WO1997017933A1 - Procede de pulverisation sur une surface, en utilisant des ultrasons - Google Patents

Procede de pulverisation sur une surface, en utilisant des ultrasons Download PDF

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Publication number
WO1997017933A1
WO1997017933A1 PCT/US1995/014926 US9514926W WO9717933A1 WO 1997017933 A1 WO1997017933 A1 WO 1997017933A1 US 9514926 W US9514926 W US 9514926W WO 9717933 A1 WO9717933 A1 WO 9717933A1
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WO
WIPO (PCT)
Prior art keywords
free end
liquid
end surface
transducer
spray
Prior art date
Application number
PCT/US1995/014926
Other languages
English (en)
Inventor
Eliaz P. Babaev
Original Assignee
Aeropag Usa, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Aeropag Usa, Inc. filed Critical Aeropag Usa, Inc.
Priority to PCT/US1995/014926 priority Critical patent/WO1997017933A1/fr
Priority to AU42380/96A priority patent/AU4238096A/en
Publication of WO1997017933A1 publication Critical patent/WO1997017933A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/005—Sprayers or atomisers specially adapted for therapeutic purposes using ultrasonics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61H—PHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H23/00—Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms
    • A61H23/02—Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms with electric or magnetic drive
    • A61H23/0245—Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms with electric or magnetic drive with ultrasonic transducers, e.g. piezoelectric
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
    • A61M11/001—Particle size control
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
    • B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
    • B05B17/06—Apparatus 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
    • B05B17/0607—Apparatus 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
    • B05B17/0623—Apparatus 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 coupled with a vibrating horn
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M35/00—Devices for applying media, e.g. remedies, on the human body

Definitions

  • the present invention relates to methods of using ultrasonic radiation in spraying applications.
  • the present invention relates to a method of spraying a surface using ultrasonic radiation for delivering drugs, killing bacteria, and cleansing a surface.
  • Ultrasonic radiation has been widely used in medical applications including both diagnostics and therapy as well as many other non-medical applications.
  • One diagnostic use of ultrasound radiation includes using ultrasonic radiation to detect underlying structures in an object or a human tissue.
  • an ultrasonic transducer is placed in contact with the tissue (or object) via a coupling medium and high frequency ultrasonic waves
  • the waves are directed into the tissue (or object).
  • the waves are reflected back to a receiver adjacent the transducer.
  • an image of the underlying structure can be produced.
  • This technique is particularly useful for identifying boundaries between components of tissue and can be used to detect irregular masses, e.g. , tumors. This technique can also be used to detect the underlying structure of objects other than human or animal tissue.
  • Aerosol mist production makes use of a nebulizer to produce an aerosol mist for creating a humid environment.
  • Ultrasonic nebulizers operate by passing a beam of ultrasound radiation of sufficient intensity through a liquid, the beam being directed at an air-liquid interface of the liquid from a point underneath or within the liquid.
  • Liquid particles are ejected from the surface of the liquid into the surrounding air following the disintegration of capillary waves produced by the ultrasonic radiation.
  • This technique can produce a very fine dense fog or mist and typically is used within a tent or canopy for maintaining a humid atmosphere in a ventilating system. Aerosol mists produced by ultrasonic radiation are preferred because a smaller particle size of the aerosol can be obtained with the ultrasonic radiation.
  • Anthony U.S. Patent 4,679,551 discloses an ultrasonic sprayer for producing a fine mist for moistening a mouth cavity and lips of a comatose or terminal patient.
  • the ultrasonic sprayer is mounted in the vicinity of the oral cavity of the patient and is positioned so that a very fine particle mist settles over the oral cavity of the patient.
  • areosol mists produced by ultrasound radiation are readily employed in non-medical applications as well.
  • Contact physiotherapy applies ultrasonic radiation directly to a tissue in an attempt to produce a physical change in the tissue.
  • an ultrasonic transducer contacts the tissue via a coupling medium.
  • Ultrasonic waves produced by the transducer travel through the coupling medium and into the tissue.
  • the coupling medium is typically a bath of liquid, a jelly applied to the surface to be treated, or a water filled balloon.
  • Conventional techniques provide ultrasonic waves having an intensity of about 0.25 W/cm 2 to 3 WVcm 2 at a frequency of about 1 to 3 Megahertz.
  • the treatment is applied to a skin surface for 5 to 20 minutes, two or three times a week.
  • the coupling medium can provide a cooling effect which dissipates some of the heat energy produced by the ultrasonic transducer. More importantly, a coupling medium or direct contact between the tissue and the ultrasonic transducer is necessary to transmit the ultrasonic waves from the transducer to the skin surface because ambient air is a relatively poor medium for the propagation of high frequency ultrasonic waves.
  • tissue conditions may be accessible to contact ultrasound devices but would be impractical for contact ultrasound treatment.
  • open wounds resulting from trauma, burns, surgical interventions are not suitable for direct contact ultrasound treatment because of the structural nature of the open wound and the painful condition associated with those wounds.
  • conventional contact ultrasound may have a destructive effect on these types of open wounds due to the close proximity of an oscillating tip of an ultrasonic transducer relative to the already damaged tissue surface.
  • the present invention is a method of spraying a surface to deliver drugs, kill bacteria, or cleanse a surface by noncontact application of ultrasonic waves and ultrasonically activated liquids.
  • the method applies ultrasonic radiation to a surface, such as tissue, object, or food without requiring direct or indirect (via a conventional coupling medium) contact between the ultrasonic wave transducer and the surface to be sprayed.
  • the method includes producing a particle spray of liquid particles produced by contact of the liquid with a free end surface of an oscillating ultrasonic transducer.
  • the particle spray is directed onto the surface (e.g., tissue or object) while maintaining the free end surface at a distance relative to the surface to be sprayed.
  • the ultrasonic waves cause the spray to project outwardly from the free end surface and the particles of the spray provide a medium for propagation of the ultrasonic waves emanating from the free end surface.
  • the particle spray created by low frequency ultrasound radiation
  • the particle spray can devlier a drug to the tissue (via the surface) in addition to killing bacteria and removing dirt and debris on the tissue surface.
  • This method of drug delivery is particularly advantageous on tissues for which local topical application of a drug is desirable yet contact with the tissue is to be avoided.
  • the low frequency ultrasound radiation used in the method accentuates the action of the drug and causes penetration of the drug below the surface of the tissue.
  • the bacteria killing method is effective when applied to a surface whether the liquid sprayed is distilled water, an antiseptic, or antibiotic.
  • the step of producing the spray can further include first delivering the liquid to a side surface of the transducer adjacent to the free end surface such that the liquid is pulled to the free end surface by a vacuum created by the ultrasonic waves on the free end surface of the transducer tip.
  • the step of producing the spray can further include operating the transducer to produce longitudinal ultrasonic waves having a frequency of about 16 to 200 kilohertz with a preferred range of frequency of about 20 to 40 kilohertz.
  • the step of directing the spray can further include maintaining a distance of separation between the free end surface of the transducer and the surface to be sprayed of preferably about 0.5 to 10 centimeters.
  • the liquid can further include an antibiotic for application to the tissue.
  • the method can include directing the spray onto the surface for about 30 to 60 seconds on a daily or semidaily basis, or at such durations, intervals, frequency, and distances as determined in the judgment of the user.
  • the method of the present invention permits application of ultrasonic waves to surfaces without establishing contact, directly or indirectly, between the ultrasonic transducer and the surface (e.g., tissue).
  • surfaces of the human body especially suited for treatment with the method of the present invention include infected and inflammatory processes in open wounds including firearm wounds, fire and chemical burns.
  • the method of the present invention is particularly suited to directing a spray into orifices or other body crevices that are difficult to access.
  • inflammation of both the tympanic membrane of the ear and of the middle ear resulting from otitis media are especially suitable to spray using this method.
  • the orienting step could further include orienting the particle spray into the external auditory canal of the ear to project the spray directly onto the tympanic membrane of the ear while maintaining a distance of separation of preferably about 0.5 to 10 centimeters between the tympanic membrane and the transducer tip.
  • This method of spraying a surface has several advantages.
  • this method topically applies medicines such as antibiotics to the tissue surface (e.g. , tympanic membrane or burn wound) without the need to contact an infected and inflamed tissue with an instrument for directly applying the antibiotic to the membrane.
  • the following bacteria, amongst others, found on the surface of human tissues have been shown to be effectively treated with the method of the present invention including: pseudomonas aeroginesa, the family of staphylococcus bacteria, and yeast bacteria Candidas albicans.
  • the method of the present invention results in a 50 to 70 percent reduction in volume used of antibiotic medicine used as compared with traditional methods for killing bacteria on a wound surface. Similarly, this allows for precise dosage of the sprayed liquid to permit a user, such as a physician to administer the desired volume of liquid at a desired rate, frequency, and duration.
  • the ultrasonic radiation imparted onto the liquid media finely atomizes the different compositions to produce a uniform mixture of the different compositions that does not occur in traditional mixing methods of medicines.
  • the method of the present invention results in healing times for inflammatory and purulent infected wounds that is 11 ⁇ 2 to 2 times faster than traditional methods.
  • This effect results from a mechanical cleansing effect of the atomized spray particles which have vibratory energy due to the ultrasonic waves.
  • the spray mechanically scrubs the surface of tissue to remove dirt, dead tissue, and purulent buildup on the tissue surface.
