod of intrapulmonary administration of a narcotic drug
US5915378 *Oct 27, 1995Jun 29, 1999Aradigm CorporationCreating an aerosolized formulation of insulin
US5934272 *Oct 27, 1995Aug 10, 1999Aradigm CorporationDevice and method of creating aerosolized mist of respiratory drug
US5938117 *Apr 5, 1995Aug 17, 1999Aerogen, Inc.Methods and apparatus for dispensing liquids as an atomized spray
US5941240 *Sep 25, 1998Aug 24, 1999Aradigm CorporationInhaled insulin dosage control delivery enhanced by controlling total inhaled volume
US5950619 *Mar 14, 1996Sep 14, 1999Siemens AktiengesellschaftFor atomizing a fluid
US5957124 *Sep 27, 1995Sep 28, 1999Aradigm CorporationDynamic particle size control for aerosolized drug delivery
US5960792 *Oct 27, 1995Oct 5, 1999Aradigm CorporationDevice for aerosolized delivery of peptide drugs
US5970973 *Apr 29, 1998Oct 26, 1999Aradigm CorporationMethod of delivering insulin lispro
US5970974 *Mar 14, 1996Oct 26, 1999Siemens AktiengesellschaftDosating unit for an ultrasonic atomizer device
US6012450 *Jul 1, 1996Jan 11, 2000Aradigm CorporationIntrapulmonary delivery of hematopoietic drug
US6014969 *Oct 26, 1998Jan 18, 2000Aradigm CorporationDisposable package for use in aerosolized delivery of antibiotics
US6014970 *Jun 11, 1998Jan 18, 2000Aerogen, Inc.Methods and apparatus for storing chemical compounds in a portable inhaler
US6024090 *Jun 1, 1998Feb 15, 2000Aradigm CorporationMethod of treating a diabetic patient by aerosolized administration of insulin lispro
US6085740 *Apr 10, 1998Jul 11, 2000Aerogen, Inc.Liquid dispensing apparatus and methods
US6085753 *Apr 22, 1998Jul 11, 2000Aradigm CorporationInsulin delivery enhanced by coached breathing
US6098615 *Apr 29, 1998Aug 8, 2000Aradigm CorporationMethod of reproducibly effecting a patient's glucose level
US6098620 *Oct 27, 1995Aug 8, 2000Aradigm CorporationDevice for aerosolizing narcotics
US6116233 *Feb 28, 1995Sep 12, 2000Medic-Aid LimitedDrug delivery arrangement
US6123068 *Apr 24, 1998Sep 26, 2000Aradigm CorporationSystems for the intrapulmonary delivery of aerosolized aqueous formulations
US6131567 *Jan 8, 1998Oct 17, 2000Aradigm CorporationMethod of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin
US6138668 *Nov 26, 1997Oct 31, 2000Inhale Therpeutic SystemsMethod and device for delivering aerosolized medicaments
US6167880Aug 20, 1999Jan 2, 2001Aradigm CorporationInhaled insulin dosage control delivery enhanced by controlling total inhaled volume
US6192876Jul 29, 1998Feb 27, 2001Astra AktiebolagInhalation apparatus and method
US6205999Sep 8, 1998Mar 27, 2001Aerogen, Inc.Methods and apparatus for storing chemical compounds in a portable inhaler
US6235177Sep 9, 1999May 22, 2001Aerogen, Inc.Method for the construction of an aperture plate for dispensing liquid droplets
US6250298Sep 7, 2000Jun 26, 2001Aradigm CorporationMethod of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin
US6260549 *Jun 18, 1998Jul 17, 2001Clavius Devices, Inc.Breath-activated metered-dose inhaler
US6318361 *Oct 1, 1999Nov 20, 2001Clavius Devices Inc.Breath-activated metered-dose inhaler
US6408854Apr 21, 2000Jun 25, 2002Aradigm CorporationInsulin delivery enhanced by coached breathing
US6427681Jun 21, 2001Aug 6, 2002Aradigm CorporationMethod of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin
US6431166Feb 15, 2001Aug 13, 2002Aradigm CorporationAerosols; controlling lung delivery
