|Número de publicación||US3812854 A|
|Tipo de publicación||Concesión|
|Fecha de publicación||28 May 1974|
|Fecha de presentación||20 Oct 1972|
|Fecha de prioridad||20 Oct 1972|
|Número de publicación||US 3812854 A, US 3812854A, US-A-3812854, US3812854 A, US3812854A|
|Inventores||R Buckles, M Keller, A Michaels|
|Cesionario original||R Buckles, M Keller, A Michaels|
|Exportar cita||BiBTeX, EndNote, RefMan|
|Citas de patentes (8), Citada por (306), Clasificaciones (12)|
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet|
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  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  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  Filed: Oct. 20, 1972  App]. No.: 299,194
 US. Cl 128/194, 128/D1G. 2, 239/102  Int. Cl A6lm 15/00  Field of Search 128/194, DIG. 2, 172, 173, 128/193, 145.8, 145.6; 259/D1G. 44; 239/102, 4, 338
 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.
|Patente citada||Fecha de presentación||Fecha de publicación||Solicitante||Título|
|US2658169 *||14 Mar 1949||3 Nov 1953||Centre Nat Rech Scient||Production of aerosols|
|US2949900 *||2 Jun 1958||23 Ago 1960||Albert G Bodine||Sonic liquid sprayer|
|US3121534 *||29 Sep 1960||18 Feb 1964||Exxon Research Engineering Co||Supersonic liquid atomizer and electronic oscillator therefor|
|US3214101 *||31 Mar 1964||26 Oct 1965||Little Inc A||Apparatus for atomizing a liquid|
|US3243122 *||24 Feb 1965||29 Mar 1966||Alvin A Snaper||Ultrasonic spray apparatus|
|US3400892 *||2 Dic 1965||10 Sep 1968||Battelle Development Corp||Resonant vibratory apparatus|
|US3561444 *||22 May 1968||9 Feb 1971||Bio Logics Inc||Ultrasonic drug nebulizer|
|US3653379 *||20 Ago 1970||4 Abr 1972||Glenn Joseph G||Adjustable pressure ippb ventilator|
|Patente citante||Fecha de presentación||Fecha de publicación||Solicitante||Título|
|US3912168 *||30 Ene 1975||14 Oct 1975||Teledyne Ind Inc Teledyne Aqua||Irrigation lavage|
|US4106503 *||11 Mar 1977||15 Ago 1978||Richard R. Rosenthal||Metering system for stimulating bronchial spasm|
|US4109863 *||17 Ago 1977||29 Ago 1978||The United States Of America As Represented By The United States Department Of Energy||Apparatus for ultrasonic nebulization|
|US4119096 *||24 Ago 1976||10 Oct 1978||Siemens Aktiengesellschaft||Medical inhalation device for the treatment of diseases of the respiratory tract|
|US4261512 *||20 Feb 1980||14 Abr 1981||Boehringer Ingelheim Gmbh||Inhalation aerosol spray device|
|US4292973 *||3 Ene 1980||6 Oct 1981||Kabushiki Kaisha Kurio-Medikaru||Apparatus for refrigeration treatment|
|US4348873 *||23 Jun 1981||14 Sep 1982||Kabushiki Kaisha Kurio-Medikaru||Apparatus for refrigeration treatment|
|US4412538 *||31 Jul 1981||1 Nov 1983||Kabushiki Kaisha Kurio-Medikaru||Apparatus for refrigeration treatment|
|US4541966 *||24 Ago 1984||17 Sep 1985||Penlon Limited||Gas humidifying apparatus and method|
|US4546768 *||14 Dic 1982||15 Oct 1985||Feierabend Georg||Inhalation apparatus for animals|
|US4648393 *||2 Nov 1984||10 Mar 1987||Ackrad Laboratories, Inc.||Breath activated medication spray|
|US4776990 *||14 Sep 1987||11 Oct 1988||Rhinotherm Netzer Sereni||Method and apparatus for nebulizing a liquid|
|US4815661 *||3 Ago 1987||28 Mar 1989||Tomtec N.V.||Ultrasonic spraying device|
|US5063922 *||27 Oct 1988||12 Nov 1991||Etala-Hameen Keuhkovammayhdistys R.Y.||Ultrasonic atomizer|
|US5139016 *||29 Dic 1989||18 Ago 1992||Sorin Biomedica S.P.A.||Process and device for aerosol generation for pulmonary ventilation scintigraphy|
|US5152456 *||3 Dic 1990||6 Oct 1992||Bespak, Plc||Dispensing apparatus having a perforate outlet member and a vibrating device|
|US5221025 *||24 May 1990||22 Jun 1993||Conceptair Anstalt||Method 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 *||25 Sep 1991||9 Nov 1993||Cetac Technologies, Inc.||Sample introduction system for inductively coupled plasma and other gas-phase, or particle, detectors utilizing ultrasonic nebulization, and method of use|
|US5261601 *||6 Jul 1992||16 Nov 1993||Bespak Plc||Liquid dispensing apparatus having a vibrating perforate membrane|
|US5392648 *||17 Dic 1991||28 Feb 1995||Minnesota Mining And Manufacturing Company||Device for measuring a pre-determined volume of liquid flowing therethrough|
|US5407424 *||24 Feb 1993||18 Abr 1995||Scimed Life Systems, Inc.||Angioplasty perfusion pump|
|US5443059 *||14 Ene 1994||22 Ago 1995||Dragerwerk Ag||Ultrasonic atomizer with a metering unit|
|US5487378 *||17 Dic 1991||30 Ene 1996||Minnesota Mining And Manufacturing Company||Inhaler|
|US5497763 *||14 Dic 1993||12 Mar 1996||Aradigm Corporation||Disposable package for intrapulmonary delivery of aerosolized formulations|
|US5507277 *||28 Oct 1994||16 Abr 1996||Aradigm Corporation||Lockout device for controlled release of drug from patient-activateddispenser|