  • the accentuated healing effect also results from accentuated drug delivery since the liquid medication penetrates into the tissue surface up to 1 millimeter in depth.
  • a combination of the low frequency ultrasonic waves and the insonified medicines i.e., highly activated by ultrasonic energy destroy the surface bacteria to result in a higher disinfecting property of insonified liquids as compared to ordinarily applied liquids.
  • the spray of the present method also stimulates healthy cell growth to aid in granulization and epithelization of the healing tissue.
  • the method of the present invention offers an approach that may re-establish use of some traditional antibiotics and establish a method fighting bacteria without antibiotics when necessary.
  • the effect of the method of the present invention in highly activating antibiotics may allow some traditional antibiotics to overcome bacteria which have become resistant to that antibiotic.
  • the low frequency ultrasonic waves applied in the method of the present invention physically destroy bacteria. Bacteria are unlikely to develop a resistance to this treatment.
  • the combination of the highly activated antibiotics and of the low frequency ultrasonic waves in the method of the present invention produce a strong bactericidal effect not found in mere topically application or orally ingested antibiotics. This combined effect has been shown to dramatically increase the healing of purulent infected wounds.
  • the present method also provides a system of noncontact drug delivery without using a compression sprayer system. This simplifies the design of a noncontact drug delivery sprayer and reduces the weight of the sprayer. More importantly, not using compression to propel the atomized particles preserves the ultrasound energy carried by the spray particles. This ultrasound energy has been proven to destroy bacteria by action of the ultrasonic waves and by highly activating the liquid medicines (e.g., antibiotics) applied to the tissue.
  • liquid medicines e.g., antibiotics
  • FIG. 1 is a perspective view of an ultrasonic sprayer system for use in a method of the present invention.
  • FIG. 2 is a view in section of the ultrasonic sprayer as used in a method of the present invention.
  • FIG. 3 is an enlarged view of FIG. 2 illustrating a spray created by the sprayer of FIG. 2 in the method of the present invention.
  • FIG. 4 is a perspective view of the ultrasonic sprayer as used in a method of the present invention for spraying an arm.
  • FIG. 5 is a view of the sprayer of FIG. 3 rotated relative to a horizontal plane.
  • FIG. 6 is a enlarged view in section of a modification of a tip of the sprayer as used in the method of the present invention.
  • FIG. 7 is a enlarged view in section of a modification of a tip of the sprayer as used in the method of the present invention.
  • FIG. 8 is a plan view of a modified tip of the sprayer of the method of the present invention.
  • FIG. 9 is a plan view of a modified tip of the spray as used in the method of the present invention.
  • FIG. 10 is a plan view of a modified tip of the sprayer of the present invention.
  • FIG. 11 is a plan view of a modified tip of the sprayer of the present invention.
  • FIG. 12 is a plan view of a modified tip of the sprayer of the method of the present invention.
  • FIG. 13 is a plan view of a modified tip of the sprayer of the method of the present invention.
  • FIG. 14 is a plan view of a modified tip of the sprayer of the method of the present invention.
  • FIG. 15 is a plan view of a modified tip of the sprayer of the method of the present invention.
  • FIG. 16 is a plan view of a modified tip of the sprayer of the method of the present invention.
  • FIG. 17 is a plan view of a modified tip of the sprayer of the method of the present invention.
  • FIG. 18 is a plan view of a modified tip of the sprayer of the method of the present invention.
  • FIG. 19 is an end sectional view of a sprayer taken along line 18- 18 in FIG. 2.
  • FIG. 20 is a sectional view of a modification of the sprayer shown in FIG. 2.
  • FIG. 21 is a view in section of a method of the present invention for treatment of an ear.
  • FIG. 22 is a photograph of a bacteria cell prior to treatment with the method of the present invention.
  • FIG. 23 is a photograph of a bacteria cell after treatment with the method of the present invention.
  • FIG. 24 is a photograph of a bacteria cell after extended treatment with the method of the present invention.
  • FIG. 25 is a photograph of a colony of bacteria cells after treatment with the method of the present invention. While the above-identified figures set forth the preferred embodiments, other embodiments of the present invention are also contemplated as noted in the discussion. In all cases, this disclosure presents illustrated embodiments of the present invention by way of representation and not limitation. Numerous other modifications and embodiments can be devised by those skilled in the art which fall within the scope and spirit of the principles of this invention. The figures have not been drawn to scale as it has been necessary to enlarge certain portions for clarity. In addition, the use of such relational terms such as left/right, upper/lower, top/bottom or horizontal/vertical etc. are used herein for reference purposes only and are not intended to be limiting features of the invention disclosed.
  • FIG. 1 A spraying system used in a method of the present invention is illustrated in FIG. 1 generally at 10.
  • the spraying system 10 is used for spraying liquids onto a surface and delivering ultrasonic radiation to a surface.
  • the system 10 includes an ultrasonic generator 12, a power cord 14, and a hand held sprayer 16.
  • the ultrasonic generator 12 includes a power switch 18, controls 20, and a display 22.
  • the power cord 14 includes a first end 24 and a second end 26.
  • the sprayer 16 has a first end 28, a second end 30, a housing 31 , and a liquid delivery mechanism 32.
  • the liquid delivery system 32 includes an arm 34, a mounting 36 (including a spring), and reservoir 38.
  • the reservoir 38 includes a pin 39.
  • the arm 34 of the system 32 includes a first end 40, a second end 42, and bent portion 44 between the ends.
  • the sprayer 16 is a modification of a device for ultrasonic atomization of a liquid medium as disclosed in U.S. Patent 5,076,266. The subject matter of U.S. Patent 5,076,266 is herein incorporated by reference in the present application.
  • the first end 24 of the power cord 14 is electrically connected to the ultrasonic generator 12 and the second end 26 of the power cord is electrically connected to the first end 28 of the sprayer 16.
  • the bent portion 44 of the arm 34 of the liquid delivery system 32 is rotatably mounted to the housing 31 of the sprayer 16 via mounting 36.
  • the second end 42 of the arm 34 is connected to the pin 39 on top of the reservoir 38.
  • the reservoir 38 is fixed to the second end 30 of the sprayer 16.
  • the ultrasonic generator 12 includes electrical circuitry known in the art for producing an electrical signal to cause longitudinal ultrasonic sound waves in the frequency of 16 to 1000 kilohertz on an ultrasonic transducer.
  • the controls 20 permit selection of the frequency as desired.
  • the display 22 shows the current frequency of the signal produced by the generator 12.
  • the power cord 14 provides an electrical connection between the generator 12 and the sprayer 16 for carrying the signal produced by the generator 12.
  • the sprayer 16 includes means for receiving the signal from the generator 12 and producing ultrasonic waves to create an atomized particle spray of liquid.
  • the second end 40 of the arm 34 of delivery system 32 is pressed downward causing rotation of the arm 34 about the mounting 36 and a lifting of the arm end 42 and the pin 39 atop the reservoir 38.
  • This causes liquid to flow out of the reservoir 38 and come into contact with the ultrasonic transducer inside the sprayer 16 to produce a spray from the second end 30 of the sprayer 16.
  • the spray stops upon releasing the arm 34 due to the bias of the spring in mounting 36 which returns the liquid delivery system to a closed state.
  • FIG. 2 further illustrates the sprayer 16.
  • the liquid delivery system 32 of the sprayer 16 includes the arm 34 and the reservoir 38.
  • the reservoir 38 has a lower portion 46, an upper portion 48, and a top plate 50 including an aperture 51.
  • a liquid 52 is held within the reservoir.
  • the pin 39 has a lower end 54, an upper end 56, and a collar 57.
  • the end 42 of the arm 34 also includes an aperture 58.
  • the second end 30 of the sprayer 16 further includes an upper portion 60 and a channel 62 with an opening 63.
  • a shroud 61 extends from the upper portion 60.
  • the second end 30 of sprayer 16 also includes an aperture 64, an inner wall 65, a bellmouth 66, and a cavity 68 within the housing 31.
  • the sprayer 16 also has an ultrasonic transducer 70 including a concentrator 71 and a vibrator 73.
  • the concentrator 71 includes a tip 74 having a free end surface 75 and a side surface 76.
  • the top plate 50 is secured within the upper portion 48 of the reservoir 38.
  • the upper end 56 of the pin 39 extends through and is slidably received within the aperture 51 of the top plate 50 and the aperture 58 of the end 42 of the arm 34.
  • the collar 57 of the pin 39 secures the pin 39 onto the end 42 of the arm 34.
  • the pin 39 extends through the reservoir 38 and the lower end 54 of the pin 39 removably fits within the opening 63 of the channel 62.
  • the channel 62 is in fluid communication with the aperture 64 at the second end 30 of housing 31. As shown, the lower end 54 of the pin 39 blocks the opening 63 of the channel 62.
  • the transducer 70 extends through the cavity 68 of the housing 31 with the tip 74 of the concentrator 71 extending coaxially through the aperture 64.
  • the free end surface 75 of the concentrator 71 is disposed at an open end of the aperture 64.
  • the side surface 76 of the tip 74 is disposed adjacent the channel 62.
  • the bellmouth 66 is secured within the cavity 68 of the housing 31 to the inner wall 65 of the housing 31 and encompasses the concentrator 71.
  • the ultrasonic transducer 70 selectively produces longitudinal sound waves in the ultrasonic frequency range.