US6431167 *Oct 9, 2001Aug 13, 2002Aradigm CorporationAerosols; controlling lung delivery
US6467476May 18, 2000Oct 22, 2002Aerogen, Inc.Liquid dispensing apparatus and methods
US6530370Sep 16, 1999Mar 11, 2003Instrumentation Corp.Nebulizer apparatus
US6539937Apr 12, 2000Apr 1, 2003Instrumentarium Corp.Method of maximizing the mechanical displacement of a piezoelectric nebulizer apparatus
US6540153May 27, 1999Apr 1, 2003Aerogen, Inc.Methods and apparatus for dispensing liquids as an atomized spray
US6543443Jul 12, 2000Apr 8, 2003Aerogen, Inc.Methods and devices for nebulizing fluids
US6543448May 30, 2000Apr 8, 2003Inhale Therapeutic Systems, Inc.Apparatus and methods for dispersing dry powder medicaments
US6546927Mar 13, 2001Apr 15, 2003Aerogen, Inc.Methods and apparatus for controlling piezoelectric vibration
US6546929Jun 4, 2001Apr 15, 2003Inhale Therapeutic Systems, Inc.Dry powder dispersing apparatus and methods for their use
US6550472Mar 16, 2001Apr 22, 2003Aerogen, Inc.Devices and methods for nebulizing fluids using flow directors
US6554201May 2, 2001Apr 29, 2003Aerogen, Inc.Insert molded aerosol generator and methods
US6598602Jun 19, 2000Jul 29, 2003Siemens-Elema AbMedical nebulizer
US6606989 *May 8, 1998Aug 19, 2003Gsf-Forschungszentrum Fur Umwelt Und Gesundheit GmbhPrecise administration of a medicated aerosol via the lungs
US6629646Dec 7, 1993Oct 7, 2003Aerogen, Inc.Droplet ejector with oscillating tapered aperture
US6640804Aug 15, 2002Nov 4, 2003Aerogen, Inc.Liquid dispensing apparatus and methods
US6647987Jun 18, 2002Nov 18, 2003Aradigm CorporationInsulin delivery enhanced by coached breathing
US6651650 *Apr 9, 1993Nov 25, 2003Omron CorporationUltrasonic atomizer, ultrasonic inhaler and method of controlling same
US6655376 *Nov 18, 1999Dec 2, 2003Pneumoflex Systems L.L.C.Aspiration screening process for assessing post surgery patient's risk for pneumonia
US6679249 *Aug 30, 2001Jan 20, 2004Pneumoflex Systems, L.L.C.Apparatus for treatment of chronic obstructive pulmonary disease and associated method
US6681767May 1, 2000Jan 27, 2004Nektar TherapeuticsMethod and device for delivering aerosolized medicaments
US6688304 *Sep 10, 2001Feb 10, 2004Aradigm CorporationInhaled insulin dosage control delivery enhanced by controlling total inhaled volume
US6729334 *Mar 10, 1999May 4, 2004Trudell Medical LimitedNebulizing catheter system and methods of use and manufacture
US6732944May 2, 2001May 11, 2004Aerogen, Inc.Base isolated nebulizing device and methods
US6755189May 18, 1999Jun 29, 2004Aerogen, Inc.Methods and apparatus for storing chemical compounds in a portable inhaler
US6769626Oct 30, 2000Aug 3, 2004Instrumentarium Corp.Device and method for detecting and controlling liquid supply to an apparatus discharging liquids
US6782886Mar 20, 2001Aug 31, 2004Aerogen, Inc.Metering pumps for an aerosolizer
US6845770Jan 15, 2003Jan 25, 2005Aerogen, Inc.Systems and methods for clearing aerosols from the effective anatomic dead space
US6889690May 8, 2003May 10, 2005Oriel Therapeutics, Inc.Dry powder inhalers, related blister devices, and associated methods of dispensing dry powder substances and fabricating blister packages
US6901929Dec 19, 2002Jun 7, 2005Nektar TherapeuticsAerosolization; comprises pressurization cylinders; drug delivery
US6926208May 2, 2003Aug 9, 2005Aerogen, Inc.Droplet ejector with oscillating tapered aperture