|US5509404 *||11 Jul 1994||23 Abr 1996||Aradigm Corporation||Intrapulmonary drug delivery within therapeutically relevant inspiratory flow/volume values|
|US5518179 *||4 Dic 1992||21 May 1996||The Technology Partnership Limited||Fluid droplets production apparatus and method|
|US5522385 *||27 Sep 1994||4 Jun 1996||Aradigm Corporation||Dynamic particle size control for aerosolized drug delivery|
|US5529055 *||27 May 1994||25 Jun 1996||L'oreal||Piezoelectric nebulizing apparatus|
|US5544646 *||20 May 1994||13 Ago 1996||Aradigm Corporation||Systems for the intrapulmonary delivery of aerosolized aqueous formulations|
|US5558085 *||28 Oct 1994||24 Sep 1996||Aradigm Corporation||Intrapulmonary delivery of peptide drugs|
|US5586550 *||31 Ago 1995||24 Dic 1996||Fluid Propulsion Technologies, Inc.||Apparatus and methods for the delivery of therapeutic liquids to the respiratory system|
|US5660166 *||10 Abr 1996||26 Ago 1997||Aradigm Corporation||Systems for the intrapulmonary delivery of aerosolized aqueous formulations|
|US5672581 *||28 Oct 1994||30 Sep 1997||Aradigm Corporation||Method of administration of insulin|
|US5694919 *||27 Oct 1995||9 Dic 1997||Aradigm Corporation||Lockout device for controlled release of drug from patient-activated dispenser|
|US5709202 *||21 May 1993||20 Ene 1998||Aradigm Corporation||Intrapulmonary delivery of aerosolized formulations|
|US5718222 *||30 May 1995||17 Feb 1998||Aradigm Corporation||Disposable package for use in aerosolized delivery of drugs|
|US5724957 *||28 Jul 1995||10 Mar 1998||Aradigm Corporation||Intrapulmonary delivery of narcotics|
|US5735263 *||15 Abr 1996||7 Abr 1998||Aradigm Corporation||Lockout device for controlled release of drug from patient-activated dispenser|
|US5743250 *||22 Nov 1996||28 Abr 1998||Aradigm Corporation||Insulin delivery enhanced by coached breathing|
|US5758637 *||21 Feb 1996||2 Jun 1998||Aerogen, Inc.||Liquid dispensing apparatus and methods|
|US5771882 *||9 Sep 1996||30 Jun 1998||Siemens Elema Ab||Anesthetic administration apparatus which delivers anesthetic in microdroplets|
|US5792057 *||26 Nov 1997||11 Ago 1998||Aradigm Corporation||Ventilation imaging using a fine particle aerosol generator|
|US5819726 *||4 Feb 1997||13 Oct 1998||Aradigm Corporation||Method for the delivery of aerosolized drugs to the lung for the treatment of respiratory disease|
|US5823178 *||2 Ago 1996||20 Oct 1998||Aradigm Corporation||Disposable package for use in aerosolized delivery of drugs|
|US5826570 *||23 Abr 1997||27 Oct 1998||Aradigm Corporation||Delivery of aerosol medications for inspiration|
|US5829436 *||27 Ene 1997||3 Nov 1998||Aradigm Corporation||Ventilation imaging using a fine particle aerosol generator|
|US5873358 *||29 Abr 1998||23 Feb 1999||Aradigm Corporation||Method of maintaining a diabetic patient's blood glucose level in a desired range|
|US5884620 *||25 Abr 1997||23 Mar 1999||Aradigm Corporation||Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume|
|US5888477 *||31 Ene 1997||30 Mar 1999||Aradigm Corporation||Use of monomeric insulin as a means for improving the bioavailability of inhaled insulin|
|US5910301 *||7 Mar 1997||8 Jun 1999||Aradigm Corporation||Method of intrapulmonary administration of a narcotic drug|
|US5915378 *||27 Oct 1995||29 Jun 1999||Aradigm Corporation||Creating an aerosolized formulation of insulin|
|US5934272 *||27 Oct 1995||10 Ago 1999||Aradigm Corporation||Device and method of creating aerosolized mist of respiratory drug|
|US5938117 *||5 Abr 1995||17 Ago 1999||Aerogen, Inc.||Methods and apparatus for dispensing liquids as an atomized spray|
|US5941240 *||25 Sep 1998||24 Ago 1999||Aradigm Corporation||Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume|
|US5950619 *||14 Mar 1996||14 Sep 1999||Siemens Aktiengesellschaft||Ultrasonic atomizer device with removable precision dosating unit|
|US5957124 *||27 Sep 1995||28 Sep 1999||Aradigm Corporation||Dynamic particle size control for aerosolized drug delivery|
|US5960792 *||27 Oct 1995||5 Oct 1999||Aradigm Corporation||Device for aerosolized delivery of peptide drugs|
|US5970973 *||29 Abr 1998||26 Oct 1999||Aradigm Corporation||Method of delivering insulin lispro|
|US5970974 *||14 Mar 1996||26 Oct 1999||Siemens Aktiengesellschaft||Dosating unit for an ultrasonic atomizer device|
|US6012450 *||1 Jul 1996||11 Ene 2000||Aradigm Corporation||Intrapulmonary delivery of hematopoietic drug|
|US6014969 *||26 Oct 1998||18 Ene 2000||Aradigm Corporation||Disposable package for use in aerosolized delivery of antibiotics|
|US6014970 *||11 Jun 1998||18 Ene 2000||Aerogen, Inc.||Methods and apparatus for storing chemical compounds in a portable inhaler|
|US6024090 *||1 Jun 1998||15 Feb 2000||Aradigm Corporation||Method of treating a diabetic patient by aerosolized administration of insulin lispro|
|US6085740 *||10 Abr 1998||11 Jul 2000||Aerogen, Inc.||Liquid dispensing apparatus and methods|