  • the sound waves are produced by the ultrasonic vibrator 73 (initiated and controlled by a signal from the ultrasonic generator 12) and are focused as the waves travel through the concentrator 71 toward the tip 74 of the transducer 70.
  • the waves travel through the transducer 70 to the free end surface 75 of the transducer 70 where the waves meet the interface of the transducer 70 and the surrounding ambient environment.
  • the bellmouth 66 further focuses the waves emanating from the free end surface 75 of the transducer 70.
  • FIG. 2 illustrates the liquid delivery system 32 in a first closed position in which the end 54 of the pin 39 blocks the opening 63 of the channel 62 thereby preventing flow of the liquid 52 into the channel 62. Accordingly, although the ultrasonic transducer 70 may be producing ultrasonic waves at the free end surface 75, no spray of liquid is produced in this first closed position of the liquid delivery system 32.
  • FIG. 3 illustrates the liquid delivery system 32 of the sprayer 16 in a second open position in which the end 54 of the pin 39 permits the liquid 52 to flow into the channel 62 to produce a spray 80 of particles 82 upon contact of the liquid 52 with the transducer 70.
  • the biasing action of the spring mounting 36 is overcome and the second end 42 of the arm is rotated clockwise via the rotatable mounting 36.
  • the droplets 83 of liquid 52 contact the side surface 76 of the transducer tip 74 adjacent the free end surface 75.
  • the fluid 52 is not under pressure or compression within this sprayer system 10.
  • the fluid reservoir 38 is not pressurized such that the liquid passing through channel 62 to side surface 76 of transducer tip 74 does so by simple gravitational forces.
  • the ultrasonic transducer 70 of the sprayer 16 produces longitudinal ultrasonic waves that emanate from the free end surface 75 of the transducer tip 74. As seen in FIG. 3, the free end surface 75 is directly exposed to the surrounding environment, i.e., is not enclosed within the second end 30 of housing 31.
  • the ultrasonic waves can have a frequency in the range of 16 kilohertz to 200 kilohertz but are preferably in the range of 16 to 150 kilohertz. A most preferred range is from 16 to 40 kilohertz and the most preferred frequency is about 26 kilohertz.
  • the amplitude of the waves is preferably about fifty microns produced with an intensity of about 1.5 W/cm 2 .
  • the droplets 83 Upon contact with the side surface 76 of transducer tip 74, the droplets 83 become more finely dispersed to form smaller droplets 84.
  • the droplets 84 of liquid e.g. , antibiotic or other liquid
  • the ultrasonic waves emanating from the free end surface 75 of transducer tip 74 create a negative pressure (i.e., vacuum force) on the free end surface 75. This vacuum effect pulls the insonified droplets 84 of liquid 52 from the side surface 76 onto the free end surface 75.
  • the longitudinal waves emanating from the oscillating free end surface 75 cause the droplets 84 of the liquid 52 to become even more finely dispersed, i.e. , atomized, and to be forcefully jettisoned or directed outwardly into the ambient environment away from the free end surface 75 in the form of the spray 80 of particles 82.
  • the atomized particles 82 of the liquid 52 are further pushed through the air by the longitudinal ultrasonic waves emanating from the transducer tip 74 at free end surface 75.
  • the particle spray 80 projects outwardly from the transducer tip 74 in a direction substantially parallel to a longitudinal axis of the sprayer 16.
  • the atomized spray 80 in combination with the ambient air provides a medium for allowing propagation of (i.e., transmitting) ultrasonic waves emanating from the free end surface 75.
  • the arm portion 40 is released thereby causing the pin 39 to move downwardly into the first closed position to block opening 63 and close access to the channel 62.
  • the spray 80 projects horizontally from the transducer tip 74 of the sprayer 16 and carries the ultrasonic waves emanating from the free end surface 75.
  • the spray 80 projects outwardly from the transducer tip 74 onto a surface 85 of a tissue 86.
  • the sprayer 16 is held relative to the tissue 86 so that a distance of separation DI is maintained between the surface 85 of the tissue 86 and the free end surface 75 of the transducer tip 74.
  • the distance of separation between the tissue surface 85 and the free end surface 75 of the ultrasonic transducer is preferably about 0.5 to 10 centimeters but can extend up to 15 to 20 centimeters as deemed necessary by the user.
  • the distance of separation should be at least 1 millimeter so that contact is avoided.
  • the liquid spray 80 projects toward the tissue surface 85 and a combination of the liquid spray and the ambient air carry, i.e., facilitate propagation of, the ultrasonic waves from the free end surface 75 of the transducer tip 74 from the sprayer 16 onto and into the tissue surface 85.
  • the projected spray 80 of the liquid antibiotic 52 causes the liquid 52 to penetrate the tissue surface 85 at a depth D3 of about 1 millimeter and causes the ultrasonic waves to similarly penetrate the skin at a depth D3 of about 1 millimeter. (See FIG. 3).
  • the volume of the spray 80 can be increased or decreased by controlling the rate at which the liquid 52 is directed to the free end surface 75.
  • a respective depressing or uplifting of the arm second portion 40 causes a respective opening and closing of the channel 62 by the pin 39.
  • the pin 39 When the pin 39 is raised from its first closed position, fluid 52 flows through the channel 62 and onto the side surface 76 of transducer tip 74 and is ultimately atomized off free end surface 75.
  • Selective lowering of the pin 39 within the reservoir 38 reduces the amount of liquid 52 flowing into the channel 62 and reaching free end surface 75 thereby reducing the volume of spray 80.
  • a method of the present invention of spraying a surface can be illustrated with a method of spraying an open wound of a human arm as illustrated in FIGS. 3 and 4. As shown in FIG.
  • the sprayer 10 is brought into proximity with an arm 87A having an open wound 87B.
  • the open wound 87B can be a burn wound or other skin surface condition in which normal healing of the skin surface fails to occur and in which killing bacteria on the wound, delivering antibiotics to the wound, and cleansing the wound is critical.
  • the open wound is a purulent infected wound resulting from trauma in which the surface of the skin has been scraped off the arm thereby creating the open wound surface 87B.
  • the wound surface can have several bacteria and pathogenic flora acting on the exposed tissue preventing the normal healing processes and causing purulent inflammation of the wound 87B.
  • the most common bacteria include staphylococci (s aureus and epidermis) and pseudomonas aeruginosa as well as pathogenic microflora including grampositive diplococci, gram-negative bacilli.
  • the first step of the method includes providing a liquid for spraying the open wound 87B.
  • the liquid 52 typically includes a single medicine or a combination of medicines such as antibiotics, oxidants, antimicrobials, as well as sulfanilamides.
  • the liquid 52 is placed in the reservoir 38 of the sprayer 16.
  • the liquid 52 can also include distilled water alone or in combination with antibiotics or another medicinal agent.
  • the next step of the method for spraying the open wound includes directing the liquid, e.g., antibiotics, to the free end surface of the transducer tip wherein an atomized particle spray of the liquid is created upon contact of the liquid with the free end surface of the transducer. Particles of the spray carry the ultrasonic radiation imparted by the free end surface.
  • directing the liquid 52 to the free end surface 75 includes the following steps. Upon depressing arm portion 40, the pin 39 is moved from its first closed position (FIG. 2) to the second open position (FIG. 3) allowing droplets 83 of the liquid antibiotic 52 to travel down the channel 62 and onto the side surface 76 of the concentrator 71 at the transducer tip 74.
  • the particles 82 are insonified, i.e. , highly activated, upon contact with the side surface 76.
  • the method further includes the liquid droplets 84 being pulled to the free end surface 75 by a vacuum effect (i.e. , negative pressure) resulting from ultrasonic waves emanating from the free end surface 75.
  • a vacuum effect i.e. , negative pressure
  • the spray 80 of particles 82 is produced and projects outwardly from the free end surface 75 as seen in FIG. 3.
  • 87B further includes the step of orienting the particle spray directly onto the tissue 87B while maintaining a distance of separation between the tissue 87B and the free end surface 75 of the transducer 70.
  • the spray 80 projects horizontally from the second end 30 of the sprayer 16.
  • Orienting the spray 80 includes holding the sprayer 16 manually (or with an instrument) so that the spray 80 projecting outwardly from the transducer tip 74 of the sprayer 16 is aimed at the surface of wound 87B on arm 87 A.
  • the sprayer 16 is held relative to the wound 87B so that a distance of separation is maintained between the wound 87B and the free end surface 75 of the transducer tip 74 of the sprayer 16.
  • the method further includes holding the sprayer 16 so that the distance of separation between the wound 87B and the free end surface 75 of the ultrasonic transducer is preferably about 0.5 to 10 centimeters.
  • the distance can extend up to 15-20 centimeters if necessary although these larger distances (15-20) are not preferred. In any case, the user of the device can use their judgment and skill and select the appropriate distance. At a minimum, the distance of separation should be at least 1 millimeter to avoid contact.
  • the liquid spray 80 projects toward the wound surface 87B and a combination of the liquid spray and the ambient air carry, i.e. , facilitate propagation of, the ultrasonic waves from the free end surface 75 of the transducer tip 74 from the sprayer 16 onto and into the wound surface 87B.
  • the projected spray 80 of the liquid antibiotic 52 causes the liquid 52 to penetrate the wound surface 87B at a depth of about 1 millimeter and causes the ultrasonic waves to similarly penetrate the skin at a depth of about 1 millimeter.
  • FIG. 3 schematically illustrates this penetration.
  • the step of orienting the spray includes orienting the spray onto the wound 87B for about 30 to 60 seconds and up to five minutes.