US6948491Mar 20, 2001Sep 27, 2005Aerogen, Inc.Convertible fluid feed system with comformable reservoir and methods
US6978779Apr 19, 2002Dec 27, 2005Instrumentarium Corp.Vibrating element liquid discharging apparatus having gas pressure sensing
US6978941Apr 9, 2004Dec 27, 2005Aerogen, Inc.Base isolated nebulizing device and methods
US6985798Jun 26, 2003Jan 10, 2006Oriel Therapeutics, Inc.Dry powder dose filling systems and related methods
US7021309 *Oct 8, 2003Apr 4, 2006Aradigm CorporationMethod of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin
US7028686 *Nov 4, 2003Apr 18, 2006Aradigm CorporationInhaled insulin dosage control delivery enhanced by controlling total inhaled volume
US7032590Jan 5, 2004Apr 25, 2006Aerogen, Inc.Fluid filled ampoules and methods for their use in aerosolizers
US7040549Mar 21, 2003May 9, 2006Aerogen, Inc.Systems and methods for controlling fluid feed to an aerosol generator
US7066398Mar 30, 2001Jun 27, 2006Aerogen, Inc.Aperture plate and methods for its construction and use
US7083112Jun 6, 2005Aug 1, 2006Aerogen, Inc.Method and apparatus for dispensing liquids as an atomized spray
US7100600Mar 20, 2001Sep 5, 2006Aerogen, Inc.Fluid filled ampoules and methods for their use in aerosolizers
US7104463Oct 6, 2005Sep 12, 2006Aerogen, Inc.Base isolated nebulizing device and methods
US7108197 *May 9, 2005Sep 19, 2006Aerogen, Inc.Droplet ejector with oscillating tapered aperture
US7118010Jun 26, 2003Oct 10, 2006Oriel Therapeutics, Inc.Apparatus, systems and related methods for dispensing and /or evaluating dry powders
US7174888Sep 5, 2003Feb 13, 2007Aerogen, Inc.Liquid dispensing apparatus and methods
US7195011Jun 30, 2004Mar 27, 2007Aerogen, Inc.Convertible fluid feed system with comformable reservoir and methods
US7201163 *Jan 7, 2003Apr 10, 2007The Brigham And Women's Hospital, Inc.Method for altering the body temperature of a patient using a nebulized mist
US7201167 *Mar 14, 2005Apr 10, 2007Aerogen, Inc.Method and composition for the treatment of lung surfactant deficiency or dysfunction
US7267121 *Sep 30, 2004Sep 11, 2007Aerogen, Inc.Aerosol delivery apparatus and method for pressure-assisted breathing systems
US7290541 *Jun 30, 2004Nov 6, 2007Aerogen, Inc.Aerosol delivery apparatus and method for pressure-assisted breathing systems
US7306787Mar 12, 2002Dec 11, 2007Nektar TherapeuticsEngineered particles and methods of use
US7322349 *Jun 18, 2003Jan 29, 2008Aerogen, Inc.Apparatus and methods for the delivery of medicaments to the respiratory system
US7331339Nov 23, 2004Feb 19, 2008Aerogen, Inc.Methods and systems for operating an aerosol generator
US7360536Jan 7, 2003Apr 22, 2008Aerogen, Inc.Devices and methods for nebulizing fluids for inhalation
US7377277Oct 21, 2004May 27, 2008Oriel Therapeutics, Inc.Blister packages with frames and associated methods of fabricating dry powder drug containment systems
US7422013Mar 9, 2005Sep 9, 2008Nektar TherapeuticsDry powder dispersing apparatus and methods for their use
US7428446Jul 12, 2005Sep 23, 2008Oriel Therapeutics, Inc.Dry powder dose filling systems and related methods
US7448375May 17, 2005Nov 11, 2008Aradigm CorporationMethod of treating diabetes mellitus in a patient
US7451761Oct 21, 2004Nov 18, 2008Oriel Therapeutics, Inc.Dry powder inhalers, related blister package indexing and opening mechanisms, and associated methods of dispensing dry powder substances