|US6085753 *||22 Abr 1998||11 Jul 2000||Aradigm Corporation||Insulin delivery enhanced by coached breathing|
|US6098615 *||29 Abr 1998||8 Ago 2000||Aradigm Corporation||Method of reproducibly effecting a patient's glucose level|
|US6098620 *||27 Oct 1995||8 Ago 2000||Aradigm Corporation||Device for aerosolizing narcotics|
|US6116233 *||28 Feb 1995||12 Sep 2000||Medic-Aid Limited||Drug delivery arrangement|
|US6123068 *||24 Abr 1998||26 Sep 2000||Aradigm Corporation||Systems for the intrapulmonary delivery of aerosolized aqueous formulations|
|US6131567 *||8 Ene 1998||17 Oct 2000||Aradigm Corporation||Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin|
|US6138668 *||26 Nov 1997||31 Oct 2000||Inhale Therpeutic Systems||Method and device for delivering aerosolized medicaments|
|US6167880||20 Ago 1999||2 Ene 2001||Aradigm Corporation||Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume|
|US6192876||29 Jul 1998||27 Feb 2001||Astra Aktiebolag||Inhalation apparatus and method|
|US6205999||8 Sep 1998||27 Mar 2001||Aerogen, Inc.||Methods and apparatus for storing chemical compounds in a portable inhaler|
|US6235177||9 Sep 1999||22 May 2001||Aerogen, Inc.||Method for the construction of an aperture plate for dispensing liquid droplets|
|US6250298||7 Sep 2000||26 Jun 2001||Aradigm Corporation||Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin|
|US6260549 *||18 Jun 1998||17 Jul 2001||Clavius Devices, Inc.||Breath-activated metered-dose inhaler|
|US6318361 *||1 Oct 1999||20 Nov 2001||Clavius Devices Inc.||Breath-activated metered-dose inhaler|
|US6408854||21 Abr 2000||25 Jun 2002||Aradigm Corporation||Insulin delivery enhanced by coached breathing|
|US6427681||21 Jun 2001||6 Ago 2002||Aradigm Corporation||Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin|
|US6431166||15 Feb 2001||13 Ago 2002||Aradigm Corporation||Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin|
|US6431167 *||9 Oct 2001||13 Ago 2002||Aradigm Corporation||Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin|
|US6467476||18 May 2000||22 Oct 2002||Aerogen, Inc.||Liquid dispensing apparatus and methods|
|US6530370||16 Sep 1999||11 Mar 2003||Instrumentation Corp.||Nebulizer apparatus|
|US6539937||12 Abr 2000||1 Abr 2003||Instrumentarium Corp.||Method of maximizing the mechanical displacement of a piezoelectric nebulizer apparatus|
|US6540153||27 May 1999||1 Abr 2003||Aerogen, Inc.||Methods and apparatus for dispensing liquids as an atomized spray|
|US6543443||12 Jul 2000||8 Abr 2003||Aerogen, Inc.||Methods and devices for nebulizing fluids|
|US6543448||30 May 2000||8 Abr 2003||Inhale Therapeutic Systems, Inc.||Apparatus and methods for dispersing dry powder medicaments|
|US6546927||13 Mar 2001||15 Abr 2003||Aerogen, Inc.||Methods and apparatus for controlling piezoelectric vibration|
|US6546929||4 Jun 2001||15 Abr 2003||Inhale Therapeutic Systems, Inc.||Dry powder dispersing apparatus and methods for their use|
|US6550472||16 Mar 2001||22 Abr 2003||Aerogen, Inc.||Devices and methods for nebulizing fluids using flow directors|
|US6554201||2 May 2001||29 Abr 2003||Aerogen, Inc.||Insert molded aerosol generator and methods|
|US6598602||19 Jun 2000||29 Jul 2003||Siemens-Elema Ab||Medical nebulizer|
|US6606989 *||8 May 1998||19 Ago 2003||Gsf-Forschungszentrum Fur Umwelt Und Gesundheit Gmbh||Precise administration of a medicated aerosol via the lungs|
|US6629646||7 Dic 1993||7 Oct 2003||Aerogen, Inc.||Droplet ejector with oscillating tapered aperture|
|US6640804||15 Ago 2002||4 Nov 2003||Aerogen, Inc.||Liquid dispensing apparatus and methods|
|US6647987||18 Jun 2002||18 Nov 2003||Aradigm Corporation||Insulin delivery enhanced by coached breathing|
|US6651650 *||9 Abr 1993||25 Nov 2003||Omron Corporation||Ultrasonic atomizer, ultrasonic inhaler and method of controlling same|
|US6655376 *||18 Nov 1999||2 Dic 2003||Pneumoflex Systems L.L.C.||Aspiration screening process for assessing post surgery patient's risk for pneumonia|
|US6679249 *||30 Ago 2001||20 Ene 2004||Pneumoflex Systems, L.L.C.||Apparatus for treatment of chronic obstructive pulmonary disease and associated method|
|US6681767||1 May 2000||27 Ene 2004||Nektar Therapeutics||Method and device for delivering aerosolized medicaments|
|US6688304 *||10 Sep 2001||10 Feb 2004||Aradigm Corporation||Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume|
|US6729334 *||10 Mar 1999||4 May 2004||Trudell Medical Limited||Nebulizing catheter system and methods of use and manufacture|
|US6732944||2 May 2001||11 May 2004||Aerogen, Inc.||Base isolated nebulizing device and methods|
|US6755189||18 May 1999||29 Jun 2004||Aerogen, Inc.||Methods and apparatus for storing chemical compounds in a portable inhaler|
|US6769626||30 Oct 2000||3 Ago 2004||Instrumentarium Corp.||Device and method for detecting and controlling liquid supply to an apparatus discharging liquids|