  • the spray 80 can be oriented onto the wound 87B for less than 30 seconds (e.g. , 5 or 10 seconds) or more than 5 minutes, the range of 30 seconds to five minutes is preferred.
  • the user can select the duration of treatment and distance of separation as well as the volume administered.
  • the spray can be oriented onto the tissue either by maintaining the sprayer 16 in a position stationary relative to the wound 87B or by using a back and forth sweeping motion of the sprayer 16 to cover a larger entire wound surface 87B.
  • the step of orienting the spray can further include orienting the spray upwardly (toward the vertical) at an inclined angle directly onto a tissue.
  • the sprayer 16 can be manually held such that the longitudinal axis of the housing 31 is at an angle (e.g., 30°) relative to a horizontal plane A-A to cause the spray 80 to be forcefully directed onto the tissue surface 85 (e.g., wound 87B). This allows flexibility in orienting the spray 80 onto the tissue 85.
  • the sprayer 16 can be oriented downwardly at an angle directly onto the tissue 85.
  • the sprayer 16 used in the method of the present invention is a compressionless system (no liquid pressure or air pressure)
  • the operability of the sprayer 16 can be maintained despite the incline angle of the sprayer 16 because of the phenomenon at the free end surface 75.
  • the vacuum (negative pressure) created by the low frequency ultrasonic waves at the free end surface 75 of transducer tip 74 are sufficiently strong to pull the droplets 84 of liquid on the side surface 76 to the free end surface 75.
  • This vacuum force overcomes gravitational forces which would ordinarily be expected to pull the droplets 84 on the side surface 76 away from the free end surface 75.
  • the method of the present invention includes orienting the spray upwardly or downwardly onto a tissue while still maintaining forceful projection of the spray without compression of liquid delivered to the free end surface and without air pressure conventionally used to direct a spray.
  • the free end surface 75 of the transducer tip 74 preferably is cylindrical in shape and has a diameter of about 1 centimeter.
  • an intensity of radiation of about 1.5 W/cm 2 is provided over the free end surface 75 to produce ultrasonic waves having an amplitude of about 50 microns. This produces a particle size of the spray of about 5 microns and a spray cone length of about 40 centimeters.
  • a significant bactericidal effect occurs by application of liquids on infected and inflamed tissue, as well as non-biological surfaces, using the method of the present invention.
  • the method produces two bacteria killing effects.
  • the low frequency ultrasonic waves carried to the tissue physically destroy bacteria on the tissue surface 84 and up to 1 millimeter below the tissue surface 85.
  • the ultrasonic waves are believed to cause cavitational and/or microstreaming effects in the bacteria which disrupt the bacteria cells. This effect is maximized when the frequency is from 16 to 40 kilohertz and particularly at 26 kilohertz. However, at least some effect is achieved in the frequency range of 40 kilohertz to 200.
  • the bactericidal and healing effect is about 80 percent of the maximum effect obtained in the range from 16 to 40 kilohertz.
  • a frequency range of 100 to 150 kilohertz used with the method of the present invention achieves an effect about 50 percent of the maximum effect achieved in the frequency range of 16 to 40 kilohertz.
  • a frequency of 16 up to 20 kilohertz can be used, this range is generally avoided because the sound waves may be uncomfortable to the patient and operator.
  • the bactericidal effect results, in part, from the "insonication" of antibiotics in the method of the present invention.
  • Antibiotics "insonified” in the method of the present invention become highly activated and have an increased effectiveness over conventionally applied antibiotics. Accordingly, although the atomized particle spray can be created by delivering the liquid 52 directly to the free end surface 75, it is particularly advantageous to first deliver the liquid 52 to the side surface 76 a predetermined distance (e.g. , D2 in FIG. 3) from the free end surface 75 of the transducer tip 74.
  • the liquid droplets 83 of antibiotic become “insonified”, i.e., highly activated, from vibratory ultrasonic radiation on the side surface 76 of transducer tip 74. Accordingly, because the liquid droplets 84 maintain contact with the transducer tip 74 as they move to the free end surface 75, the droplets 84 of antibiotic remain "insonified", i.e. , highly activated. This activated state is retained as the droplets become particles and are projected from the free end surface 75. However, when the liquid 52 is delivered directly to the free end surface 75 without first being delivered to the side surface 76, the liquid particles lack the "insonification" phenomena of the liquid particles created when the liquid 52 is first delivered to the side surface 76. Insonified antibiotics are highly activated and increase the effectiveness of antibiotics as compared with traditionally applied antibiotics (oral ingestion or direct topical). Accordingly, the method comprises a highly desirable form of drug delivery.
  • the method of the present invention offers an approach that may re-establish use of some traditional antibiotics and establish a method fighting bacteria without antibiotics when necessary.
  • the effect of the method of the present invention in highly activating antibiotics may allow some traditional antibiotics to overcome bacteria which have become resistant to that antibiotic.
  • the low frequency ultrasonic waves applied in the method of the present invention physically destroy bacteria. Bacteria are unlikely to develop a resistance to this treatment.
  • the combination of the highly activated antibiotics and of the low frequency ultrasonic waves in the method of the present invention produce a strong bactericidal effect not found in mere topically applied or orally ingested antibiotics. This combined effect has been shown to dramatically increase the healing of purulent infected wounds.
  • the method of the present invention can also be used in conjunction with systemic antibiotic therapy to provide a more aggressive treatment course.
  • the method can be applied instead of systemic antibiotic therapy in cases where such systemic treatment is ineffective (e.g., superinfections) or where the side effects of systemic antibiotics (nausea, diarrhea, gastro intestinal upset) are to be avoided.
  • systemic antibiotic therapy e.g., superinfections
  • the side effects of systemic antibiotics nausea, diarrhea, gastro intestinal upset
  • the bactericidal effect resulting from the method of the present invention is more effective when the liquids applied include antimicrobials, oxidants, and antibiotics, as well as antiseptics, this bactericidal effect also occurs when the liquid used is distilled water because of the physical effect of the low frequency ultrasonic waves. This is particularly advantageous for patients that have serious allergies to traditional antibiotics or patients that have superinfections from bacteria resistant to the available antibiotics.
  • the method of the present invention results in several effects upon the purulent infected tissue surface of the wound.
  • the method results in a quick separation of dead tissue (tissue detritus) and clears away pus and destructured tissue elements.
  • the method also causes cupation of the suppurative and inflammatory center.
  • the method results in a sharp intensification of cell immunity reaction and stimulates active proliferation of connective tissue, which revascularizes and replaces the wound tissue.
  • Observed effects include an increased quantity of macrophagial and microphagial cells and fiber layers in the connective tissue as well as an increase in collagenous fiber content, elasticity content, and density of the hemocapillary distribution.
  • the method also accelerates granulation and final epithelization in the wound tissue zone. The combination of these effects results in wound healing about one and onehalf to two times as fast as healing resulting from traditional wound treatment (topical dressings and systemic antibiotics).
  • the accelerated healing effect results from a combination of at least three phenomena.
  • the method produces a mechanical scrubbing action on the wound surface because of the low frequency ultrasonic wave energy reaching the wound surface and because the spray particles are forcefully directed into the wound surface by the ultrasonic waves.
  • This mechanical scrubbing action is responsible for the quick separation of the dead tissue, dirt, and destructured elements from the wound. Moreover, this mechanical effect stimulates healthy tissue growth by accelerating the normal healing process of the wound.
  • a combination of the low frequency ultrasonic waves and the insonified medicines i.e. , highly activated by ultrasonic energy destroys the surface bacteria to result in a higher disinfecting property of the insonified medicines as compared to ordinarily applied liquids.
  • the method of the present invention also causes the liquid medication as well as the ultrasonic waves to penetrate the tissue up to 1 millimeter in depth.
  • the cleansing effect can be used to clean surfaces of objects by removing dirt and the bacteria-killing effect can be used to disinfect surfaces by killing bacteria on the surface.
  • a prophylactic effect of the method actively prevents the development of purulent and inflammatory complications of wounds on human tissue.
  • This effect is achieved because the method of the present invention effectively suppresses the virulency and ability to multiply of pathogenic flora (e.g., streptococcus bacteria) on the surface wound.
  • pathogenic flora e.g., streptococcus bacteria
  • This prophylactic effect is particularly significant for surgery in a nonsterile atmosphere such as field use or in less developed countries not having highly sterile operating rooms. In those situations, virtually every surface (human or otherwise) is laden with bacteria. Killing bacteria on the patient and other surfaces is very important.
  • This prophylactic effect of the insonified medicines is particularly effective where the surface wound 87B is a bum wound (thermal, chemical, or electrical).
  • the method provides a prophylactic effect of complications for bums of the first, second, third, and fourth degrees.
  • the wounds can be treated twice a day using the method of the present invention just prior to application of sterile bandages.
  • the sprayed liquid can include a combination of oxidizers, antibiotics, and antimicrobial agents.
  • This prophylactic effect in bum wounds is significant because infection is a major cause of serious illness and death resulting from bum wounds. The problem results from the inability of the open wound to ward off growth of bacteria and the inability of new skin to form to cover the wound surface to limit bacteria growth.
  • This prophylactic effect on suppurative and inflammatory processes is critical in surgical wounds, open fractures, wounds including stab wounds, and bums of all degrees and types (thermal, chemical, and electrical).