US7458372Oct 30, 2003Dec 2, 2008Pari Pharma GmbhInhalation therapy device
US7469700Jun 25, 2003Dec 30, 2008Trudell Medical LimitedNebulizing catheter system for delivering an aerosol to a patient
US7472705Jun 25, 2003Jan 6, 2009Trudell Medical LimitedMethods of forming a nebulizing catheter
US7490603 *Nov 21, 2005Feb 17, 2009Aradigm CorporationMethod of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin
US7520278Jan 26, 2005Apr 21, 2009Oriel Therapeutics, Inc.Dry powder inhalers, related blister devices, and associated methods of dispensing dry powder substances and fabricating blister packages
US7600511Oct 30, 2002Oct 13, 2009Novartis Pharma AgApparatus and methods for delivery of medicament to a respiratory system
US7622510 *Oct 15, 2003Nov 24, 2009Christophe ArnaudMethod and device for making a dispersion or an emulsion
US7628339May 5, 2006Dec 8, 2009Novartis Pharma AgSystems and methods for controlling fluid feed to an aerosol generator
US7628978Aug 19, 2003Dec 8, 2009Novartis Pharma AgStabilized preparations for use in metered dose inhalers
US7677411Jun 27, 2003Mar 16, 2010Oriel Therapeutics, Inc.Apparatus, systems and related methods for processing, dispensing and/or evaluatingl dry powders
US7677467 *Apr 20, 2005Mar 16, 2010Novartis Pharma AgMethods and devices for aerosolizing medicament
US7712680 *Jan 30, 2006May 11, 2010Sono-Tek CorporationUltrasonic atomizing nozzle and method
US7748377Oct 30, 2007Jul 6, 2010Novartis AgMethods and systems for operating an aerosol generator
US7771642Apr 1, 2005Aug 10, 2010Novartis AgMethods of making an apparatus for providing aerosol for medical treatment
US7871598May 10, 2000Jan 18, 2011Novartis Agexhibit improved stability and dispersability over the shelf life of the composition; microparticles are simple to produce without the need of the formation of an emulsion or the use of an oil as a blowing agent
US7883031May 20, 2004Feb 8, 2011James F. Collins, Jr.Ophthalmic drug delivery system
US7914517Nov 1, 2004Mar 29, 2011Trudell Medical InternationalSystem and method for manipulating a catheter for delivering a substance to a body cavity
US7931212Jul 31, 2003Apr 26, 2011Pari Pharma GmbhFluid droplet production apparatus and method
US7946291 *Apr 20, 2004May 24, 2011Novartis AgVentilation systems and methods employing aerosol generators
US7958887Mar 8, 2007Jun 14, 2011Aradigm CorporationNozzle pore configuration for intrapulmonary delivery of aerosolized formulations
US7971588Mar 24, 2005Jul 5, 2011Novartis AgMethods and systems for operating an aerosol generator
US8012136Jan 26, 2007Sep 6, 2011Optimyst Systems, Inc.Ophthalmic fluid delivery device and method of operation
US8161969Mar 21, 2008Apr 24, 2012Novartis AgDry powder dispersing apparatus and methods for their use
US8168223Jun 21, 2001May 1, 2012Novartis Pharma AgEngineered particles and methods of use
US8196573Jan 23, 2008Jun 12, 2012Novartis AgMethods and systems for operating an aerosol generator
US8201554Mar 13, 2009Jun 19, 2012Injet Digital Aerosols LimitedInhalation device having an optimized air flow path
US8246934Sep 3, 2010Aug 21, 2012Novartis AgRespiratory dispersion for metered dose inhalers comprising perforated microstructures
US8332020Jan 28, 2011Dec 11, 2012Proteus Digital Health, Inc.Two-wrist data gathering system
US8336545Jan 16, 2007Dec 25, 2012Novartis Pharma AgMethods and systems for operating an aerosol generator
