US3387607A - Apparatus for inhalation therapy - Google Patents

Apparatus for inhalation therapy Download PDF

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US3387607A
US3387607A US626319A US62631967A US3387607A US 3387607 A US3387607 A US 3387607A US 626319 A US626319 A US 626319A US 62631967 A US62631967 A US 62631967A US 3387607 A US3387607 A US 3387607A
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liquid
transducer
aerosol
chamber
medicament
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US626319A
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William D Gauthier
Flora Robert J Della
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DeVilbiss Co
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DeVilbiss Co
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M15/00Inhalators
    • A61M15/0085Inhalators using ultrasonics
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05BSPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B05B17/06Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
    • B05B17/0607Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
    • B05B17/0615Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers spray being produced at the free surface of the liquid or other fluent material in a container and subjected to the vibrations
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B05SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05BSPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B05B17/06Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
    • B05B17/0607Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
    • B05B17/0638Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers spray being produced by discharging the liquid or other fluent material through a plate comprising a plurality of orifices
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S261/00Gas and liquid contact apparatus
    • Y10S261/48Sonic vibrators
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S261/00Gas and liquid contact apparatus
    • Y10S261/65Vaporizers

Definitions

  • inhalation therapy is carried out by the steam vaporization of water or water-borne medicaments or by mechanically nebulizing water or other appropriate medicaments.
  • the mechanical nebulizers presently used disperse the liquid into an air-suspended fog of small particles pneumatically.
  • the nebulization is characterized by a random particle size so that the air-suspended mass of droplets contains many large particles that will settle out and will not be inhaled and only a relatively small percentage of particles or droplets small enough to actually reach the affected portions of the respiratory tract in such condition that the treatment is effective. It is generally believed that if the droplets in the fog are greater in diameter than about 6 microns, they will not enter the lungs or lower respiratory tract satisfactorily but may settle out or condense, according to the literature.
  • the nebulizer of the present invention delivers a true aerosol which may be discharged into the open air in front of the patient so that he inhales a mixture of air and nebulized liquid, or the apparatus may be used to deliver the aerosol through a tube terminating in a mask which is placed over the nose and mouth of the patient.
  • the density of the aerosol or fog of inhaled liquid particles can be made as high as the physician requires and can be controlled.
  • a slight positive pressure can be maintained at the mask to relieve the patient from the labor of inhalation and to insure complete entry of the nebulized medicine into the desired regions of the respiratory tract.
  • present devices When the nebulized liquid is delivered into the room, present devices are found to be inefiicient and of such low capacity that several of them may be required to deliver the desired quantity of aerosolized fluid and the resulting aerosol density is very low.
  • a single conventional air operated nebulizer unit will deliver about 750 cubic centimeters of liquid per day but an appreciable percentage of the particles in the discharge are of a size range that is not usable for treatment by inhalation.
  • the unit of the present invention will nebulize in excess of 7500 cubic centimeters per day, and a much greater percentage of the aerosolized fluid will be of a particle size appropriate for reaching the desired portions of the respiratory tract.
  • One of the objects of the present invention is to increase the capacity of nebulizing units and to deliver a high volume and dense mass of nebulized fluid having a particle size suitable for inhalation therapy not 3,387,607 Patented June 11, 1968 only in the upper respiratory tract but in the lungs themselves.
  • Another object of the invention is to provide an ultrasonic nebulizer in which the acoustic power density at the surface of the liquid being nebulized is maintained within an optimum range between a low value at which insufficient nebulization takes place and a high value in which the acoustic energy is expended in the formation of a high, thin geyser from which little of the liquid passes into a nebulized form, within the particle size range that will penetrate by inhalation into the human respiratory tract.
  • Another object of the present invention is to provide an apparatus in which a greater percentage of the medicament particles are within a narrow range of sizes that will effectively penetrate the respiratory tract by inhalation and that will not be re-breathed.
  • An advantage of the present invention is that there is no substantial change in the concentration of additives in the medicament as occurs with mechanically operated nebulizers which tend to evaporate the more readily vaporizable fractions of the liquid throughout the course of the treatment.
  • Still another advantage of the present invention is the absence of the objectionable and disturbing noise that accompanies the operation of conventional mechanical nebulizers, and the absence of added heat that accompanies the use of steam Vaporizers.
  • the word medicament is broad enough to include any substance that has a therapeutic effect, and for many disorders, water is such a substance.
  • many of the medicines required for inhalation therapy are expensive and are required only in small amounts.
  • the capacity of the units constructed in accordance with the present invention is high, the arrangement of the parts is such that effective nebulization of very small quantities of liquid is obtainable.
  • the energy required to break up the liquid into droplets is derived, in the present invention, by directing ultrasonic compressional wave energy through. a body of coupling liquid into a treatment or nebulizing chamber.
  • the nebulizing chamber is removable from the portion of the apparatus containing the sound transducer and coupling liquid so that it may be removed therefrom and autoclaved if desired.
  • the sound energy is passed through an acoustically transparent spherically curved Window in the bottom wall of the nebulizing chamber, and into the body of liquid in the nebulizing chamber.
  • the geyser is quite violent but very little of the liquid is dispersed into droplets in the size range that is effective for inhalation therapy, or in the size range between 1 and 6 microns in diameter.
  • Proper power density can also be achieved by applying a relatively high electrical power per unit of active surface of non-focusing electro-acoustical transducers.
  • a nonviolent geyser with a broad base occurs, and the shape of that geyser is such that sonic reflections from the generally parabolic surface of the geyser effects a concentration of the sonic energy probably within the geyser itself to give optimum nebulization.
  • maintaining the proper power density range over a larger area increases aerosol production.
  • the proper acoustical power density can also be obtained by slightly detuning the unit from a frequency which would give a violent geyser with a given transducer and thus decreasing the electro-acoustical transducers efficiency.
  • This method of power density control can, however, reflect in undue heating of the equipment.