  • an open wound e.g., bum, trauma, surgery
  • the method can be applied to any open wound or surface tissue condition accessible to the method of the present invention.
  • the method of the present invention results in a 50 to 70 percent reduction in volume used of antibiotic medicine used as compared with traditional dressing methods.
  • the method also allows for precise dosage of the sprayed liquid.
  • a user can deliver the desired volume of liquid at a desired rate and duration.
  • the ultrasonic radiation imparted onto the liquid media finely atomizes the different compositions to produce a uniform mixture of the different compositions that does not occur in traditional mixing methods of medicines.
  • the method of the present invention provides a method of compressionless non-contact drug delivery.
  • the liquid 52 is not under compression during delivery from the fluid reservoir 38 to the transducer tip 74.
  • the spray 80 is neither created nor directed with a compressed air system found in conventional spray nozzles. Rather, the spray 80 is created solely by the stress produced on the free end surface 75 by the longitudinal ultrasonic waves emanating therefrom.
  • This lack of compression or pressure is important in preserving the energy of ultrasound waves propagating through the atomized spray as well as preserving the highly activated state of the insonified liquids caused by the oscillating transducer tip 74 of the sprayer 16 used in the method of the present invention.
  • This compressionless, non-contact method of the present invention has been proven to destroy bacteria by action of the ultrasonic waves and by highly activating the liquid medicines (e.g., antibiotics) applied to the tissue.
  • the compressionless feature of the method of the present invention has other important advantages.
  • traditional application of liquid medicines e.g., antibiotics
  • spraying methods e.g., aerosol can, compression sprayer
  • aerosol can, compression sprayer produce a ricochet effect of the medicine in which the spray particles from the spray source bounce off the tissue because of the pressure directing the spray.
  • the rebounding spray particles can travel onto an exposed skin surface (e.g., arm, eye) of the technician (applying the spray) or become airborne to be inhaled by the technician.
  • the technician can receive a harmful dose of the medicine through this ricochet effect of traditional aerosol sprayers.
  • the compressionless spray 80 produced in the method of the present invention does not cause the spray particles 82 to ricochet off the tissue to be treated. Rather, in the method of the present invention, the spray particles 82 have sufficient energy to penetrate the tissue yet do not have energy sufficient to rebound off the tissue.
  • the method of the present invention provides a way to produce an aerosol form of medicines for delivery to tissue without using chloroflourocarbons, which are responsible for deterioration of the ozone layer.
  • the sprayer used in the method of the present invention can include modifications of the diameter of the free end surface 75 of the transducer tip 74.
  • the diameter of the transducer tip can range from 1 millimeter to 40 millimeters.
  • a tip of about 1 centimeter diameter is preferred.
  • the power applied to the transducer 22 is regulated so that an intensity of radiation is delivered to the free end surface 75 of the transducer tip 74 at about 1.5 W/cm 2 and the amplitude of ultrasonic waves is preferably about 50 microns.
  • the spray cone length can be adjusted as desired (by regulating the amplitude of ultrasonic waves) to correspond with the optimum distance of separation between the transducer tip and the surface to be treated.
  • One factor in changing the spray cone length is the diameter of the tip 74. Accordingly, a different tip size may be used when attempting to achieve a different spray cone length. In general, smaller diameter tips are preferred when generating a longer spray cone.
  • the primary factor in determining spray cone length is the amplitude of the ultrasonic waves, which can be controlled by the ultrasonic generator.
  • the spray cone length can be affected by the size of atomized particles wherein a larger particle size (e.g., 10 microns) will result in a longer spray cone than a smaller particle size (e.g., 3-5 microns) because the larger particles tend to travel farther.
  • a larger particle size is achieved by increasing the delivery rate of the liquid to the transducer tip. Accordingly, although the diameter of the tip can be varied as desired, it is but one factor in controlling the spray cone length of the spray.
  • the method of the present invention which uses sprayer 16 also can include several modifications.
  • the configuration of the distal end of the sprayer 16 can be modified to affect differences in the spray cone generated by the free end surface 75.
  • by securing the bellmouth 66 about the transducer tip 74 on an interior surface 65 of the second end 30 (as shown in FIGS. 2 and 3) creates a narrower spray cone of the atomized particle spray than would occur without the bellmouth 66 (see also FIG. 6).
  • This permits a user to more precisely direct the particle spray as desired because of the more focused spray cone.
  • this configuration increases the length of the spray cone of the atomized particle spray thereby permitting an increased distance of separation between the transducer tip 74 and tissue to be treated while still maintaining the propagation of ultrasonic waves and delivery of atomized particles.
  • a bellmouth 88 can be fixed on an exterior surface 90 of the second end 30 of the housing 31.
  • the bellmouth 88 encompasses the transducer tip 74 and has an open portion 92 facing outwardly into the ambient environment.
  • the free end surface 75 is disposed concentrically within the bellmouth 88.
  • the free end surface 75 of transducer tip 74 can be modified from a flat surface (FIGS. 2 and 3) to a preferred truncated cone shape as shown in FIG. 8.
  • the free end surface 94 has an inclined side surface 96 extending between the side surface 76 and the free end surface 94. This surface 96 facilitates distribution of the liquid media circumferentially about the periphery of the free end surface 94.
  • the surface 96 allows a greater volume of fluid to be atomized uniformly because of the increased peripheral distribution of the liquid media from side surface 76 of the transducer tip 74 as it descends along surface 96. Accordingly, with this preferred configuration, the liquid media more uniformly approaches the free end surface 94 around the entire edge of the surface 94 as compared to a flat end surface such as free end surface 75 shown in FIGS. 2 and 3.
  • the most preferred configuration includes the truncated cone shape free end surface 94 of the transducer tip in combination with either the bellmouth 66 (FIG. 6) or the bellmouth 88 (FIG. 7) encompassing the transducer tip.
  • These preferred configurations maximize distribution of a liquid onto its free end surface while also minimizing or maximizing a spray cone angle and length as desired.
  • the free end surface 75 can be modified into other surface shapes.
  • FIGS. 9-18 a variety of transducer tips 74 are shown each having a different shaped free end surface.
  • FIG. 9 illustrates a transducer tip 74 having a free end surface 98 in the shape of a concave inclined surface.
  • FIG. 10 illustrates a transducer tip 74 having a free end surface 100 which is inclined relative to the longitudinal axis of the transducer tip 74 yet is relatively flat (as compared to concave free end surface 98 of FIG. 8). This surface 100 facilitates delivery of the liquid in stream form because the surface is tilted toward the source of the stream.
  • FIG. 11 illustrates a transducer tip 74 having a free end surface 102 in the shape of a cone.
  • the cone shaped surface 102 provides a wider angle spray cone, although the width of the spray cone depends on the angle of the cone.
  • FIG. 12 shows a transducer tip 74 having a free end surface 104 in the shape of an ellipsoid of revolution, i.e. , a concave curved surface in the shape of a bowl. This concave shape focuses to ultrasonic waves to a focal point beyond the free end surface 104 to accentuate penetration of the ultrasonic waves below a tissue surface.
  • FIG. 13 illustrates a transducer tip 74 having a free end surface 106 in the shape of a convex hemispherical surface. This surface results in a spray that is more uniform and distributed in a hemispherical shape rather than a cone shape (shown in FIG. 3).
  • FIG. 14 illustrates the transducer tip 74 in its modified form having a free end surface 108 in the shape of a cone having concentrically arranged ring surfaces 110. This surface results in a spray in the form of a spiral for producing a higher pressure spray.
  • FIG. 15 shows a transducer tip 74 having a free end surface 112 having an inclined surface relative to the longitudinal axis of the transducer tip 74 wherein the surface includes a concave curvature and includes ridges 114 on the free end surface 112.
  • FIG. 16 shows a transducer tip 74 having a free end surface 116 that is inclined relative to the longitudinal axis of the transducer tip 74 and further includes a plurality of steps 118 formed in the inclined surface 116.
  • the surfaces 112 (with ridges 114) and 116 (with steps 118) increase the contact time of the liquid with the free end surface to accentuate the insonication of the liquid particles.
  • FIG. 17 shows a transducer tip 74 having a free end surface 120 having a undulating surface shape. This surface produces a mixing of ultrasonic wave characteristics of diffraction, interference, etc.
  • FIG. 18 shows a transducer tip 74 having a free end surface 122 having stepped indentations 124. This surface produces a pulsed-type spray because particles leaving the troughs of the steps 124 have different energy levels than the particles leaving the tops of the steps 124.
  • one of the bellmouth arrangements (66 of FIG. 6 or 88 of FIG. 7) can encompass the transducer tip 74 of one of modified free end surface embodiments in FIGS. 9-18 to further alter the spray cone as desired.
  • the method of the present invention can further include simultaneously or selectively directing multiple liquids to the free end surface of the ultrasonic transducer.
  • FIG. 19 an end sectional view
  • the sprayer 16 of FIG. 2 has been modified so that channels 62B and 62C are provided, in addition to channel 62 A, for delivering a liquid to the side surface 76 and/or free end surface 75. Accordingly, channel 62B directs liquid B to the transducer tip 74 and channel 62C directs liquid C to the transducer tip 74.
  • This arrangement is especially suited for simultaneously delivering liquids (e.g., A, B, C) to the transducer tip 74 where each liquid has a different viscosity so that a uniform mixture of the liquids can be produced at the transducer tip.
  • this arrangement can permit several liquids to be selectively directed to the transducer tip 74 for applying several liquids, one at a time, in series to a tissue surface.