US8348177Jun 15, 2009Jan 8, 2013Davicon CorporationLiquid dispensing apparatus using a passive liquid metering method
US8349294Dec 14, 2010Jan 8, 2013Novartis AgStable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use
US8371290Oct 9, 2008Feb 12, 2013General Electric CompanyDevice for delivery and regulation of volatile fluids into inspiratory gas
US8371299Apr 10, 2008Feb 12, 2013Respironics Respiratory Drug DeliveryVentilator aerosol delivery
US8398001Jun 19, 2006Mar 19, 2013Novartis AgAperture plate and methods for its construction and use
US8404217Jul 22, 2005Mar 26, 2013Novartis Agantifungal administered via inhalation; good dispersibility and storage stability; efficiently delivered to the deep lung; treating pulmonary aspergillosis with amphotericin B-containing formulations
US8419638Nov 18, 2008Apr 16, 2013Proteus Digital Health, Inc.Body-associated fluid transport structure evaluation devices
US8511581Mar 8, 2011Aug 20, 2013Pari Pharma GmbhFluid droplet production apparatus and method
US8539944Apr 8, 2008Sep 24, 2013Novartis AgDevices and methods for nebulizing fluids for inhalation
US8545463Jan 26, 2007Oct 1, 2013Optimyst Systems Inc.Ophthalmic fluid reservoir assembly for use with an ophthalmic fluid delivery device
US8561604Feb 12, 2007Oct 22, 2013Novartis AgLiquid dispensing apparatus and methods
US8578931Apr 18, 2000Nov 12, 2013Novartis AgMethods and apparatus for storing chemical compounds in a portable inhaler
US8616195Apr 27, 2004Dec 31, 2013Novartis AgNebuliser for the production of aerosolized medication
US8684980Jul 15, 2011Apr 1, 2014Corinthian Ophthalmic, Inc.Drop generating device
US8709484Oct 24, 2008Apr 29, 2014Novartis AgPhospholipid-based powders for drug delivery
US8715623Oct 31, 2007May 6, 2014Novartis AgPulmonary delivery of aminoglycoside
US8733343 *Oct 29, 2007May 27, 2014Universidad De SevillaDevice and method for creating aerosols for drug delivery
US8733935Jul 15, 2011May 27, 2014Corinthian Ophthalmic, Inc.Method and system for performing remote treatment and monitoring
US20090288659 *May 13, 2009Nov 26, 2009Heikki HaveriApparatus, system and method for administering an anesthetic agent for a subject breathing
US20130108748 *Oct 31, 2012May 2, 2013Pepsico., Inc.Dispensing Nozzle with an Ultrasound Activator
DE4300880A1 *Jan 15, 1993Jul 21, 1994Draegerwerk AgUltraschallvernebler mit Dosiereinheit
EP0156409A2 *Feb 18, 1985Oct 2, 1985Jean Michel AnthonyDevice for moistening parts of the human body
EP0186280A2 *Oct 25, 1985Jul 2, 1986Robert LandisBreath activated medication spray
EP0200258A2 *Apr 17, 1986Nov 5, 1986Jean Michel AnthonyUltrasonic spraying device
EP0232235A2 *Jan 23, 1987Aug 12, 1987A/S GEA Farmaceutisk FabrikMedical dosing device for discharge of atomized medicament for inhalation air
EP0642802A2 *Aug 5, 1994Mar 15, 1995Disetronic AgInhalation device
EP0844027A1 *Aug 5, 1996May 27, 1998Omron CorporationAtomization apparatus and method utilizing surface acoustic waves
EP1066850A1 *Apr 28, 2000Jan 10, 2001Siemens Elema ABMedical Nebulizer
EP1219313A1Dec 29, 2000Jul 3, 2002Instrumentarium CorporationLiquid discharging apparatus and magneto-shape-memory type valve
EP1219314A1Dec 29, 2000Jul 3, 2002Instrumentarium CorporationLiquid discharge apparatus having magnetic valve
EP1227856A1 *Oct 27, 2000Aug 7, 2002PARI GmbH Spezialisten für effektive InhalationInhalation nebulizer