  • the apparatus of the present invention is primarily intended for nebulizing fluids for inhalation therapy, it has also been found to be effective for emulsifying immiscible liquids in small quantities, for example, in those cases where an extremely expensive materiat must be suspended in an inexpensive carrier. It has also been found to be useful in producing a fog of antiseptic materials for room sterilization because the small particle size of the aerosol has substantially enhanced penetrating power.
  • the primary object of the present invention is to provide a new method of forming an aerosol of a liquid suitable for inhalation therapy, which method is characterized by the creation of a large volume of aerosol particles by means of ultrasonic energy focused within the geyser ultrasonically formed on the surface of the treatment liquid.
  • FIG. 1 is a diagrammatic view, with parts in section and parts broken away of an apparatus constructed in accordance with the present invention and arranged to carry out the method thereof;
  • FIG. 2 is a somewhat enlarged, central vertical sectional view, of a portion of the apparatus in which medicament nebulizing is accomplished;
  • FIG. 3 is a sectional view on line 33 of FIG. 2;
  • FIG. 4 is a detail cross-sectional view of a member, the center portion of which constitutes an acoustically transparent diaphragm and that forms a portion of the lower wall of the medicament chamber;
  • FIG. 5 is a central vertical sectional view of the preferred form of electro-acoustic transducer, with the electrode layers thereof being exaggerated in thickness;
  • FIG. 6 is a fragmentary cross-sectional view of a nebulizer having a modified form of electro-acoustic transducer
  • FIG. 7 is a fragmentary cross-sectional view of a nebulizer having still another modified form of electroacoustic transducer.
  • an apparatus embodying the present invention comprises a lower housing 10 in which an electro-acoustical transducer is mounted, the transducer being in the form of a spherically curved piezoelectric crystal or crystalline mass such as a lead zirconate titanate ceramic 12, excited in the thickness mode from a suitable oscillator '14, and transmitting into a body of coupling liquid 15 which is contained in a chamber 16.
  • the chamber 16 is preferably an open top vessel having a flanged extension 18 and a pouring lip 19 so that it can be conveniently emptied when necessary.
  • the transducer 12 has an electrically conductive coating on its front face that extends over the edges of the spherical body onto the rear surface thereof, which coating forms a ground electrode 20 of the energizing circuit. Spaced inwardly from the electrode 20 formed by the above-described coating, and separated therefrom by an annular band of the insulating ceramic material of the transducer is an electrode 21 which is connected to one side of the oscillator 14 through a spring contact 21w. Thus both electrical connections to the transducer are made on the rear face thereof and away from the face that is in contact with the coupling liquid.
  • the resonant frequency of operation depends, of course, on the material and physical dimensions of the transducer and on its mounting.
  • the transducer 12 is preferably a spherically ground body of lead zirconate titanate ceramic, polarized in the direction of its thickness, although a fiat transducer similarly polarized may be used as hereinafter described.
  • a resonant frequency of 1.25 megacycles per second has been found to be satisfactory although higher or lower frequencies in the ultrasonic rangemay be used.
  • a transducer resonating at 1.25 megacycles per second is more rugged and less expensive than one operating at higher frequencies.
  • the transducer is mounted in position in the bottom of the chamber 16 against an O-ring 22.
  • a follower ring 23 contacts the underface of the crystal 12 adjacent its edges and is in electrical contact with the annular ground electrode 20, and the follower ring is urged against the transducer by a plurality, preferably three, of coil springs 24 disposed between the follower ring 23 and the bottom of the housing 16.
  • the ground electrode 20' is thus connected to the oscillator 14 by the follower ring, the springs 24 and a suitable conductor.
  • the nebulizing chamber comprises a vessel 26 carried on a lower ring 27 and removably supported by suitable legs 28 on the flange surface 18 of the lower chamber or housing 16.
  • a transparent cover is preferably used to close and seal the open upper end of the vessel.
  • the bottom surface of the vessel 26 includes a downwardly tapered wall 29 having a central opening 30, and 21 diaphragm 31 is clamped against the wall 30 by an annular clamp ring 32.
  • the diaphragm 3-1 is made of a thin acoustically transparent plastic membrane such as Mylar and has a center portion that is molded into a central downwardly extending spherically curved window 33.
  • the Mylar diaphragm need be only two or three thousandths of an inch thick; enough to be self-sustaining and sufficiently rugged to withstand normal handling. A pierced or broken diaphragm can be easily replaced by removing the clamp ring 32.
  • the spherically curved window 33 has the additional advantage that it permits small amounts of liquid on its concave upper surface to be subjected to the sound transmission and concentrated in the center area where the acoustical energy is of the desired density.
  • the level of liquid within the nebulizing chamber may be maintained at a preselected level by any suitable automatic means.
  • a simple float operated valve including a toroidally shaped float 40 pivotally connected to a needle valve 41 by a lever fulcrumed at 42 may be used to control the opening of a supply line 43.
  • this supply line comprises a tubular inlet pipe connected at its upper end to a supply conduit 44 and fixed adjacent the wall of the nebulizing chamberby a connector 45.
  • the supply conduit 44 in turn connects to a jar of the liquid which it is desired to nebulize flow to the nebulizer being caused by gravity.
  • the float causes the needle valve 41 to open, and when the level has risen to the preselected point, the float closes the inlet supply valve.
  • the energy radiated from the transducer 12 to the liquid ini the nebulizing chamber 16 causes the liquid to be thrown upward in the nebulizing chamber.
  • the geyser By establlshing a relatively Wide zone of application of the acoustic energy to the surface of the liquid, the geyser is lower and the-output of suitable aerosol is increased.
  • a sharply focused beam of sonic energy produces a violent, high geyser butvirtually no aerosol.
  • the size of the resulting droplets will vary inversely with the frequency of operation, a higher frequency causing the appearance of smaller droplets. For inhalation therapy droplets between about 1 micron and about 6 microns are believed to be desirable.
  • the droplets are so fine that many of them are rebreathedjI-and are less effective for treatment.
  • the-droplets exhibit a pronounced tendency to settle out and not all of the liquid will enter the respiratory tract of the patient and very little of the liquid will enter the lungs for deep therapy.