  • the liquid 46 need not be delivered to the top side of the transducer tip 74 (see FIGS. 2 and 3) but rather can be delivered from any direction (e.g., top, side, bottom, etc.) relative to the transducer tip 74 (FIG. 19).
  • FIG. 20 illustrates a modification of the sprayer 16 of FIG. 2 to include delivery of the liquid 52 to the bottom of the transducer tip 74.
  • the modified sprayer housing 31 includes a tube 125, a channel 126, and a pressure bulb 127.
  • the channel 126 extends from the aperture 64 to an opening 128 in the housing 31.
  • One end of the tube 125 is connected to the housing 31 at the opening 128 and a second end 129 of the tube 125 is connected to the bulb 127.
  • the bulb 127 includes a cavity for holding the liquid 52. To deliver the liquid 52, the bulb 127 is squeezed to force the liquid out of the bulb 127 into the tube 125 and through the channel 126.
  • the tube 125 and bulb 127 are configured to deliver the liquid 52 such that liquid 52 arrives at the side surface 76 of the transducer tip 74 with little or no pressure.
  • the liquid is then delivered to the free end surface 75 by the vacuum effect of the ultrasonic waves as previously described in association with FIGS. 2 and 3.
  • This modified configuration of liquid delivery can provide an alternative delivery system to the delivery system 32 as orientation (e.g., vertical, angled) of the sprayer 16 warrants.
  • any medicines or liquids can be applied using the method of the present invention.
  • the type of medicine used depends on the pathology of the disease, its location, and the stage of the suppurative and inflammatory processes on the wound.
  • an antibiotic, antimicrobial, oxidant, and sulfanilamides are applied separately or in combination.
  • Antibiotics, among others, suitable for use in the method of the present invention include ampicillin, sodium salt, microcide, ceporin (u), tetracycline hydrochloride, neomycin sulfate, kanamycin, gentamycin, erythromycin, levomycetin, polymican, M sulfate, gramicidin.
  • Antiseptics suitable for use in the method of the present invention include iodinal, hydrogen peroxide, hydroperie, salicylic acid solution, sodium tethraborate, methylene blue, green brilliantine, ethacridine lactate, chlorhexadine, novoimanine, baliz-2, sanguirythrin, lisozyme, tincture of Japanese sophora.
  • Sulfanilamides suitable for use in the method of the present invention include soluble streptocide, sodium norsulfazole, sulfazine, sodium sulfate, furaplast, furacillin.
  • anti viral medicines include oxolin for treating viral rhinitis.
  • the method of the present invention can be used for spraying other biological surfaces such as an ear, nasal and sinus cavities, oral cavity, vagina, and an eye.
  • some steps of the method are substantially the same as those described for the method already discussed.
  • the steps of providing a liquid, providing a source of low frequency ultrasonic waves, and delivering the liquid to the free end surface of the ultrasonic transducer to create a spray are generally common to all of the methods of the present invention for spraying a surface to kill bacteria and/or deliver a drug.
  • the surface to be sprayed includes the middle ear and external ear.
  • the method is useful in spraying the tympanic membrane (i.e. , ear drum), and the external auditory canal.
  • This condition is very painful, and if not treated, can result in dizziness and partial hearing loss.
  • the condition also results in a suppurative, i.e. , pus-like discharge which can create an offensive odor.
  • the condition typically results from infection and fluid build up in the middle ear when the eustachian tube becomes blocked, preventing fluid drainage from the middle ear.
  • Traditional methods of treatment of the symptoms include mechanical abrasive cleansing of suppuration on the external auditory canal.
  • infections of the middle ear are interior of the tympanic membrane, and therefore require treatment either by systemic antibiotics (i.e., orally ingested) or by making an incision in the tympanic membrane for insertion of a tube through the tympanic membrane.
  • This procedure relieves the painful pressure inside the middle ear (resulting from the infection) by allowing fluid to drain from the ear.
  • the bacteria in the middle ear are treated, the infection can continue after cleaning the external auditory canal and after introducing a tube through the tympanic membrane.
  • systemic antibiotics are not necessarily the first choice of treatment because of the complications of associated with systemic antibiotics (e.g. , nausea, gastrointestinal upset) as well as the possibility of incurring a superinfection when the infection results from a resistant form of bacteria or pathogenic microflora.
  • systemic antibiotics e.g. , nausea, gastrointestinal upset
  • an ear 130 includes an inner surface 132 of an external auditory canal 134.
  • a tympanic membrane 136 is located at the most interior portion of the canal 134.
  • a middle ear 138 including an incus 140, malleus 142, and a stapes 144, is located adjacent to and just interior of the tympanic membrane.
  • Bacteria is typically located in the region of the middle ear 138. Killing bacteria in the ear using the method of the present invention includes providing an antibiotic fluid 52 within fluid reservoir 38 of the sprayer 16.
  • the sprayer 16 is positioned such that the free end surface 75 of the transducer tip 74 is aligned with the external auditory canal 134 of the ear 130 so that the long axis of the transducer tip 74 is substantially parallel with the long axis of the external auditory canal 134.
  • a directed spray 80 of the antibiotic is created and forcefully projected from the free end surface 75 in the manner described for the method of the present invention in association with FIGS. 2-4.
  • This method includes the step of providing a source of low frequency ultrasonic waves and the step of delivering the liquid 46 to the free end surface 75 of the ultrasonic transducer tip 74.
  • the method further includes orienting the spray 80 of antibiotics to enter the ear canal 134 and strike the surfaces 132 along the auditory canal 134 as well as the surface of the tympanic membrane 136.
  • the antibiotic spray particles 82 are propelled by the ultrasonic waves emanating from the free end surface 75 and the spray particles 82 act as a medium (in combination with the ambient air) for carrying the ultrasonic waves into the tissue of the auditory canal 134 and for penetration into the tympanic membrane 136 up to 1 millimeter in depth.
  • a continuous spray can be applied within the external auditory canal 134 for about 30 to 60 seconds and up to five minutes, or for whatever duration and frequency deemed necessary by a user of the device.
  • this treatment can be given once a day for several days in a row (e.g., three days to two weeks).
  • a distance of separation of about 1 to 10 centimeters can be preferably maintained between the tympanic membrane 136 and the free end surface 75 of the transducer tip 74 during the step of orienting the spray 80 onto the respective tissue surfaces.
  • the method of the present invention for killing bacteria within an ear enjoys the same advantages and effects as described earlier in association with FIGS. 2-4 for the general method of the present invention for killing bacteria on a wound surface or non-biological surface.
  • the insonified (i.e., highly activated) antibiotics of liquid 52 of the particle spray 80 and the low frequency ultrasonic waves penetrate the tympanic membrane 136 and surface 132 of the external auditory canal 134 to actively disrupt and destroy the bacteria cells on and within the tissue.
  • the method can be used to kill bacteria on other surfaces of the body including the nose, eyes, mouth, and vagina.
  • Bioptate was followed.
  • the method of the present invention was applied using a frequency of ultrasonic waves of 26.5 +/- 1 IriloHertz. This frequency is thought to maximize cavitational effects that disrupt bacterial cells.
  • the ultrasonic generator 12 was operated to test ultrasonic wave oscillation amplitudes of 10, 30, 60, 80 and 100 microns. Treatment times included durations of continuous spraying for 30 seconds, 60 seconds, 3 minutes, 5 minutes, and 10 minutes.
  • Purulent infected wounds with varying area and depth were modeled in the animals in the upper third of the thigh. Treatment was conducted by the generally accepted methods in the control group. The animals in the control group received massive doses of broad-spectrum antibiotics and sulfanilamides. Oxidants and antimicrobial preparations were applied locally to the infected surface. The infected surface was also regularly washed with hydrogen peroxide, furacillin, permanganate, and was sprinkled with antibiotics, novamine, baliz-2 and other conventional preparations. Sterile dressings were applied and the wound was drained.
  • the purulent infected wound was treated with a liquid aerosol of the medicinal preparations (oxidants, antibiotics, antimicrobials).
  • the medications were applied, using the method of the present invention, to the wound surfaces twice per day with a distance of separation between the transducer tip and the wound surface being 4 to 7 centimeters.
  • the duration of treatment time was 30-60 seconds.
  • microbial flora were obtained from the wound and histologic monitoring of the regenerative processes was performed. Biochemical and cytochemical monitoring of the immune status of the peripheral blood of the experimental animals was also performed.
  • This time period (12 to 15 days) includes the time of cleansing of the wound of tissue detritus, regeneration of the juvenile connective tissue and epithelialization of the wound surface.
  • the time required for complete healing of the infected wound was reduced by a factor of 2-2.5 in comparison with the control series of experiments, in which the treatment of the purulent inflammatory focus was performed by traditional methods.
  • Microbiological monitoring of the condition of the pathogenic flora Streptococcus aureus
  • Pseudomonas pyocyanea, Bacillus coli, etc. screened from the purulent inflammatory focus showed that the preparations insonified with low-frequency ultrasound in the method of the present invention suppress their virulence, i.e. , their ability to reproduce.
  • the method of treatment of the present invention was applied to human patients having purulent infected wounds.
  • Treatment of wounds using the method of the present invention was performed on patients with various diagnoses, such as extensive bacteria laden infected wounds of the lower leg, foot and hand, and also wounds following trauma or surgery which failed to heal over a considerable time.