|US6782886||20 Mar 2001||31 Ago 2004||Aerogen, Inc.||Metering pumps for an aerosolizer|
|US6845770||15 Ene 2003||25 Ene 2005||Aerogen, Inc.||Systems and methods for clearing aerosols from the effective anatomic dead space|
|US6889690||8 May 2003||10 May 2005||Oriel Therapeutics, Inc.||Dry powder inhalers, related blister devices, and associated methods of dispensing dry powder substances and fabricating blister packages|
|US6901929||19 Dic 2002||7 Jun 2005||Nektar Therapeutics||Dry powder dispersing apparatus and methods for their use|
|US6926208||2 May 2003||9 Ago 2005||Aerogen, Inc.||Droplet ejector with oscillating tapered aperture|
|US6948491||20 Mar 2001||27 Sep 2005||Aerogen, Inc.||Convertible fluid feed system with comformable reservoir and methods|
|US6978779||19 Abr 2002||27 Dic 2005||Instrumentarium Corp.||Vibrating element liquid discharging apparatus having gas pressure sensing|
|US6978941||9 Abr 2004||27 Dic 2005||Aerogen, Inc.||Base isolated nebulizing device and methods|
|US6985798||26 Jun 2003||10 Ene 2006||Oriel Therapeutics, Inc.||Dry powder dose filling systems and related methods|
|US7021309 *||8 Oct 2003||4 Abr 2006||Aradigm Corporation||Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin|
|US7028686 *||4 Nov 2003||18 Abr 2006||Aradigm Corporation||Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume|
|US7032590||5 Ene 2004||25 Abr 2006||Aerogen, Inc.||Fluid filled ampoules and methods for their use in aerosolizers|
|US7040549||21 Mar 2003||9 May 2006||Aerogen, Inc.||Systems and methods for controlling fluid feed to an aerosol generator|
|US7066398||30 Mar 2001||27 Jun 2006||Aerogen, Inc.||Aperture plate and methods for its construction and use|
|US7083112||6 Jun 2005||1 Ago 2006||Aerogen, Inc.||Method and apparatus for dispensing liquids as an atomized spray|
|US7100600||20 Mar 2001||5 Sep 2006||Aerogen, Inc.||Fluid filled ampoules and methods for their use in aerosolizers|
|US7104463||6 Oct 2005||12 Sep 2006||Aerogen, Inc.||Base isolated nebulizing device and methods|
|US7108197 *||9 May 2005||19 Sep 2006||Aerogen, Inc.||Droplet ejector with oscillating tapered aperture|
|US7118010||26 Jun 2003||10 Oct 2006||Oriel Therapeutics, Inc.||Apparatus, systems and related methods for dispensing and /or evaluating dry powders|
|US7174888||5 Sep 2003||13 Feb 2007||Aerogen, Inc.||Liquid dispensing apparatus and methods|
|US7195011||30 Jun 2004||27 Mar 2007||Aerogen, Inc.||Convertible fluid feed system with comformable reservoir and methods|
|US7201163 *||7 Ene 2003||10 Abr 2007||The Brigham And Women's Hospital, Inc.||Method for altering the body temperature of a patient using a nebulized mist|
|US7201167 *||14 Mar 2005||10 Abr 2007||Aerogen, Inc.||Method and composition for the treatment of lung surfactant deficiency or dysfunction|
|US7267121 *||30 Sep 2004||11 Sep 2007||Aerogen, Inc.||Aerosol delivery apparatus and method for pressure-assisted breathing systems|
|US7290541 *||30 Jun 2004||6 Nov 2007||Aerogen, Inc.||Aerosol delivery apparatus and method for pressure-assisted breathing systems|
|US7306787||12 Mar 2002||11 Dic 2007||Nektar Therapeutics||Engineered particles and methods of use|
|US7322349 *||18 Jun 2003||29 Ene 2008||Aerogen, Inc.||Apparatus and methods for the delivery of medicaments to the respiratory system|
|US7331339||23 Nov 2004||19 Feb 2008||Aerogen, Inc.||Methods and systems for operating an aerosol generator|
|US7360536||7 Ene 2003||22 Abr 2008||Aerogen, Inc.||Devices and methods for nebulizing fluids for inhalation|
|US7377277||21 Oct 2004||27 May 2008||Oriel Therapeutics, Inc.||Blister packages with frames and associated methods of fabricating dry powder drug containment systems|
|US7422013||9 Mar 2005||9 Sep 2008||Nektar Therapeutics||Dry powder dispersing apparatus and methods for their use|
|US7428446||12 Jul 2005||23 Sep 2008||Oriel Therapeutics, Inc.||Dry powder dose filling systems and related methods|
|US7448375||17 May 2005||11 Nov 2008||Aradigm Corporation||Method of treating diabetes mellitus in a patient|
|US7451761||21 Oct 2004||18 Nov 2008||Oriel Therapeutics, Inc.||Dry powder inhalers, related blister package indexing and opening mechanisms, and associated methods of dispensing dry powder substances|
|US7458372||30 Oct 2003||2 Dic 2008||Pari Pharma Gmbh||Inhalation therapy device|
|US7469700||25 Jun 2003||30 Dic 2008||Trudell Medical Limited||Nebulizing catheter system for delivering an aerosol to a patient|
|US7472705||25 Jun 2003||6 Ene 2009||Trudell Medical Limited||Methods of forming a nebulizing catheter|
|US7490603 *||21 Nov 2005||17 Feb 2009||Aradigm Corporation||Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin|
|US7520278||26 Ene 2005||21 Abr 2009||Oriel Therapeutics, Inc.||Dry powder inhalers, related blister devices, and associated methods of dispensing dry powder substances and fabricating blister packages|