  • the droplet size appears to be optimum, very little of the liquid being re-breathed and very little of it settling out even though the aerosol may be transmitted through several feet of tubing from the nebulizer to the patient.
  • One form of the present invention provides a motor driven blower 50 which causes a current of carrier gas to pass.th'rough the nebulizing chamber and forces the nebulized particles through a discharge fitting 51 and into a conveying tube 52.
  • a settling trap in the form of an upwardly extending arm 53 having a cover 54 is provided to separate any large droplets that might have been carried away with the desired aerosol or finely nebulized material.
  • nebulizer of the present invention may be so operated if the blower 50 is turned off or not used.
  • Nebulizers are frequently used unattended, and there is the possibility that the supply of liquid to the nebulizing chamber may become exhausted. If this happens, the continued operation of the transducer 12 might burn the thin window 33 and puncture it. It is therefore desirable to control the operation of the transducer thermostatically in accordance with the attained temperature of the lower vessel 16 which reflects the temperature of the coupling liquid 15.
  • a thermostat T is shown diagrammatically in FIG. 2 in position to accomplish this control. If the coupling liquid becomes too hot, the transducer should be turned off not only to save the window 33 but to save the transducer itself since some transducer materials are not capable of withstanding temperatures in excess of C. without depolarization, and the coupling liquid is relied on to cool the transducer.
  • the coupling liquid container 16 is filled with water which, as above noted, need not be de-gassed.
  • the previously sterilized nebulizing chamber or vessel 26 is placed on the flanged surface of the lower housing and connections to the medicament jar are made through conduit 44 and connections to the blower 50 and to the discharge tube 52 are likewise established. These connections may be simply frictional connections between a flexible tube and the appropriate fittings on the vessel 26.
  • the nebulizing vessel 16 will fill promptly from its supply jar until the float controlled valve 41 is closed by its float.
  • the oscillator 14 may then be turned on and the nebulizing chamber will immediately fill with a dense mass of very finely divided or air-borne nebulized liquid.
  • the blower 50 will operate to convey the aerosol from the nebuilizing chamber through the discharge tube 52 to the patient.
  • the oscillator 14 is initially adjusted to the resonant frequency of the transducer 12 and is then de-tuned to drive the transducer at a frequency above its resonant frequency.
  • a transducer having a designed resonant frequency of 1.25 megacycles per second operates to produce a maximum volume of aerosol when driven at about 1.35 megacycles per second.
  • the adjustment of the oscillator can be made visually because the aerosol output in the vessel 26 is noticeably affected by a change in frequency of the oscillator and thus of the transducer 12.
  • the appearance of a dense fog of nebulized material accompanying a low, broad geyser is indicative of satisfactory adjustment.
  • the operation of the blower 50 may be adjusted to increase or decrease the throughput of air or carrier gas and thus increase or decrease the quantity and density of aerosol supplied to the patient and, if desired, the positive pressure created by the blower may be dispensed with and the vessel 26 used as a supply of aerosol to be drawn therefrom on demand by the patient.
  • Controlling the quantity and density of the aerosol supplied to the patient from the apparatus of the present invention is desirable, because the peak aerosol density that is obtainable is much greater than can be initially tolerated by the patient in some instances.
  • the attending physician will cause the patient to breathe a relatively dilute aerosol solution and then increase its density gradually until the desired density of the unit is reached. If the full density were to be used at the beginning of the treatment, certain results of the treatment might be lost because of the inability of the patient to tolerate the high density aerosol without coughing or otherwise refusing to inhale the medicament.
  • the diaphragm 31 may be dispensed with and the liquid that has been previously denoted as a coupling liquid may become the nebulized material.
  • a float controlled valve will be used to maintain the level of liquid substantially constant but there will be no separation of the medicament and coupling liquids as such, these two liquids being, in this case, the same.
  • FIG. 6 shows a portion of a nebulizer having a modified form of the transducer system.
  • the transducer mass is a flat-ground plate 120 of piezoelectric material which will radiate plane-parallel waves into the coupling liquid.
  • An acoustic lens 121 is provided which may comprise a double concave body of Lucite or polystyrene resin having a central orifice 122 to allow the circulation of coupling liquid.
  • the electrical energy is brought into the plate 120 by a peripheral electrode 123 which extends across the front of the transducer and around to the margin of the rear face, and by the central electrode 124 which is confined to the rear face as in the form shown in FIG. 2. Contact to these electrodes from the oscillator are made as previously described.
  • the ultrasonic energy orginating in the transducer is focused by the lens 121, and the focal point is well above the medicament chamber as before.
  • the operation is the same as previously described except for the arrangement by which a focused beam of ultrasonic energy is caused to pass through the coupling liquid into the medicament chamber.
  • FIG. 7 shows an alternate form in which a flat transducer is used, the transducer itself being designated by the reference number 140'. Power is supplied thereto through connectors 141 and 142. The transducer 140 vibrates to project its compressional wave energy upwardly through the liquid to the surface thereof where a broad, dome-like geyser is formed. The sound waves appear to come to a focus within the geyser by reflection from the air-liquid interface to form a high concentration of suitably nebulized liquid as indicated at 143 in FIG. 7.
  • the proper level of ultrasonic power density at the surface of the liquid is not achieved by a focusing electro-acoustical transducer through a coupling liquid or by a focusing system located below the normal liquid level, but rather is obtained by exciting a nonfocusing transducer by a much higher power density than is applied to the transducer in a focusing system. Since the focusing is achieved within the geyser itself when proper power density is applied at the liquid surface, the liquid level is not critical and a liquid-level control means is not required.
  • nebulization can be effected if 1.35 mc. electrical power is applied in a range from approximately 20 to approximately 100 watts. Approximately the same power density at the normal surface level could be obtained by applying the same power to a flat transducer with a diameter of approximately 1".
  • FIGS. 2, 6 and 7 show diagrammatically the broadbased geyser in which concentration of the sonic energy occurs, probably by reflection from the Walls of the geyser itself.
  • concentration of the sonic energy occurs, probably by reflection from the Walls of the geyser itself.