  • Treatment of purulent infected wounds was performed using the method of the present invention as previously described in association with FIGS. 2-4.
  • the duration of treatment was 30 seconds to five minutes and a course of treatment consisted of up to 5 sessions, depending on the condition of the wound and the progress of the healing process, as determined by a physician using the method.
  • the results were evaluated on the basis of the clinical and bacteriological data (see Table 1.1).
  • the bacteriological analysis was performed before and after each ultrasonic treatment session of a purulent wound.
  • the qualitative and quantitative composition of the microflora was determined.
  • the quantitative composition of the microflora (number of microbial cells in 1 g of tissue) was determined in a bioptate (i.e., biopsy) obtained from the wound of a patient.
  • the results of determination of the qualitative and quantitative composition of the microflora in the wounds are presented in Table 4.1.
  • ultrasound treatment using the method of the present invention was applied to purulent wounds having post-traumatic osteomyelitis developing after open fractures.
  • the method of the present invention was applied to purulent wounds on patients during changing of dressings.
  • the medicines used included 0.2% solutions of chlorhexine, or an antibiotic to which the microflora of the wound were sensitive.
  • the entire surface of the wound was treated, as well as the surface surrounding a fistula.
  • One to five treatments were applied, depending on the size, nature of the wound and the purulent discharge.
  • the volume of solution used varied between 50 to 100 ml of solution.
  • the total number of bacteria per gram of tissue taken from deep wounds was 1 ⁇ 10 6 to 1 ⁇ 10 9 microbes in 13 patients, which is higher than the critical level.
  • 1 ⁇ 10 5 microbes (within the critical level) were found in the wound tissue and in another patient, 1 ⁇ 10 4 microbes were found, which is below the critical level.
  • the bacteriological analysis showed that in 4 cases, the gram-positive diplococci found prior to application of ultrasound by the method of the present invention were absent in the bacteriological samples after treatment of the wound (case histories No. 8064, 10816, 1202, 9173).
  • a group of pathogens was found (Staphylococcus St. aureus and Pseudomonas aeruginosa) in samples of purulent material prior to treatment and that, after treatment with the method of the present invention, bacteriological studies continued to produce Ps. aeruginosa. This may be related to its high resistance to antibiotics and antiseptics (case history No. 10816). The samples were negative.
  • the quantitative composition of the microflora in 15 infected patients was compared before and during treatment with the method of the present invention. It was found that prior to treatment, each gram of bioptate of wound tissue contained from 1.0 ⁇ 10 6 to 1.0 ⁇ 10 9 microbial cells. However, after treatment with the method of the present invention, the number of microflora in the bioptate of the purulent wounds (with combined treatment) dropped to 1.0 ⁇ 10 5 , or less than the critical threshold in 67% of the total number of patients (in 10 cases). In the remaining 33% of the total number of patients (in 5 cases), the number of microflora fell to 1.0 ⁇ 10 6 to 1 ⁇ 10 7 as found in the bioptates of the wound tissue.
  • the microbiological study data was consonant with the observed clinical course of the wound process.
  • the wounds were cleansed of necrotic tissue, edema was reduced, discharges were slight or stopped entirely, and granulation was seen.
  • the wounds were clean, decreased in size, rapid epithelialization was under way, fistulas had closed, and there was no discharge.
  • One-time treatment of the wound with the method of the present invention for 1-5 minutes yielded no significant reduction in the number of microflora per gram of tissue, but did cause mechanical cleansing of the wound of detritus and clots of blood and removal of necrotic masses. About 5-6 hours following treatment, the patients reported mild itching in the wound and surrounding area. After repeated treatment, the wound was further cleaned of fibrinous-purulent encrustation and necrotic tissue. Bacterial contamination was reduced by 2-6 orders of magnitude. With one or two treatments of low-frequency ultrasound using the method of the present invention, the wounds became clean and active granulation was observed.
  • Subsequent treatment of purulent wounds with the method of the present invention also facilitated appearance of strong granulation, a reduction in inflammatory infiltrate and complete healing of the wound. It was not possible to collect a bioptate from the depth of the wound after the 4th or 5th treatment because the healing of the wound had progressed sufficiently and the wound was covered by granulation tissue.
  • Patient number 5 entered the Clinical Emergency Hospital with the following diagnosis: "Extensive scalped wound of the lower third of the right calf, posterior surface and foot, with compression of the soft tissue of the calf. Marginal fracture of the malleolus, no displacement. " This trauma was received by the patient in an automobile accident. The wound was infected and the size of the wound surface was 2010 cm 2 .
  • the bioptate of the extensive purulent wound yielded Pseudomonas aeruginosa having 7.2 ⁇ 10 6 microbe cells per gram of tissue.
  • Pseudomonas aeruginosa remained but its quantity per gram of bioptate dropped to 24 ⁇ 10 4 microbe cells. This level is below the critical level by 2 orders of magnitude.
  • the wound was cleansed of purulent-necrotic masses, swelling was decreased, mild granulation had started.
  • purulent discharge was stopped, clear granulation was evident, and the wound had decreased in size. After complete healing of the wound patient V-a received plastic surgery of the skin.
  • microbiological studies showed that prior to treatment with the method of the present invention with combined treatment of purulent wounds, the bacteria Proteus (4), Klebsiella (2), Ps. aeruginosa (1), Staphylococcus St. epidermidis (2) and gram-positive diplococci were present in monocultures. In the remaining cases, microflora were found in association.
  • the wounds were cleansed of pus and necrotic masses, discharges decreased.
  • the microflora were found to remain present and to basically have the same qualitative composition as earlier. Only in two cases were associations of cultures (gram- positive diplococci and Ps. aeruginosa) replaced by monocultures of Ps. aeruginosa (case history No. 6678 and No. 4441).
  • Staphylococcus Staphylococcus (St. aureus, St. epidermidis) Pseudomonas.aeruginosa, E. coli and others in monoculture.
  • the number of microbes per gram of tissue in 9 patients was 1 ⁇ 10 6 to 1 ⁇ 10 8 cells, higher than the critical level.
  • the content of microbes per gram of tissue dropped by only 1-2 orders of magnitude in the process of treatment.
  • bacteriological study of the bioptates and cultures in patients with purulent-inflammatory processes before use of ultrasound in the method of the present invention showed that the leaders among pathogens in the purulent foci were staphylococci (St. aureus and St. epidermidis), representing 31.6% (18) cultures, Pseudomonas aeruginosa, representing 26.3% (15) cultures, while 42.1 % (24) cultures consisted of accompanying microflora (gram-positive diplococci, gram-negative bacilli, diphtheroids, etc.).
  • Staphylococcus aureus appeared in monoculture and in 62% (5) Staphylococcus aureus appeared in association with other microorganisms.
  • Staphylococcus epidermidis was cultured in 60% (6) of the cultures in monoculture and in 40% (4) in association with other microflora including: Staphylococcus aureus in 17% (10) cultures, Pseudomonas aeruginosa in 40% (6) cultures in monoculture and in 60% (9) in associations.
  • Antibiotic-response diagrams were produced for the microorganisms found with 20 antibiotics: neomycin, heptamycin, rifampicin, penicillin, ampicillin, erythromycin, monomycin, polymyxin, streptomycin, lincomycin, carbenicillin, kanamycin, methicillin, oxacillin, oleandomycin, tetracycline, fusidine, levomycetin, ristamycin and dococycline.
  • the antibiotic-response diagrams showed that thirteen strains of microbes were monoresistent (sensitive to a single antibiotic), amounting to 22% of the total. Seven strains were sensitive to two antibiotics (12%), four strains were sensitive to three antibiotics (17%), two strains each were sensitive to six and eight antibiotics (3% each), and 1 strain each of microbes showed sensitivity to 4, 5, 10, 11, 12 and 18 antibiotics (1 % each).
  • strains obtained from the pumlent wounds 21 strains of microorganisms were sensitive to 20 antibiotics, which amount to 37%.
  • FIG. 26 illustrates a healthy bacteria cell, Pseudomonas
  • the photograph of FIG. 26 is an image of a bacteria cell at 50,000 times magnification obtained with a scanning electron microscope.
  • the bacteria cell was taken from a bioptate of a wound of a patient and then mounted on a viewing medium. This single bacteria cell was separated from other bacteria in the bioptate of the wound.
  • the bacteria cell includes a body portion with whiplike organelles extending from the body portion for securing the bacteria cell to a surface, e.g., tissue.
  • FIG. 27 illustrates that the bacteria cell (at 50,000 times magnification) has lost its organelles, has begun to bulge, and has become much shorter and wider after treatment with the method of the present invention.
  • the bacteria cell was treated about another fifteen seconds with the method of the present invention with the result shown in FIG. 28 (50,000 times magnification).
  • the bacteria cell has shrunk even further. More importantly, the bulges shown in FIG. 27 have been punctured such that the contents of the cell are forced outside the cell causing death of the bacteria cell. As part of this destruction, the cell wall has separated from the contents of the cell also effectively killing the cell.
  • FIG. 29 illustrates a colony of bacteria cells at 15,000 times magnification (by a scanning electron microscope) after treatment with the method of the present invention.
  • the duration of treatment was approximately 60 seconds.
  • Each cell in FIG. 29 has reached the state of puncture and expulsion of some cell contents as well as separation of the cell wall from the cell contents.

