AU2003254386C1

AU2003254386C1 - Nebulizing and drug delivery device

Info

Publication number: AU2003254386C1
Application number: AU2003254386A
Authority: AU
Inventors: Vladimir Lvovich Sheiman
Original assignee: Sheiman Ultrasonic Research Foundation Pty Ltd
Current assignee: Sheiman Ultrasonic Research Foundation Pty Ltd
Priority date: 2002-08-23
Filing date: 2003-08-25
Publication date: 2013-11-07
Anticipated expiration: 2023-08-25
Also published as: AU2003254386B2; AU2003254386A2; AU2003254386A1

Abstract

The invention relates generally to a nebulizer, for example, of ultrasonic nebulizer (30) having a bowl shaped container (12) and a tubular energy transmitter in the form of acoustic transmitter pipe (34). One end of the acoustic transmitter pipe (34) is immersed in the liquid (14) of the container (12). The bowl shaped ultrasonic transducer (16) is operatively coupled to the bowl shaped container (12) for transmission of ultrasonic energy to the liquid (14) and acoustic transmitter pipe (34). Absorption of transmitted energy by the liquid (14) forces the liquid (14) toward an upper end of the acoustic transmitter pipe (34) where it is nebulized in the form of an aerosol. The invention also relates generally to a device and method for delivering a substance in an aerosol form into a cellular organism, and a hand held device for delivering a substance to a cellular organism.

Description

1 Ultrasonic Nebulizer Field of the Invention The present invention relates broadly to a nebulizer, and in particular an ultrasonic 5 nebulizer. Background to the Invention There are two main classes of ultrasonic nebulizers, namely those having a flat transducer and others with a concave transducer. This division results in two respective atomisation types being layer atomisation, and fountain atomisation. The delivery rate in 10 layer atomisation is not affected greatly by liquid level. On the other hand, the delivery rate in fountain atomisation depends significantly on the liquid level. It is generally recognised that by setting the liquid level in the vicinity of the ultrasonic focal point, where acoustic intensity is the highest, this results in formation of a fountain originating from the focal point. Usually, during atomisation the liquid level 15 gradually drops until it is below the focal point where the acoustic intensity is not as high. As a result the fountain and all related phenomena (including delivery rate) degrade. At some point, when ultrasonic energy is not sufficient, atomisation stops all together. The mechanism of fountain atomisation is preferred and recognised as more efficient than layer atomisation. As an example, the applicant's US patent 5,908,158 20 describes a nebulizer of this type where the aerosol transportation is assisted by the kinetic energy of the fountain. However, this nebulizer of the prior art has the following shortcomings: i) maintaining the liquid level constant; and ii) excessive aerosol condensation inside the device. 25 Summary of the Invention According to one aspect of the present invention there is provided a nebulizer comprising: a container adapted to contain a liquid to be nebulized; a tubular energy transmitter having one end immersed in the liquid proximate the 2 container; and an energy source being operatively coupled to the container for nebulization of the liquid and being configured for transmission of energy to a focal region of the liquid which is forced toward an opposite end of the tubular energy transmitter. 5 Preferably the energy source is positioned below the container. Preferably the tubular energy transmitter is positioned so that said one end is proximate the bottom of the container. Preferably the tubular energy transmitter vibrates at a frequency to form an aerosol proximate the opposite end of the energy transmitter. 10 Preferably the nebulizer further comprises an aerosol tube positioned about at least a portion of the tubular energy transmitter and having a cross-sectional area such that the positive pressure of the aerosol within the aerosol tube induces a pressure drop within the aerosol tube which propels the aerosol through the aerosol tube. More preferably an internal diameter of the aerosol tube is greater than an internal diameter 15 of the tubular energy transmitter at its opposite end. Even more preferably the aerosol tube is positioned so that it is substantially coaxial with the tubular energy transmitter. Preferably the aerosol tube is connected to the opposite end of the tubular energy transmitter. More preferably the energy source vibrates the liquid proximate the opposite end of the tubular energy transmitter. 20 Preferably the aerosol tube opens at its upper end into an expansion chamber which in turn communicates with an outlet duct. More preferably the expansion chamber is adapted to recirculate larger drops of the liquid back into the container. Preferably the energy source comprises an ultrasonic transducer for transmission of ultrasonic radiation energy. More preferably the ultrasonic transducer has a concave 25 shaped surface. Preferably the ultrasonic transducer is arranged to transmit ultrasonic energy to a focal region of the liquid. More preferably the one end of the tubular energy transmitter is proximate the focal region. Still more preferably an internal diameter of the tubular energy transmitter is substantially equal to a diameter of the focal region.