  • Such a geyser has been found to be most effective, but in practice it is diflicult to make a precise examination of the geyser because of the presence of the dense aerosol or fog within the chamber 26. Attempting to blow the fog away to examine the geyser probably results in distorting the configuration thereof.
  • an apparatus for creating an aerosol for medical purposes the combination of, means forming a chamber for containing an acoustic coupling liquid, a body of coupling liquid in said chamber, an electro-acoustic-transducer system, said transducer system having a transducer forming at least a portion of a lower wall of said chamber and so constructed and arranged that when energized beams of ultrasonic energy pass through said coupling liquid, a separable medicament chamber disposed over said coupling liquid chamber and having an acoustically transparent lower wall immersed in said coupling liquid, means to control the level of liquid medicament in.
  • said medicament chamber the focal point of said transducer system being within said medicament chamber but above the level of liquid medicament therein, said beams of sonic energy intersecting the surface of said medicament liquid in a broad zone, means to energize said transducer system at a power density per unit of transducer area that will cause violent agitation and cavitation of the surface of said liquid medicament and said beams of sonic energy come to a focus within a geyser thrown upwardly therefrom, whereby to cause the dispersal of said liquid medicament into an aerosol of medicament droplets, and means to remove said aerosol from said medicament chamber.
  • an electro-acoustic transducer system having a transducer forming at least a portion of the bottom wall of said chamber and so constructed and arranged that when energized beams of ultrasonic energy pass through said body of liquid, a nebulizing chamber disposed over said first chamber, said beams of ultrasonic energy intersectg ing the surface of liquid to b nebuilized in said nebulizing chamber in a broad zone, means to energize said transducer system at a power density per unit of transducer area that will cause violent agitation and cavitation of the surface of the liquid in said nebulizing chairiber, whereby said beams of ultrasonic energy come:to a focus within a geyser thrown upwardly therefrom to cause dispersal of said liquid into an aerosol, and means to remove said aerosol from said ne
  • an apparatus for creating an aerosol for medical purposes the combination of, ⁇ means forming a chamber for containing an acoustic coupling liquid, a body of coupling liquid in said chamber, an electro-acoustic transducer system, said transducer system having a transducer forming at least a portion of a lower wall of said chamber and so constructed and arranged that when energized beams of ultrasonic energy pass through said coupling liquid, a separable medicament chamber disposed over said coupling liquid chamber and having an acoustically transparent lower wall immersed in said coupling liquid, said beams of sonic energy intersecting the surface of said medicament liquid in a broad zone, means to energize said transducer system at a power density per unit of transducer area that will cause violent agitation and cavitation of the surface of said liquid medicament and said beams of sonic energy come to a focus within a geyser thrown upwardly therefrom, whereby to cause the dispersal of said liquid medicament into an aerosol of medicament

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Description

June 1968 w. D. GAUTHIER ETAL 3,337,607
APPARATUS FOR INHALATION THERAPY Filed March 27, 1967 2 Sheets-Sheet 2 OSCILLATOR INVENTORS: MLLIAM l7. EAUTHIER 022122" J 17mm 2): DEA
ATTYE.
United States Patent 3,387,607 APPARATUS FOR INHALATION THERAPY William D. Gauthier, Sylvania Township, Lucas County,
and Robert J. Della Flora, Toledo, Ohio, assignors to The De Vilbiss Company, Toledo, Ohio, a corporation of Ohio Continuation-impart of application Ser. No. 343,617,
Feb. 10, 1964. This application Mar. 27, 1967, Ser.
14 Claims. (Cl. 128173) ABSTRACT OF THE DISCLOSURE Ultrasonic apparatus for the production of an aerosol for human inhalation therapy. The aerosol is characterized by a relatively narrow range of particle size. The sonic energy is directed to produce a zone of disturbance at the surface of the liquid to be nebulized for maximum aerosol emission.
This application is a continuation-in-part of our application Ser. No. 343,617, filed Feb. 10, 1964, now abancloned.
Background of the invention At the present time inhalation therapy is carried out by the steam vaporization of water or water-borne medicaments or by mechanically nebulizing water or other appropriate medicaments. The mechanical nebulizers presently used disperse the liquid into an air-suspended fog of small particles pneumatically. The nebulization is characterized by a random particle size so that the air-suspended mass of droplets contains many large particles that will settle out and will not be inhaled and only a relatively small percentage of particles or droplets small enough to actually reach the affected portions of the respiratory tract in such condition that the treatment is effective. It is generally believed that if the droplets in the fog are greater in diameter than about 6 microns, they will not enter the lungs or lower respiratory tract satisfactorily but may settle out or condense, according to the literature.
The nebulizer of the present invention delivers a true aerosol which may be discharged into the open air in front of the patient so that he inhales a mixture of air and nebulized liquid, or the apparatus may be used to deliver the aerosol through a tube terminating in a mask which is placed over the nose and mouth of the patient. By this latter apparatus the density of the aerosol or fog of inhaled liquid particles can be made as high as the physician requires and can be controlled. If desired, a slight positive pressure can be maintained at the mask to relieve the patient from the labor of inhalation and to insure complete entry of the nebulized medicine into the desired regions of the respiratory tract. When the nebulized liquid is delivered into the room, present devices are found to be inefiicient and of such low capacity that several of them may be required to deliver the desired quantity of aerosolized fluid and the resulting aerosol density is very low. A single conventional air operated nebulizer unit will deliver about 750 cubic centimeters of liquid per day but an appreciable percentage of the particles in the discharge are of a size range that is not usable for treatment by inhalation. The unit of the present invention will nebulize in excess of 7500 cubic centimeters per day, and a much greater percentage of the aerosolized fluid will be of a particle size appropriate for reaching the desired portions of the respiratory tract.
One of the objects of the present invention, therefore, is to increase the capacity of nebulizing units and to deliver a high volume and dense mass of nebulized fluid having a particle size suitable for inhalation therapy not 3,387,607 Patented June 11, 1968 only in the upper respiratory tract but in the lungs themselves.