|US7600511||30 Oct 2002||13 Oct 2009||Novartis Pharma Ag||Apparatus and methods for delivery of medicament to a respiratory system|
|US7622510 *||15 Oct 2003||24 Nov 2009||Christophe Arnaud||Method and device for making a dispersion or an emulsion|
|US7628339||5 May 2006||8 Dic 2009||Novartis Pharma Ag||Systems and methods for controlling fluid feed to an aerosol generator|
|US7628978||19 Ago 2003||8 Dic 2009||Novartis Pharma Ag||Stabilized preparations for use in metered dose inhalers|
|US7677411||27 Jun 2003||16 Mar 2010||Oriel Therapeutics, Inc.||Apparatus, systems and related methods for processing, dispensing and/or evaluatingl dry powders|
|US7677467 *||20 Abr 2005||16 Mar 2010||Novartis Pharma Ag||Methods and devices for aerosolizing medicament|
|US7712680 *||30 Ene 2006||11 May 2010||Sono-Tek Corporation||Ultrasonic atomizing nozzle and method|
|US7748377||30 Oct 2007||6 Jul 2010||Novartis Ag||Methods and systems for operating an aerosol generator|
|US7771642||1 Abr 2005||10 Ago 2010||Novartis Ag||Methods of making an apparatus for providing aerosol for medical treatment|
|US7871598||10 May 2000||18 Ene 2011||Novartis Ag||Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use|
|US7883031||20 May 2004||8 Feb 2011||James F. Collins, Jr.||Ophthalmic drug delivery system|
|US7914517||1 Nov 2004||29 Mar 2011||Trudell Medical International||System and method for manipulating a catheter for delivering a substance to a body cavity|
|US7931212||31 Jul 2003||26 Abr 2011||Pari Pharma Gmbh||Fluid droplet production apparatus and method|
|US7946291 *||20 Abr 2004||24 May 2011||Novartis Ag||Ventilation systems and methods employing aerosol generators|
|US7958887||8 Mar 2007||14 Jun 2011||Aradigm Corporation||Nozzle pore configuration for intrapulmonary delivery of aerosolized formulations|
|US7971588||24 Mar 2005||5 Jul 2011||Novartis Ag||Methods and systems for operating an aerosol generator|
|US8012136||26 Ene 2007||6 Sep 2011||Optimyst Systems, Inc.||Ophthalmic fluid delivery device and method of operation|
|US8161969||21 Mar 2008||24 Abr 2012||Novartis Ag||Dry powder dispersing apparatus and methods for their use|
|US8168223||21 Jun 2001||1 May 2012||Novartis Pharma Ag||Engineered particles and methods of use|
|US8196573||23 Ene 2008||12 Jun 2012||Novartis Ag||Methods and systems for operating an aerosol generator|
|US8201554||13 Mar 2009||19 Jun 2012||Injet Digital Aerosols Limited||Inhalation device having an optimized air flow path|
|US8246934||3 Sep 2010||21 Ago 2012||Novartis Ag||Respiratory dispersion for metered dose inhalers comprising perforated microstructures|
|US8332020||28 Ene 2011||11 Dic 2012||Proteus Digital Health, Inc.||Two-wrist data gathering system|
|US8336545||16 Ene 2007||25 Dic 2012||Novartis Pharma Ag||Methods and systems for operating an aerosol generator|
|US8348177||15 Jun 2009||8 Ene 2013||Davicon Corporation||Liquid dispensing apparatus using a passive liquid metering method|
|US8349294||14 Dic 2010||8 Ene 2013||Novartis Ag||Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery and methods of use|
|US8371290||9 Oct 2008||12 Feb 2013||General Electric Company||Device for delivery and regulation of volatile fluids into inspiratory gas|
|US8371299||10 Abr 2008||12 Feb 2013||Respironics Respiratory Drug Delivery||Ventilator aerosol delivery|
|US8398001||19 Jun 2006||19 Mar 2013||Novartis Ag||Aperture plate and methods for its construction and use|
|US8404217||22 Jul 2005||26 Mar 2013||Novartis Ag||Formulation for pulmonary administration of antifungal agents, and associated methods of manufacture and use|
|US8419638||18 Nov 2008||16 Abr 2013||Proteus Digital Health, Inc.||Body-associated fluid transport structure evaluation devices|
|US8511581||8 Mar 2011||20 Ago 2013||Pari Pharma Gmbh||Fluid droplet production apparatus and method|
|US8539944||8 Abr 2008||24 Sep 2013||Novartis Ag||Devices and methods for nebulizing fluids for inhalation|
|US8545463||26 Ene 2007||1 Oct 2013||Optimyst Systems Inc.||Ophthalmic fluid reservoir assembly for use with an ophthalmic fluid delivery device|
|US8561604||12 Feb 2007||22 Oct 2013||Novartis Ag||Liquid dispensing apparatus and methods|
|US8578931||18 Abr 2000||12 Nov 2013||Novartis Ag||Methods and apparatus for storing chemical compounds in a portable inhaler|
|US8616195||27 Abr 2004||31 Dic 2013||Novartis Ag||Nebuliser for the production of aerosolized medication|
|US8684980||15 Jul 2011||1 Abr 2014||Corinthian Ophthalmic, Inc.||Drop generating device|
|US8709484||24 Oct 2008||29 Abr 2014||Novartis Ag||Phospholipid-based powders for drug delivery|
|US8715623||31 Oct 2007||6 May 2014||Novartis Ag||Pulmonary delivery of aminoglycoside|
|US8733343 *||29 Oct 2007||27 May 2014||Universidad De Sevilla||Device and method for creating aerosols for drug delivery|