3 Preferably the tubular energy transmitter has a higher acoustic impedance than the liquid. More preferably the acoustic impedance of the tubular energy transmitter is high enough to effect minimal acoustic energy loss during transmittal of the energy along the tubular energy transmitter. 5 Brief Description of the Drawings A preferred embodiment of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which: Figure 1 is a schematic side elevational view of part of an ultrasonic nebulizer disclosed in the applicant's US patent; 10 Figure 2 is a schematic side elevational view of part of one example of an ultrasonic nebulizer of the present invention which has an ultrasonic transducer positioned beneath liquid which is contained in the nebulizer; Figure 3 is a schematic side elevational view of part of another example of a nebulizer of the present invention having an ultrasonic transducer positioned above liquid 15 contained in the ultrasonic nebulizer; and Figure 4 is a schematic side elevational view of a third example of an ultrasonic nebulizer of the present invention. Detailed Description of the Preferred Embodiment US patent No. 5908158 discloses the applicant's ultrasonic nebulizers which are 20 predecessors to the preferred form of nebulizer of the present invention. The contents of US 5908158 are hereby incorporated into this specification. Figure 1 is a schematic representation of the nebulizer of US 5908158. The nebulizer 10 includes a container in the form of bowl shaped container 12 which contains liquid 14, an energy source in the form of bowl shaped ultrasonic transducer 16 and an aerosol tube 18. The bowl shaped ultrasonic 25 transducer 16 is designed to focus emitted ultrasonic radiation energy at an acoustic focal region, in this example acoustic focal point 20, which is located just beneath an upper surface of the liquid 14. Energy absorbed at the acoustic focal point 20 by the liquid 14 causes liquid to project upwardly to form a liquid spout 22.