Another object of the invention is to provide an ultrasonic nebulizer in which the acoustic power density at the surface of the liquid being nebulized is maintained within an optimum range between a low value at which insufficient nebulization takes place and a high value in which the acoustic energy is expended in the formation of a high, thin geyser from which little of the liquid passes into a nebulized form, within the particle size range that will penetrate by inhalation into the human respiratory tract.
Another object of the present invention is to provide an apparatus in which a greater percentage of the medicament particles are within a narrow range of sizes that will effectively penetrate the respiratory tract by inhalation and that will not be re-breathed.
An advantage of the present invention is that there is no substantial change in the concentration of additives in the medicament as occurs with mechanically operated nebulizers which tend to evaporate the more readily vaporizable fractions of the liquid throughout the course of the treatment.
Still another advantage of the present invention is the absence of the objectionable and disturbing noise that accompanies the operation of conventional mechanical nebulizers, and the absence of added heat that accompanies the use of steam Vaporizers.
As herein used, the word medicament is broad enough to include any substance that has a therapeutic effect, and for many disorders, water is such a substance. However, many of the medicines required for inhalation therapy are expensive and are required only in small amounts. While the capacity of the units constructed in accordance with the present invention is high, the arrangement of the parts is such that effective nebulization of very small quantities of liquid is obtainable.
The energy required to break up the liquid into droplets is derived, in the present invention, by directing ultrasonic compressional wave energy through. a body of coupling liquid into a treatment or nebulizing chamber. The nebulizing chamber is removable from the portion of the apparatus containing the sound transducer and coupling liquid so that it may be removed therefrom and autoclaved if desired. The sound energy is passed through an acoustically transparent spherically curved Window in the bottom wall of the nebulizing chamber, and into the body of liquid in the nebulizing chamber.
It has long been known that a focused beam of ultrasonic compressional wave energy can be used to cause violent cavitation of the surface of a body of liquid causing what is referred to in the literature as a geyser. This violent surface activity throws liquid upwardly from the surface of the mass, but does not disperse an appreciable amount of it into small particles as would be expected. We have found that creation of a dense fog of liquid particles having a size range suitable for inhalation therapy is best obtained when the geyser is low and broad, having a dome-like configuration as hereinafter explained.
We have found that if the focusing of the sound beam is sharp and the focal point occurs at or very near the liquid surface the energy is expended in the formation of the violent and high geyser and not in the production of the desired aerosol. However, if the acoustic power density at the liquid surface is controlled properly the geyser can be quite broad and low, but the quantity of aerosol can be greatly increased. Optimizing this power density can be achieved in several ways: by focusing the sound waves well above or (less favorably) well below the liquid surface, by utilizing a flat transducer, by utilizing a relatively poorly focusing transducer or by driving a transducer at a frequency different than, preferably above, its resonant frequency. If the ultrasonic energy is focused at or near the surface of the liquid and appreciable power is applied the geyser is quite violent but very little of the liquid is dispersed into droplets in the size range that is effective for inhalation therapy, or in the size range between 1 and 6 microns in diameter.
Proper power density can also be achieved by applying a relatively high electrical power per unit of active surface of non-focusing electro-acoustical transducers. When the proper range of sonic power density occurs at the surface of the liquid, it has been found that a nonviolent geyser with a broad base occurs, and the shape of that geyser is such that sonic reflections from the generally parabolic surface of the geyser effects a concentration of the sonic energy probably within the geyser itself to give optimum nebulization. Of course, maintaining the proper power density range over a larger area increases aerosol production.
The optimum power density range for nebulization of the various liquids, of course, can be quite different.
For a given oscillator power, the proper acoustical power density can also be obtained by slightly detuning the unit from a frequency which would give a violent geyser with a given transducer and thus decreasing the electro-acoustical transducers efficiency. This method of power density control can, however, reflect in undue heating of the equipment.
While the apparatus of the present invention is primarily intended for nebulizing fluids for inhalation therapy, it has also been found to be effective for emulsifying immiscible liquids in small quantities, for example, in those cases where an extremely expensive materiat must be suspended in an inexpensive carrier. It has also been found to be useful in producing a fog of antiseptic materials for room sterilization because the small particle size of the aerosol has substantially enhanced penetrating power.
In its method aspects, the primary object of the present invention is to provide a new method of forming an aerosol of a liquid suitable for inhalation therapy, which method is characterized by the creation of a large volume of aerosol particles by means of ultrasonic energy focused within the geyser ultrasonically formed on the surface of the treatment liquid.
Other objects and advantages of the invention will become apparent from the following detailed description of a preferred form thereof, reference being had to the accompanying drawings, in which:
FIG. 1 is a diagrammatic view, with parts in section and parts broken away of an apparatus constructed in accordance with the present invention and arranged to carry out the method thereof;
FIG. 2 is a somewhat enlarged, central vertical sectional view, of a portion of the apparatus in which medicament nebulizing is accomplished;
FIG. 3 is a sectional view on line 33 of FIG. 2;
FIG. 4 is a detail cross-sectional view of a member, the center portion of which constitutes an acoustically transparent diaphragm and that forms a portion of the lower wall of the medicament chamber;
FIG. 5 is a central vertical sectional view of the preferred form of electro-acoustic transducer, with the electrode layers thereof being exaggerated in thickness;
FIG. 6 is a fragmentary cross-sectional view of a nebulizer having a modified form of electro-acoustic transducer; and
FIG. 7 is a fragmentary cross-sectional view of a nebulizer having still another modified form of electroacoustic transducer.
Referring to FIGURES 1 and 2 of the drawings, an apparatus embodying the present invention comprises a lower housing 10 in which an electro-acoustical transducer is mounted, the transducer being in the form of a spherically curved piezoelectric crystal or crystalline mass such as a lead zirconate titanate ceramic 12, excited in the thickness mode from a suitable oscillator '14, and transmitting into a body of coupling liquid 15 which is contained in a chamber 16. The chamber 16 is preferably an open top vessel having a flanged extension 18 and a pouring lip 19 so that it can be conveniently emptied when necessary.