|US8733935||15 Jul 2011||27 May 2014||Corinthian Ophthalmic, Inc.||Method and system for performing remote treatment and monitoring|
|US8877162||6 Dic 2012||4 Nov 2014||Novartis Ag||Stable metal ion-lipid powdered pharmaceutical compositions for drug delivery|
|US8936021||6 Oct 2008||20 Ene 2015||Optimyst Systems, Inc.||Ophthalmic fluid delivery system|
|US9008761||6 Nov 2012||14 Abr 2015||Proteus Digital Health, Inc.||Two-wrist data gathering system|
|US9014779||28 Ene 2011||21 Abr 2015||Proteus Digital Health, Inc.||Data gathering system|
|US9022027 *||2 May 2013||5 May 2015||Pneumoflex Systems, Llc||Nebulizer with intra-oral vibrating mesh|
|US9027548 *||17 Ene 2006||12 May 2015||Pari Pharma Gmbh||Aerosol generating device and inhalation therapy unit provided with this device|
|US9084566||6 Ene 2009||21 Jul 2015||Proteus Digital Health, Inc.||Smart parenteral administration system|
|US9087145||15 Jul 2011||21 Jul 2015||Eyenovia, Inc.||Ophthalmic drug delivery|
|US9108211||17 Abr 2006||18 Ago 2015||Nektar Therapeutics||Vibration systems and methods|
|US9125979||24 Oct 2008||8 Sep 2015||Proteus Digital Health, Inc.||Fluid transfer port information system|
|US9227029 *||2 Oct 2013||5 Ene 2016||Pneumoflex Systems, Llc||Nebulizer having horizontal venturi|
|US9421166||8 Abr 2014||23 Ago 2016||Novartis Ag||Pulmonary delivery of aminoglycoside|
|US9439862||2 Abr 2014||13 Sep 2016||Novartis Ag||Phospholipid-based powders for drug delivery|
|US20030072717 *||22 Feb 2002||17 Abr 2003||Vapotronics, Inc.||Inhalation device having an optimized air flow path|
|US20030136402 *||7 Ene 2003||24 Jul 2003||Brigham And Women's Hospital, Inc.||Method for altering the body temperature of a patient using a nebulized mist|
|US20030209243 *||19 Dic 2002||13 Nov 2003||Inhale Therapeutic Systems||Dry powder dispersing apparatus and methods for their use|
|US20030226906 *||2 May 2003||11 Dic 2003||Aerogen, Inc.||Droplet ejector with oscillating tapered aperture|
|US20040039755 *||5 Jun 2003||26 Feb 2004||Matthew Kunze||Metadata relationships|
|US20040050860 *||26 Jun 2003||18 Mar 2004||Crowder Timothy M.||Apparatus, systems and related methods for dispensing and /or evaluating dry powders|
|US20040055598 *||27 Jun 2003||25 Mar 2004||Crowder Timothy M.||Apparatus, systems and related methods for processing, dispensing and/or evaluating non-pharmaceutical dry powders|
|US20040062722 *||8 Oct 2003||1 Abr 2004||Igor Gonda||Method of use of monomeric insulin as a means for improving the reproducibilty of inhaled insulin|
|US20040089290 *||4 Nov 2003||13 May 2004||Aradigm Corporation||Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume|
|US20040139968 *||5 Ene 2004||22 Jul 2004||Aerogen, Inc.||Fluid filled ampoules and methods for their use in aerosolizers|
|US20040153262 *||26 Jun 2003||5 Ago 2004||Crowder Timothy M.||Dry powder dose filling systems and related methods|
|US20040170568 *||19 Ago 2003||2 Sep 2004||Weers Jeffry G.||Stabilized preparations for use in metered dose inhalers|
|US20040256487 *||20 May 2004||23 Dic 2004||Collins James F.||Ophthalmic drug delivery system|
|US20050034719 *||16 Oct 2002||17 Feb 2005||Franz Feiner||Inhalation therapy apparatus|
|US20050042170 *||12 Feb 2004||24 Feb 2005||The Brigham And Women's Hospital, Inc.||Method and device for generating mists and medical uses thereof|
|US20050103337 *||21 Oct 2004||19 May 2005||Anthony James Hickey||Dry powder inhalers, related blister package indexing and opening mechanisms, and associated methods of dispensing dry powder substances|
|US20050109659 *||21 Oct 2004||26 May 2005||Hickey Anthony J.||Blister packages with frames and associated methods of fabricating dry powder drug containment systems|
|US20050125002 *||1 Nov 2004||9 Jun 2005||George Baran||System and method for manipulating a catheter for delivering a substance to a body cavity|
|US20050126569 *||26 Ene 2005||16 Jun 2005||Crowder Timothy M.||Dry powder inhalers, related blister devices, and associated methods of dispensing dry powder substances and fabricating blister packages|
|US20050133024 *||24 Nov 2004||23 Jun 2005||Coifman Robert E.||Devices for measuring inspiratory airflow|
|US20050229927 *||20 Abr 2004||20 Oct 2005||Aerogen, Inc.||Ventilation systems and methods employing aerosol generators|
|US20050263608 *||9 May 2005||1 Dic 2005||Aerogen, Inc.||Droplet ejector with oscillating tapered aperture|
|US20050267628 *||12 Jul 2005||1 Dic 2005||Oriel Therapeutics, Inc.||Dry powder dose filling systems and related methods|
|US20050274377 *||17 May 2005||15 Dic 2005||Igor Gonda||Method of treating diabetes mellitus in a patient|
|US20050279349 *||24 Oct 2003||22 Dic 2005||Patton John S||Method and device for delivering aerosolized medicaments|
|US20050279851 *||6 Jun 2005||22 Dic 2005||Aerogen, Inc.||Method and apparatus for dispensing liquids as an atomized spray|