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  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Anesthesiology (AREA)
  • Engineering & Computer Science (AREA)
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  • Rehabilitation Therapy (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

L'invention concerne un procédé de pulvérisation sur un tissu humain avec un transducteur ultrasonique (70) produisant des ondes ultrasoniques basse fréquence. Le transducteur a une extrémité (74) avec un surface d'extrémité libre (75) exposée à l'environnement ambiant. Le liquide atomisé est projeté par les ondes ultrasoniques et les particules dispersées fournissent un support permettant la propagation des ondes ultrasoniques générées sur la surface d'extrémité libre. Les particules dispersées sont dirigées directement sur la surface à traiter, en conservant une certaine distance entre la surface à traiter et la surface d'extrémité libre du transducteur.
PCT/US1995/014926 1995-11-15 1995-11-15 Procede de pulverisation sur une surface, en utilisant des ultrasons WO1997017933A1 (fr)

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PCT/US1995/014926 WO1997017933A1 (fr) 1995-11-15 1995-11-15 Procede de pulverisation sur une surface, en utilisant des ultrasons
AU42380/96A AU4238096A (en) 1995-11-15 1995-11-15 Method of spraying a surface using ultrasonic radiation

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Cited By (19)

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WO2002024150A2 (fr) 2000-09-25 2002-03-28 Advanced Medical Applications, Inc. Procede et dispositif a ultra-sons utilises dans le traitement des lesions
WO2002085456A1 (fr) * 2001-04-23 2002-10-31 Celleration Procede et dispositif a ultrasons conçus pour le traitement des lesions
EP1436028A2 (fr) * 2001-09-12 2004-07-14 Ivax Corporation Nebuliseur ultrasonore facilitant la respiration et ampoule de dose unitaire associee
WO2004085079A1 (fr) * 2003-03-27 2004-10-07 Unilever Plc Production d'aerosol a partir d'une surface vibrante
EP1624938A1 (fr) * 2003-05-20 2006-02-15 James F. Collins Systeme de distribution de medicaments ophtalmiques
WO2007021427A2 (fr) 2005-08-16 2007-02-22 Babaev Eilaz P Appareil ultrasonore et methodes pour melanger des liquides et pour enrober des stents
WO2008042669A1 (fr) * 2006-09-29 2008-04-10 Eilaz Babaev Dispositif ultrasonique d'administration de liquides et procédés d'utilisation de l'énergie ultrasonique pour administrer des liquides dans le corps
WO2009011715A1 (fr) * 2007-07-13 2009-01-22 Eilaz Babaev Méthode de traitement de blessures par élaboration d'une solution thérapeutique avec des ondes ultrasonores
WO2009102976A3 (fr) * 2008-02-15 2009-11-12 Timothy Sean Immel Dispositif de traitement par aérosol à administration haute fréquence
US7830070B2 (en) 2008-02-12 2010-11-09 Bacoustics, Llc Ultrasound atomization system
US7842249B2 (en) 2006-03-29 2010-11-30 Bacoustics, Llc Apparatus for vaccine development using ultrasound technology
US7846341B2 (en) 2006-12-04 2010-12-07 Bacoustics, Llc Method of ultrasonically treating a continuous flow of fluid
US7896854B2 (en) 2007-07-13 2011-03-01 Bacoustics, Llc Method of treating wounds by creating a therapeutic solution with ultrasonic waves
US8016208B2 (en) 2008-02-08 2011-09-13 Bacoustics, Llc Echoing ultrasound atomization and mixing system
US8050752B2 (en) 2006-09-29 2011-11-01 Bacoustics, Llc Method of treating lumens, cavities, and tissues of the body with an ultrasound delivered liquid
US8449493B2 (en) 2008-01-18 2013-05-28 Eilaz Babaev Ultrasonic syringe method
EP3287113A1 (fr) 2006-01-23 2018-02-28 KCI Licensing, Inc. Système de traitement de plaie par débridement par ultrasons
US10149826B2 (en) * 2015-01-20 2018-12-11 Hyalo Technologies, LLC Method of preparing microspheres
US10383646B2 (en) 2008-12-16 2019-08-20 Sanovas Intellectual Property, Llc Methods and systems for delivery of acoustic energy to tissue surfaces, cavities and obstructed passages such as intranasal ostia

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Cited By (33)

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Publication number Priority date Publication date Assignee Title
EP1322275A2 (fr) * 2000-09-25 2003-07-02 Advanced Medical Applications Inc. Procede et dispositif a ultra-sons utilises dans le traitement des lesions
EP1322275A4 (fr) * 2000-09-25 2004-10-27 Advanced Medical Applic Inc Procede et dispositif a ultra-sons utilises dans le traitement des lesions
JP2005520574A (ja) * 2000-09-25 2005-07-14 アドバンスト メディカル アプリケーションズ インコーポレーテッド 創傷治療用超音波方法及び装置
WO2002024150A2 (fr) 2000-09-25 2002-03-28 Advanced Medical Applications, Inc. Procede et dispositif a ultra-sons utilises dans le traitement des lesions
WO2002085456A1 (fr) * 2001-04-23 2002-10-31 Celleration Procede et dispositif a ultrasons conçus pour le traitement des lesions
EP1436028A2 (fr) * 2001-09-12 2004-07-14 Ivax Corporation Nebuliseur ultrasonore facilitant la respiration et ampoule de dose unitaire associee
EP1436028A4 (fr) * 2001-09-12 2007-04-04 Ivax U K Ltd Nebuliseur ultrasonore facilitant la respiration et ampoule de dose unitaire associee
WO2004085079A1 (fr) * 2003-03-27 2004-10-07 Unilever Plc Production d'aerosol a partir d'une surface vibrante
US8936021B2 (en) 2003-05-20 2015-01-20 Optimyst Systems, Inc. Ophthalmic fluid delivery system
EP1624938A1 (fr) * 2003-05-20 2006-02-15 James F. Collins Systeme de distribution de medicaments ophtalmiques
EP1624938A4 (fr) * 2003-05-20 2009-04-01 James F Collins Systeme de distribution de medicaments ophtalmiques
EP1915218A4 (fr) * 2005-08-16 2008-09-03 Eilaz P Babaev Appareil ultrasonore et methodes pour melanger des liquides et pour enrober des stents
WO2007021427A2 (fr) 2005-08-16 2007-02-22 Babaev Eilaz P Appareil ultrasonore et methodes pour melanger des liquides et pour enrober des stents
JP2009504396A (ja) * 2005-08-16 2009-02-05 ババエヴ，エイラズ，ピー． 液体を混合してステントを被覆する超音波装置及び方法
EP1915218A2 (fr) * 2005-08-16 2008-04-30 Eilaz P. Babaev Appareil ultrasonore et methodes pour melanger des liquides et pour enrober des stents
EP3616669A1 (fr) 2006-01-23 2020-03-04 KCI Licensing, Inc. Système de traitement d'une blessure par débridement ultrasonique
EP3287113A1 (fr) 2006-01-23 2018-02-28 KCI Licensing, Inc. Système de traitement de plaie par débridement par ultrasons
US7943352B2 (en) 2006-03-29 2011-05-17 Bacoustics, Llc Apparatus and methods for vaccine development using ultrasound technology
US7842249B2 (en) 2006-03-29 2010-11-30 Bacoustics, Llc Apparatus for vaccine development using ultrasound technology
WO2008042669A1 (fr) * 2006-09-29 2008-04-10 Eilaz Babaev Dispositif ultrasonique d'administration de liquides et procédés d'utilisation de l'énergie ultrasonique pour administrer des liquides dans le corps
US8050752B2 (en) 2006-09-29 2011-11-01 Bacoustics, Llc Method of treating lumens, cavities, and tissues of the body with an ultrasound delivered liquid
US7846341B2 (en) 2006-12-04 2010-12-07 Bacoustics, Llc Method of ultrasonically treating a continuous flow of fluid
US7896854B2 (en) 2007-07-13 2011-03-01 Bacoustics, Llc Method of treating wounds by creating a therapeutic solution with ultrasonic waves
US7896855B2 (en) 2007-07-13 2011-03-01 Bacoustics, Llc Method of treating wounds by creating a therapeutic combination with ultrasonic waves
US7901388B2 (en) 2007-07-13 2011-03-08 Bacoustics, Llc Method of treating wounds by creating a therapeutic solution with ultrasonic waves
WO2009011715A1 (fr) * 2007-07-13 2009-01-22 Eilaz Babaev Méthode de traitement de blessures par élaboration d'une solution thérapeutique avec des ondes ultrasonores
US8449493B2 (en) 2008-01-18 2013-05-28 Eilaz Babaev Ultrasonic syringe method
US8016208B2 (en) 2008-02-08 2011-09-13 Bacoustics, Llc Echoing ultrasound atomization and mixing system
US7830070B2 (en) 2008-02-12 2010-11-09 Bacoustics, Llc Ultrasound atomization system
US8899230B2 (en) 2008-02-15 2014-12-02 Nasologix, Inc. Aerosol therapy device with high frequency delivery
WO2009102976A3 (fr) * 2008-02-15 2009-11-12 Timothy Sean Immel Dispositif de traitement par aérosol à administration haute fréquence
US10383646B2 (en) 2008-12-16 2019-08-20 Sanovas Intellectual Property, Llc Methods and systems for delivery of acoustic energy to tissue surfaces, cavities and obstructed passages such as intranasal ostia
US10149826B2 (en) * 2015-01-20 2018-12-11 Hyalo Technologies, LLC Method of preparing microspheres

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