The transducer 12 has an electrically conductive coating on its front face that extends over the edges of the spherical body onto the rear surface thereof, which coating forms a ground electrode 20 of the energizing circuit. Spaced inwardly from the electrode 20 formed by the above-described coating, and separated therefrom by an annular band of the insulating ceramic material of the transducer is an electrode 21 which is connected to one side of the oscillator 14 through a spring contact 21w. Thus both electrical connections to the transducer are made on the rear face thereof and away from the face that is in contact with the coupling liquid. The resonant frequency of operation depends, of course, on the material and physical dimensions of the transducer and on its mounting. The transducer 12 is preferably a spherically ground body of lead zirconate titanate ceramic, polarized in the direction of its thickness, although a fiat transducer similarly polarized may be used as hereinafter described. A resonant frequency of 1.25 megacycles per second has been found to be satisfactory although higher or lower frequencies in the ultrasonic rangemay be used. A transducer resonating at 1.25 megacycles per second is more rugged and less expensive than one operating at higher frequencies.
The transducer is mounted in position in the bottom of the chamber 16 against an O-ring 22. A follower ring 23 contacts the underface of the crystal 12 adjacent its edges and is in electrical contact with the annular ground electrode 20, and the follower ring is urged against the transducer by a plurality, preferably three, of coil springs 24 disposed between the follower ring 23 and the bottom of the housing 16. The ground electrode 20' is thus connected to the oscillator 14 by the follower ring, the springs 24 and a suitable conductor. By mounting the transducer in this manner, the effect of any temperature changes that might cause expansion of the parts and stress on the relatively fragile transducer 12 are minimized and yet the escape of coupling liquid into the bottom of the housing is effectively prevented. It will be appreciated that a change in stress around the edge of the transducer 12 will change its operating characteristics and may even crack it.
The nebulizing chamber comprises a vessel 26 carried on a lower ring 27 and removably supported by suitable legs 28 on the flange surface 18 of the lower chamber or housing 16. A transparent cover is preferably used to close and seal the open upper end of the vessel. The bottom surface of the vessel 26 includes a downwardly tapered wall 29 having a central opening 30, and 21 diaphragm 31 is clamped against the wall 30 by an annular clamp ring 32. The diaphragm 3-1 is made of a thin acoustically transparent plastic membrane such as Mylar and has a center portion that is molded into a central downwardly extending spherically curved window 33. The Mylar diaphragm need be only two or three thousandths of an inch thick; enough to be self-sustaining and sufficiently rugged to withstand normal handling. A pierced or broken diaphragm can be easily replaced by removing the clamp ring 32.
By utilizing the downwardly extending spherically curved window 33, it has been found that there is no need to de-gas the coupling liquid 15 contained within the chamber 16. Any bubbles that appear in this liquid due to the agitation caused by the energy radiated from the transducer 12 will float upwardly around the convex surface of the window 33 and will not collect on this lower surface to cause interference with the transmission through the diaphragm. The spherically curved window has the additional advantage that it permits small amounts of liquid on its concave upper surface to be subjected to the sound transmission and concentrated in the center area where the acoustical energy is of the desired density.
When a continuous feeding of liquid is indicated, the level of liquid within the nebulizing chamber may be maintained at a preselected level by any suitable automatic means. A simple float operated valve including a toroidally shaped float 40 pivotally connected to a needle valve 41 by a lever fulcrumed at 42 may be used to control the opening of a supply line 43. In the form shown in the drawings this supply line comprises a tubular inlet pipe connected at its upper end to a supply conduit 44 and fixed adjacent the wall of the nebulizing chamberby a connector 45. The supply conduit 44 in turn connects to a jar of the liquid which it is desired to nebulize flow to the nebulizer being caused by gravity. When the level of liquid in the nebulizing chamber falls, the float causes the needle valve 41 to open, and when the level has risen to the preselected point, the float closes the inlet supply valve.
The energy radiated from the transducer 12 to the liquid ini the nebulizing chamber 16 causes the liquid to be thrown upward in the nebulizing chamber. By establlshing a relatively Wide zone of application of the acoustic energy to the surface of the liquid, the geyser is lower and the-output of suitable aerosol is increased. A sharply focused beam of sonic energy produces a violent, high geyser butvirtually no aerosol. In general, the size of the resulting droplets will vary inversely with the frequency of operation, a higher frequency causing the appearance of smaller droplets. For inhalation therapy droplets between about 1 micron and about 6 microns are believed to be desirable. However, at the lower side of this range, the droplets are so fine that many of them are rebreathedjI-and are less effective for treatment. At the upper end of the stated range the-droplets exhibit a pronounced tendency to settle out and not all of the liquid will enter the respiratory tract of the patient and very little of the liquid will enter the lungs for deep therapy. Between about 2 and 4 microns in particle diameter the droplet size appears to be optimum, very little of the liquid being re-breathed and very little of it settling out even though the aerosol may be transmitted through several feet of tubing from the nebulizer to the patient.
One form of the present invention provides a motor driven blower 50 which causes a current of carrier gas to pass.th'rough the nebulizing chamber and forces the nebulized particles through a discharge fitting 51 and into a conveying tube 52. A settling trap in the form of an upwardly extending arm 53 having a cover 54 is provided to separate any large droplets that might have been carried away with the desired aerosol or finely nebulized material. These droplets collect on the plate 54 and fall back through the discharge fitting 51 into the nebulizing chamberuWhile the forceable removal of nebulized particles from the nebulizing chamber by the carrier gas stream is desirable, a demand type of nebulizer is sometimes used in which aerosol accumulates in the nebulizing chamber and is extracted therefrom by the breathing of the patient. The nebulizer of the present invention may be so operated if the blower 50 is turned off or not used.
It will be apparent that instead of passing air from blower 50 through the nebulizing chamber, other gases may be used to remove the aerosol from the nebulizing chamber to the patient, and that this gas may he oxygen if desired or, in many instances, may be an anaesthetic gas so that the aerosol is used to improve the humidity of the anaesthetic material. The present invention may also be useful in the introduction of contrast media into the lungs of a patient to facilitate X-ray examination and diagnosis.