|US20060001952 *||7 Jul 2004||5 Ene 2006||Liekki Oy||Method and device for producing optical material, and an optical waveguide|
|US20060093556 *||21 Nov 2005||4 May 2006||Aradigm Corporation||Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin|
|US20060097068 *||31 Jul 2003||11 May 2006||Markus Urich||Fluid droplet production apparatus and method|
|US20060102172 *||30 Oct 2003||18 May 2006||Pari Gmbh Spezialisten Fur Effektive Inhalation||Inhalation therapy device|
|US20060124125 *||31 Ene 2006||15 Jun 2006||Igor Gonda||Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume|
|US20060164912 *||15 Oct 2003||27 Jul 2006||Christophe Arnaud||Method and device for making a dispersion or an emulsion|
|US20060237090 *||11 Mar 2004||26 Oct 2006||Prolitec, S.A.||Method and device for nebulisation|
|US20070023547 *||19 Jun 2006||1 Feb 2007||Aerogen, Inc.||Aperture plate and methods for its construction and use|
|US20070075161 *||18 Sep 2006||5 Abr 2007||Aerogen, Inc.||Droplet Ejector With Oscillating Tapered Aperture|
|US20070102533 *||22 Dic 2006||10 May 2007||Aradigm Corporation; Universidad De Sevilla||Aerosol created by directed flow of fluids and devices and methods for producing same|
|US20070176017 *||30 Ene 2006||2 Ago 2007||Berger Harvey L||Ultrasonic atomizing nozzle and method|
|US20070209659 *||12 Feb 2007||13 Sep 2007||Aerogen, Inc.||Liquid dispensing apparatus and methods|
|US20070256684 *||8 Mar 2007||8 Nov 2007||Aradigm Corporation||Nozzle pore configuration for intrapulmonary delivery of aerosolized formulations|
|US20080053431 *||29 Oct 2007||6 Mar 2008||The Universidad De Sevilla||Device and method for creating aerosols for drug delivery|
|US20080053436 *||30 Oct 2007||6 Mar 2008||Aradigm Corporation||Aerosol created by directed flow of fluids and devices and methods for producing same|
|US20080099010 *||25 Oct 2007||1 May 2008||Igor Gonda||Method of use of monomeric insulin as a means for improving the reproducibility of inhaled insulin|
|US20080099011 *||26 Oct 2007||1 May 2008||Novo Nordisk||Inhaled insulin dosage control delivery enhanced by controlling total inhaled volume|
|US20080197044 *||25 Abr 2008||21 Ago 2008||Oriel Therapeutics, Inc.||Blister packages with frames for dry powder drug containment|
|US20080230058 *||21 Mar 2008||25 Sep 2008||Nektar Therapeutics||Dry powder dispersing apparatus and methods for their use|
|US20080257337 *||10 Abr 2008||23 Oct 2008||Denyer Jonathan S H||Ventilator Aerosol Delivery|
|US20080264416 *||2 Jul 2008||30 Oct 2008||Novo Nordisk A/S||Method of Treating Diabetes Mellitus in a Patient|
|US20080308096 *||17 Ene 2006||18 Dic 2008||Pari Pharma Gmbh||Aerosol Generating Device and Inhalation Therapy Unit Provided with This Device|
|US20090022669 *||20 Jun 2008||22 Ene 2009||Vapotronics, Inc.||Compositions for protein delivery via the pulmonary route|
|US20090107503 *||22 Oct 2008||30 Abr 2009||Trudell Medical Limited||Nebulizing catheter system and methods of use and manufacture|
|US20090173341 *||13 Mar 2009||9 Jul 2009||Injet Digital Aerosols Limited||Inhalation device having an optimized air flow path|
|US20090241950 *||12 May 2009||1 Oct 2009||Aradigm Corporation||Method of treating diabetes mellitus in a patient|
|US20090288659 *||13 May 2009||26 Nov 2009||Heikki Haveri||Apparatus, system and method for administering an anesthetic agent for a subject breathing|
|US20090308945 *||15 Jun 2009||17 Dic 2009||Jacob Loverich||Liquid dispensing apparatus using a passive liquid metering method|
|US20110155768 *||8 Mar 2011||30 Jun 2011||Pari Pharma Gmbh||Fluid droplet production apparatus and method|
|US20120318259 *||12 Ene 2011||20 Dic 2012||Omega Life Science Ltd.||Method and apparatus for producing fine concentrated aerosol|
|US20130108748 *||31 Oct 2012||2 May 2013||Pepsico., Inc.||Dispensing Nozzle with an Ultrasound Activator|
|US20130267864 *||2 May 2013||10 Oct 2013||Pneumoflex Systems, Llc||Nebulizer with intra-oral vibrating mesh|
|US20140034051 *||2 Oct 2013||6 Feb 2014||Pneumoflex Systems, Llc||Nebulizer having horizontal venturi|
|US20140053835 *||15 Feb 2013||27 Feb 2014||Capnia, Inc.||Gas dispenser with diffusing nosepiece|
|US20140110500 *||16 May 2012||24 Abr 2014||The Technology Partnership Plc.||Separable membrane improvements|
|DE4300880A1 *||15 Ene 1993||21 Jul 1994||Draegerwerk Ag||Ultraschallvernebler mit Dosiereinheit|
|EP0156409A2 *||18 Feb 1985||2 Oct 1985||Jean Michel Anthony||Device for moistening parts of the human body|
|EP0156409A3 *||18 Feb 1985||25 Jun 1986||Jean Michel Anthony||Device for moistening parts of the human body|
|EP0186280A2 *||25 Oct 1985||2 Jul 1986||Robert Landis||Breath activated medication spray|
|EP0186280A3 *||25 Oct 1985||13 Ene 1988||Robert Landis||Breath activated medication spray|
|EP0200258A2 *||17 Abr 1986||5 Nov 1986||Jean Michel Anthony||Ultrasonic spraying device|