EP1310268A2 *Jul 10, 1995May 14, 2003Aradigm CorporationIntrapulmonary drug delivery within therapeutically relevant inspiratory flow/volume values
EP1694392A2 *Nov 24, 2004Aug 30, 2006Robert E. CoifmanDevices for measuring inspiratory airflow
EP2050478A1 *Oct 16, 2007Apr 22, 2009GE Healthcare Finland OyDevice for delivery and regulation of volatile fluids into inspiratory gas
EP2050479A2 *May 20, 2008Apr 22, 2009General Electric CompanyApparatus, system and method for admistering an anesthetic agent for a subject breathing
EP2119465A1 *May 16, 2008Nov 18, 2009Markos Mefar S.P.A.Nebulizer with breathing phase detecting sensor for delivering nebulized drugs to a user
WO1989006147A1 *Oct 27, 1988Jul 13, 1989Etelae Haemeen KeuhkovammayhdiUltrasonic atomizer
WO1992011050A1 *Dec 17, 1991Jul 9, 1992Minnesota Mining & MfgInhaler
WO1992011512A1 *Dec 17, 1991Jul 9, 1992Minnesota Mining & MfgDevice for measuring a pre-determined volume of liquid flowing there through
WO1996001663A1 *Jul 10, 1995Jan 25, 1996Aradigm CorpIntrapulmonary drug delivery within therapeutically relevant inspiratory flow/volume values
WO1996013290A1 *Oct 27, 1995May 9, 1996Aradigm CorpDevice for aerosolized delivery of peptide drugs
WO1996013291A1 *Oct 27, 1995May 9, 1996Aradigm CorpDevice for aerosolizing narcotics
WO1996013292A1 *Oct 27, 1995May 9, 1996Aradigm CorpDevice and method of creating aerosolized mist of respiratory drug
WO1996028205A1 *Mar 14, 1996Sep 19, 1996Siemens AgUltrasonic atomizer device with removable precision dosing unit
WO1996028206A1 *Mar 14, 1996Sep 19, 1996Siemens AgUltrasonic atomizer device with removable precision dosating unit
WO1996030068A1 *Mar 15, 1996Oct 3, 1996Aradigm CorpIntrapulmonary delivery of hematopoietic drug
WO1996031289A1Apr 3, 1996Oct 10, 1996Fluid Propulsion Techn IncMethods and apparatus for dispensing liquids as an atomized spray
WO1997018846A1 *Nov 18, 1996May 29, 1997R & D Injector AgNebulizing device
WO1997031721A1 *Feb 27, 1997Sep 4, 1997Hopkins Andrew DavidA nebuliser
WO2001019437A1Sep 8, 2000Mar 22, 2001Instrumentarium CorpNebulizer apparatus
WO2001032246A1 *Nov 3, 2000May 10, 2001Pari GmbhInhalation nebuliser
WO2001076762A2Apr 4, 2001Oct 18, 2001Instrumentarium CorpMethod of maximizing the mechanical displacement of a piezoelectric nebulizer apparatus
WO2002036269A1Oct 12, 2001May 10, 2002Instrumentarium CorpDevice and method for detecting and controlling liquid supply to an apparatus discharging liquid
WO2002087772A1 *May 1, 2002Nov 7, 2002Aerogen IncCymbal-shaped actuator for a nebulizing element
WO2003059423A1 *Jan 15, 2003Jul 24, 2003Aerogen IncSystems and methods for clearing aerosols from the effective anatomic dead space
WO2005011574A2 *Jul 23, 2004Feb 10, 2005Robert E CoifmanMicroporous membrane nebulizers
WO2005051177A2 *Nov 24, 2004Jun 9, 2005Robert E CoifmanDevices for measuring inspiratory airflow
WO2005102431A2 *Apr 20, 2005Nov 3, 2005Aerogen IncAerosol delivery apparatus for pressure assisted breathing
WO2007106386A2Mar 9, 2007Sep 20, 2007Aradgim CorpNozzle pore configuration for intrapulmonary delivery of aerosolized formulations
WO2012156724A2May 16, 2012Nov 22, 2012The Technology Partnership PlcSeparable membrane improvements
Classifications
U.S. Classification128/200.16, 239/102.2
International ClassificationB05B17/06, A61M15/00, A61M11/00
Cooperative ClassificationB05B17/063, B05B17/0623, A61M15/0085, A61M2011/001
European ClassificationB05B17/06B2B, A61M15/00F, B05B17/06B2