Nebulizers are frequently used unattended, and there is the possibility that the supply of liquid to the nebulizing chamber may become exhausted. If this happens, the continued operation of the transducer 12 might burn the thin window 33 and puncture it. It is therefore desirable to control the operation of the transducer thermostatically in accordance with the attained temperature of the lower vessel 16 which reflects the temperature of the coupling liquid 15. A thermostat T is shown diagrammatically in FIG. 2 in position to accomplish this control. If the coupling liquid becomes too hot, the transducer should be turned off not only to save the window 33 but to save the transducer itself since some transducer materials are not capable of withstanding temperatures in excess of C. without depolarization, and the coupling liquid is relied on to cool the transducer.
In operating the nebulizer described above, the coupling liquid container 16 is filled with water which, as above noted, need not be de-gassed. The previously sterilized nebulizing chamber or vessel 26 is placed on the flanged surface of the lower housing and connections to the medicament jar are made through conduit 44 and connections to the blower 50 and to the discharge tube 52 are likewise established. These connections may be simply frictional connections between a flexible tube and the appropriate fittings on the vessel 26. The nebulizing vessel 16 will fill promptly from its supply jar until the float controlled valve 41 is closed by its float. The oscillator 14 may then be turned on and the nebulizing chamber will immediately fill with a dense mass of very finely divided or air-borne nebulized liquid. The blower 50 will operate to convey the aerosol from the nebuilizing chamber through the discharge tube 52 to the patient.
The oscillator 14 is initially adjusted to the resonant frequency of the transducer 12 and is then de-tuned to drive the transducer at a frequency above its resonant frequency. We have found that a transducer having a designed resonant frequency of 1.25 megacycles per second operates to produce a maximum volume of aerosol when driven at about 1.35 megacycles per second. The adjustment of the oscillator can be made visually because the aerosol output in the vessel 26 is noticeably affected by a change in frequency of the oscillator and thus of the transducer 12. As previously noted, the appearance of a dense fog of nebulized material accompanying a low, broad geyser is indicative of satisfactory adjustment. The operation of the blower 50 may be adjusted to increase or decrease the throughput of air or carrier gas and thus increase or decrease the quantity and density of aerosol supplied to the patient and, if desired, the positive pressure created by the blower may be dispensed with and the vessel 26 used as a supply of aerosol to be drawn therefrom on demand by the patient.
Controlling the quantity and density of the aerosol supplied to the patient from the apparatus of the present invention is desirable, because the peak aerosol density that is obtainable is much greater than can be initially tolerated by the patient in some instances. In certain inhalation treatments, the attending physician will cause the patient to breathe a relatively dilute aerosol solution and then increase its density gradually until the desired density of the unit is reached. If the full density were to be used at the beginning of the treatment, certain results of the treatment might be lost because of the inability of the patient to tolerate the high density aerosol without coughing or otherwise refusing to inhale the medicament.
If the apparatus of the present invention is used as a nebulizer to produce a fog of antiseptic material for room sterilization, or for similar uses where it is not important that a separate, sterilizable medicament chamber be provided, the diaphragm 31 may be dispensed with and the liquid that has been previously denoted as a coupling liquid may become the nebulized material. In this instance, a float controlled valve will be used to maintain the level of liquid substantially constant but there will be no separation of the medicament and coupling liquids as such, these two liquids being, in this case, the same.
Under these circumstances the upper and lower containers 16 and 26 could be made as a single vessel.
FIG. 6 shows a portion of a nebulizer having a modified form of the transducer system. In this form the transducer mass is a flat-ground plate 120 of piezoelectric material which will radiate plane-parallel waves into the coupling liquid. An acoustic lens 121 is provided which may comprise a double concave body of Lucite or polystyrene resin having a central orifice 122 to allow the circulation of coupling liquid. The electrical energy is brought into the plate 120 by a peripheral electrode 123 which extends across the front of the transducer and around to the margin of the rear face, and by the central electrode 124 which is confined to the rear face as in the form shown in FIG. 2. Contact to these electrodes from the oscillator are made as previously described.
In the operation of this modified form of the invention, the ultrasonic energy orginating in the transducer is focused by the lens 121, and the focal point is well above the medicament chamber as before. The operation is the same as previously described except for the arrangement by which a focused beam of ultrasonic energy is caused to pass through the coupling liquid into the medicament chamber.
FIG. 7 shows an alternate form in which a flat transducer is used, the transducer itself being designated by the reference number 140'. Power is supplied thereto through connectors 141 and 142. The transducer 140 vibrates to project its compressional wave energy upwardly through the liquid to the surface thereof where a broad, dome-like geyser is formed. The sound waves appear to come to a focus within the geyser by reflection from the air-liquid interface to form a high concentration of suitably nebulized liquid as indicated at 143 in FIG. 7.
In the operaton of the modified form of the invention shown in FIG. 7, the proper level of ultrasonic power density at the surface of the liquid is not achieved by a focusing electro-acoustical transducer through a coupling liquid or by a focusing system located below the normal liquid level, but rather is obtained by exciting a nonfocusing transducer by a much higher power density than is applied to the transducer in a focusing system. Since the focusing is achieved within the geyser itself when proper power density is applied at the liquid surface, the liquid level is not critical and a liquid-level control means is not required.
In the case of a nebulizer employing the construction of FIGURE 2, it has been found that if a unit having a transducer with a resonant frequency of 1.25 mc. and which is a 2" diameter segment of a 3% radius sphere, and if the normal liquid level is maintained approximately 2%" from the center of the transducer, nebulization can be effected if 1.35 mc. electrical power is applied in a range from approximately 20 to approximately 100 watts. Approximately the same power density at the normal surface level could be obtained by applying the same power to a flat transducer with a diameter of approximately 1".
When flat transducers are utilized without lenses or other auxiliary focusing devices, as shown in FIG. 7, care must be taken to maintain the power density sufficiently low to prevent fatigue of the transducer or erosion of the face of the transducer due to cavitation.