|EP0200258A3 *||17 Abr 1986||3 Feb 1988||Jean Michel Anthony||Ultrasonic spraying device|
|EP0232235A2 *||23 Ene 1987||12 Ago 1987||A/S GEA Farmaceutisk Fabrik||Medical dosing device for discharge of atomized medicament for inhalation air|
|EP0642802A2 *||5 Ago 1994||15 Mar 1995||Disetronic Ag||Inhalation device|
|EP0844027A1 *||5 Ago 1996||27 May 1998||Omron Corporation||Atomization apparatus and method utilizing surface acoustic waves|
|EP1066850A1 *||28 Abr 2000||10 Ene 2001||Siemens Elema AB||Medical Nebulizer|
|EP1219313A1||29 Dic 2000||3 Jul 2002||Instrumentarium Corporation||Liquid discharging apparatus and magneto-shape-memory type valve|
|EP1219314A1||29 Dic 2000||3 Jul 2002||Instrumentarium Corporation||Liquid discharge apparatus having magnetic valve|
|EP1227856A1 *||27 Oct 2000||7 Ago 2002||PARI GmbH Spezialisten für effektive Inhalation||Inhalation nebulizer|
|EP1310268A2 *||10 Jul 1995||14 May 2003||Aradigm Corporation||Intrapulmonary drug delivery within therapeutically relevant inspiratory flow/volume values|
|EP1694392A2 *||24 Nov 2004||30 Ago 2006||Robert E. Coifman||Devices for measuring inspiratory airflow|
|EP2050478A1 *||16 Oct 2007||22 Abr 2009||GE Healthcare Finland Oy||Device for delivery and regulation of volatile fluids into inspiratory gas|
|EP2050479A2 *||20 May 2008||22 Abr 2009||General Electric Company||Apparatus, system and method for admistering an anesthetic agent for a subject breathing|
|EP2119465A1 *||16 May 2008||18 Nov 2009||Markos Mefar S.P.A.||Nebulizer with breathing phase detecting sensor for delivering nebulized drugs to a user|
|WO1989006147A1 *||27 Oct 1988||13 Jul 1989||Etelä-Hämeen Keuhkovammayhdistys R.Y.||Ultrasonic atomizer|
|WO1992011050A1 *||17 Dic 1991||9 Jul 1992||Minnesota Mining And Manufacturing Company||Inhaler|
|WO1992011512A1 *||17 Dic 1991||9 Jul 1992||Minnesota Mining And Manufacturing Company||Device for measuring a pre-determined volume of liquid flowing there through|
|WO1996001663A1 *||10 Jul 1995||25 Ene 1996||Aradigm Corporation||Intrapulmonary drug delivery within therapeutically relevant inspiratory flow/volume values|
|WO1996013290A1 *||27 Oct 1995||9 May 1996||Aradigm Corporation||Device for aerosolized delivery of peptide drugs|
|WO1996013291A1 *||27 Oct 1995||9 May 1996||Aradigm Corporation||Device for aerosolizing narcotics|
|WO1996013292A1 *||27 Oct 1995||9 May 1996||Aradigm Corporation||Device and method of creating aerosolized mist of respiratory drug|
|WO1996028205A1 *||14 Mar 1996||19 Sep 1996||Siemens Aktiengesellschaft||Ultrasonic atomizer device with removable precision dosing unit|
|WO1996028206A1 *||14 Mar 1996||19 Sep 1996||Siemens Aktiengesellschaft||Ultrasonic atomizer device with removable precision dosating unit|
|WO1996030068A1 *||15 Mar 1996||3 Oct 1996||Aradigm Corporation||Intrapulmonary delivery of hematopoietic drug|
|WO1996031289A1||3 Abr 1996||10 Oct 1996||Fluid Propulsion Technologies, Inc.||Methods and apparatus for dispensing liquids as an atomized spray|
|WO1997018846A1 *||18 Nov 1996||29 May 1997||R + D Injector Ag||Nebulizing device|
|WO1997031721A1 *||27 Feb 1997||4 Sep 1997||Medix Limited||A nebuliser|
|WO2001019437A1||8 Sep 2000||22 Mar 2001||Instrumentarium Corporation||Nebulizer apparatus|
|WO2001032246A1 *||3 Nov 2000||10 May 2001||Pari GmbH Spezialisten für effektive Inhalation||Inhalation nebuliser|
|WO2001076762A2||4 Abr 2001||18 Oct 2001||Instrumentarium Corporation||Method of maximizing the mechanical displacement of a piezoelectric nebulizer apparatus|
|WO2002036269A1||12 Oct 2001||10 May 2002||Instrumentarium Corporation||Device and method for detecting and controlling liquid supply to an apparatus discharging liquid|
|WO2002087772A1 *||1 May 2002||7 Nov 2002||Aerogen, Inc.||Cymbal-shaped actuator for a nebulizing element|
|WO2003059423A1 *||15 Ene 2003||24 Jul 2003||Aerogen, Inc.||Systems and methods for clearing aerosols from the effective anatomic dead space|
|WO2005011574A2 *||23 Jul 2004||10 Feb 2005||Coifman Robert E||Microporous membrane nebulizers|
|WO2005011574A3 *||23 Jul 2004||20 Oct 2005||Robert E Coifman||Microporous membrane nebulizers|
|WO2005051177A3 *||24 Nov 2004||16 Mar 2006||Robert E Coifman||Devices for measuring inspiratory airflow|
|WO2005102431A3 *||20 Abr 2005||22 Jun 2006||Aerogen Inc||Aerosol delivery apparatus for pressure assisted breathing|
|WO2007106386A2||9 Mar 2007||20 Sep 2007||Aradgim Corporation||Nozzle pore configuration for intrapulmonary delivery of aerosolized formulations|
|WO2012156724A2||16 May 2012||22 Nov 2012||The Technology Partnership Plc||Separable membrane improvements|
|Clasificación de EE.UU.||128/200.16, 239/102.2|
|Clasificación internacional||B05B17/06, A61M15/00, A61M11/00|
|Clasificación cooperativa||B05B17/063, B05B17/0623, A61M15/0085, A61M2011/001|
|Clasificación europea||B05B17/06B2B, A61M15/00F, B05B17/06B2|