FIGS. 2, 6 and 7 show diagrammatically the broadbased geyser in which concentration of the sonic energy occurs, probably by reflection from the Walls of the geyser itself. Such a geyser has been found to be most effective, but in practice it is diflicult to make a precise examination of the geyser because of the presence of the dense aerosol or fog within the chamber 26. Attempting to blow the fog away to examine the geyser probably results in distorting the configuration thereof.
It will be appreciated that other transducer configurations may be used, and that various modifications and changes may be made in the remainder of the elements without departing from the scope of the appended claims.
What we claim is:
1. In an apparatus for creating an aerosol for medical purposes, the combination of, means forming a chamber for containing an acoustic coupling liquid, a body of coupling liquid in said chamber, an electro-acoustic-transducer system, said transducer system having a transducer forming at least a portion of a lower wall of said chamber and so constructed and arranged that when energized beams of ultrasonic energy pass through said coupling liquid, a separable medicament chamber disposed over said coupling liquid chamber and having an acoustically transparent lower wall immersed in said coupling liquid, means to control the level of liquid medicament in. said medicament chamber, the focal point of said transducer system being within said medicament chamber but above the level of liquid medicament therein, said beams of sonic energy intersecting the surface of said medicament liquid in a broad zone, means to energize said transducer system at a power density per unit of transducer area that will cause violent agitation and cavitation of the surface of said liquid medicament and said beams of sonic energy come to a focus within a geyser thrown upwardly therefrom, whereby to cause the dispersal of said liquid medicament into an aerosol of medicament droplets, and means to remove said aerosol from said medicament chamber.
2. The combination of elements defined in claim 1 in which said means to control the level of said liquid medicament includes a float operated valve.
3. The combination of elements defined in claim'Z in which said float operated valve includes a toroidal "float and said ultrasonic energy passes into the torus of, said float.
4. The combination of elements defined in claim 1 in which said means to remove said aerosol from said'rnedicament chamber includes a positive pressure means to induce air flow through said chamber. i
5. The combination of elements defined in claim ,1 in which said separable medicament chamber has an acoustically transparent thin window in its lower wall, 'said window having a convex surface exposed to the coupling liquid, whereby bubbles formed in said coupling liquid will float upwardly away from said convex surface.
6. The combination of elements defined in claim 1 in which said electro-acoustic transducer is driven at a frequency above its resonant frequency to produce the maximum volume of aerosol within said medicament chamher.
7. The combination of elements defined in claim 1 in which said electro-acoustic transducer is driven at a frequency greater than one megacycle and at a frequency about kilocycles per second above its resonant frequency to produce the maximum volume of aerosol within said medicament chamber.
8. The combination of elements defined in claim 1 in which said electro-acoustic transducer has a resonant frequency of 1.25 megacycles per second and is driver; at a frequency of 1.35 megacycles per second to produce the maximum volume of aerosol within said medicament chamber.
9. In an apparatus for creating an aerosol for medical purposes, the combination of means forming a first chamher, a body of liquid to be nebulized in said chamber, an electro-acoustic transducer system having a transducer forming at least a portion of the bottom wall of said chamber and so constructed and arranged that when energized beams of ultrasonic energy pass through said body of liquid, a nebulizing chamber disposed over said first chamber, said beams of ultrasonic energy intersectg ing the surface of liquid to b nebuilized in said nebulizing chamber in a broad zone, means to energize said transducer system at a power density per unit of transducer area that will cause violent agitation and cavitation of the surface of the liquid in said nebulizing chairiber, whereby said beams of ultrasonic energy come:to a focus within a geyser thrown upwardly therefrom to cause dispersal of said liquid into an aerosol, and means to remove said aerosol from said nebulizing chamber.
10. In an apparatus for creating an aerosol for medical purposes, the combination of, \means forming a chamber for containing an acoustic coupling liquid, a body of coupling liquid in said chamber, an electro-acoustic transducer system, said transducer system having a transducer forming at least a portion of a lower wall of said chamber and so constructed and arranged that when energized beams of ultrasonic energy pass through said coupling liquid, a separable medicament chamber disposed over said coupling liquid chamber and having an acoustically transparent lower wall immersed in said coupling liquid, said beams of sonic energy intersecting the surface of said medicament liquid in a broad zone, means to energize said transducer system at a power density per unit of transducer area that will cause violent agitation and cavitation of the surface of said liquid medicament and said beams of sonic energy come to a focus within a geyser thrown upwardly therefrom, whereby to cause the dispersal of said liquid medicament into an aerosol of medicament droplets, and means to remove said aerosol from said medicament chamber,
11. The combination of elements defined in claim 10 in which said transducer has its active face spherically curved.
12. The combination of elements defined in claim 11 in which the center of curvature of said transducer lies substantially above the normal level of liquid to be nebulized.
13. The combination of elements defined in claim 10 in which said transducer has a fiat active face.
14. The combination of elements defined in claim 9 in which said transducer has a fiat active face.
References Cited UNITED STATES PATENTS 2,855,526 10/1958 Jones 259-1 XR 3,291,122 12/1'966 Engstrom et al. 128173 XR FOREIGN PATENTS 1,003,147 2/ 1957 Germany.
1,056,065 4/1959 Germany.
RICHARD A. GAUDET, Primary Examiner, W. E. IQKMM, Examiner,
UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,387,607 June 11, 1968 William D. Gauthier et a1.
It is certified that error appears in the above identified patent and that said Letters Patent are hereby corrected as shown below:
Column 1, line 41, after "condense," insert and thus have no therapeutic value. If the particles are too small, as for example one-half micron or less in diameter, a majority of the droplets will be exhaled or "re-breathed",
Signed and sealed this 21st day of October 1969.
ISEAL) meat:
WILLIAM E. SCHUYLER, JR.
Commissioner of Patents Edward M. Fletcher, Jr.
kttesting Officer
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US20180036498A1 (en) * 2015-04-09 2018-02-08 Aft Pharmaceuticals Limited Nasal Medication Delivery Device
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