4 In addition to formation of the liquid spout 22, ultrasonic radiation focussed at the acoustic focal point 20 results in transmission of acoustic energy upwardly through the liquid spout 22. The acoustic energy within the liquid spout 22 results in nebulization of liquid molecules and the subsequent formation of aerosol 26. Aerosol formation is 5 understood to occur by a process which most likely involves capillary wave and cavitation mechanisms involving high frequency vibrations. The liquid 14 can be a liquid or liquid suspension form of any substance which is required in an aerosol form. For example, the liquid 14 could include a medicated substance, for example a drug, or alternatively could be a perfume. The aerosol 26 is a 10 vaporised form of the liquid 14 and can be administered to a patient, for example, by inhalation. The aerosol 26 is administered to a patient by propelling it upwardly through the aerosol tube 18 which corresponds to the intake tube of the applicant's US patent No. 5908158. As the liquid 14 is nebulized by the nebulizer 10 and aerosol 26 is formed above the 15 liquid 14, this nebulization of the substance results in depletion of the volume of liquid 14 which is contained by the bowl shaped container 12. As the volume of liquid 14 decreases the upper surface 15 of the liquid 14 moves downwardly. Once the upper surface 15 moves below the acoustic focal point 20 the rate of conversion of liquid 14 to aerosol 26 significantly reduces to cause a corresponding reduction in efficiency of operation of the 20 nebulizer 10. Figure 2 shows one example of an ultrasonic nebulizer 30 of the present invention. For ease of reference like features of this ultrasonic nebulizer 30 and the previously described nebulizer 10 are referenced by common reference numerals. The ultrasonic nebulizer 30 includes a bowl shaped container 12 which contains liquid 14 having an upper 25 surface 15, a bowl shaped ultrasonic transducer 16 and an aerosol tube 18. The ultrasonic nebulizer 30 also includes ultrasonic transmission media 32 for instance in the form of water which is positioned between the bowl shaped ultrasonic transducer 16 and the bottom of the nebulized liquid. The separation of the transmission media from the nebulized liquid is made with a thin film 31 which extends across the container 12. The 30 method of separation is not limited by this design. The nebulizer 30 also includes a tubular energy transmitter in the form of an acoustic transmitter pipe 34 which is supported by the aerosol tube 18 via a connection plate which in this example is an annular disc 36. The 5 acoustic transmitter pipe 34 is cylindrical in shape however the tubular energy transmitter is not limited to this shape. The transmitter pipe 34 and the aerosol tube 18 are arranged coaxial with one another. The annular disc 36 includes apertures 38. The bowl shaped ultrasonic transducer 16 focuses ultrasonic radiation at acoustic focal point 40 which is just 5 above the bottom of the liquid 14 but below a lower end of the acoustic transmitter pipe 34. Absorption of ultrasonic radiation energy by liquid 14 at the acoustic focal point 40 forces liquid upwardly through the acoustic transmitter pipe 34 to form a guided liquid spout 44. The guided liquid spout 44 extends beyond an upper surface of the acoustic transmitter pipe 34 and the annular disc 36 as shown in figure 2. Energy imparted to the 10 liquid 14 at the acoustic focal point 40 results in transmission of acoustic energy upwardly through the guided liquid spout 44 and the wall of the acoustic transmitter pipe 34. The presence of acoustic energy at an upper surface 46 of the acoustic transmitter pipe 34, and the guided liquid spout 44, result in the formation of aerosol. All liquid, which is below the upper surface 46 of the transmitter pipe 34 will progressively flow to the entrance of the 15 pipe 34 into the focal zone 40. Under the influence of high power acoustical radiation in the focal zone 40, the liquid is pumped up to the upper surface 46 of the pipe 34. The distance between the entrance of the transmitter pipe 34 and the bottom of the separation film 31 is relatively small. This means that the residual of the nebulized liquid will be considerably reduced because the volume of liquid below the entrance of the pipe 34 is 20 minimised. Delivery of aerosol 26 formed by the ultrasonic nebulizer 30 to a patient treatment site (not shown) is as explained above in relation to the nebulizer 1O.The acoustic impedance of the acoustic transmitter pipe 34 is higher than that of the liquid 14 to prevent radiation dispersing from the acoustic transmitter pipe 34 during transmittal along it. The acoustic impedance is high enough to effect minimal acoustic energy loss during 25 transmission of the ultrasonic radiation. Figure 3 shows an example of a radially spaced energy source in the form of an ultrasonic transducer 56 which encircles a longitudinal mid segment 58 of a tubular energy transmitter in the form of an acoustic transmitter pipe 60. The ultrasonic transducer 56 and acoustic transmitter pipe 60 can be substituted for the ultrasonic transducer 16, ultrasonic 30 transmission media 32 and acoustic transmitter pipe 34 of the ultrasonic nebulizer 30 to form ultrasonic nebulizer 54. The ultrasonic transducer 56 transmits ultrasonic radiation energy directly to the acoustic transmitter pipe 60 and the liquid 14. Ultrasonic radiation 6 energy absorbed by the liquid 14 results in the liquid14 being forced upwardly through the acoustic transmitter pipe 60 to form a guided liquid spout 44. The mechanism which is understood to be responsible for formation of the guided liquid spout 44 is known as the sonocapillary effect. Energy imparted to the acoustic transmitter pipe 60 is transmitted 5 upwardly along walls of the acoustic transmitter pipe 60 as explained above in relation to the acoustic transmitter pipe 34. Liquid is nebulized as explained above in relation to the ultrasonic nebulizer 30 by interaction of the acoustic energy with the liquid spout and upper surfaces of the acoustic transmitter pipe 60. Referring to figure 4, an ultrasonic nebulizer 80 is described using reference 10 numerals of the nebulizer 10 of figure 1 and ultrasonic nebulizers 30 and 54 of figures 2 and 3, respectively, to describe common features. The ultrasonic nebulizer 80 includes a bowl shaped container 12 which contains liquid 14, a bowl shaped ultrasonic transducer 16, ultrasonic transmission media 32 for transmission of ultrasonic radiation emitted by the bowl shaped ultrasonic transducer 16 to the liquid 14. The ultrasonic nebulizer 80 also 15 includes an acoustic transmitter pipe 82 which is similar to the acoustic transmitter pipe 34 of the ultrasonic nebulizer 30. Ultrasonic radiation emitted by the bowl shaped ultrasonic transducer 16 is focused to an acoustic focal point 40 as described above in relation to the ultrasonic nebulizer 30. Aerosol 26 is formed at an upper end 87 of the acoustic transmitter pipe 82 also as described above in relation to the ultrasonic nebulizer 30. 20 The ultrasonic nebulizer 80 differs from examples of ultrasonic nebulizers 30 and 54 described above in that it includes an expansion chamber which in this example is expansion chamber 86. Expansion chamber 86 includes an outlet duct in the form of outlet pipe 88. The outlet pipe 88 is partitioned from the acoustic transmitter pipe 82 by an upright partition wall 90 which is positioned to one side of the expansion chamber 86 to 25 form a main compartment 92 which is positioned directly over the acoustic transmitter pipe 82 so that the acoustic transmitter pipe 82 is approximately aligned with an upright longitudinal axis of the main compartment 92. The partitioned wall 90 also forms a side compartment 94 which connects to a side compartment drain pipe 96 or hole (not shown) that extends downwardly into the liquid 14 of the bowl shaped container 12. 30 The aerosol 26 is produced in the vicinity of the upper end 87 of the acoustic transmitter pipe 82. It is understood that the aerosol 26 is produced from the walls of the guided liquid spout 44 that is moving through the pipe 82 at several meters per second.

7 The aerosol 26 is therefore transported to the user by positive pressure derived intrinsically from the kinetic energy of the spout 44. Nebulization of the liquid 14 provides two components namely the aerosol 26 and a non-nebulized liquid part of the spout 44. The non-nebulized part of the spout 44 is 5 returned to the liquid 14 to be nebulized for renebulization and the aerosol 26 is directed to the user. This is achieved with the assistance of the expansion compartment 94. Both the aerosol 26 and the spout 44 are directed to the expansion compartment 94 after moving along the curved surface 86. The curved surface 86 is effective in changing the direction of flow of the aerosol 26 and the non-nebulized part of the spout into the expansion 10 compartment 94 in an opposite direction relative to the general direction of travel of the liquid spout 44. The non-nebulized liquid under the action of gravity flows through the drainage pipe 96 returning back to the container 12 with the liquid 14 to be nebulized. The aerosol 26 behaves as a gas in passing out of the outlet pipe 88, which provides a lower energy route for exhausting the aerosol 26. 15 Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. For example, the specific shape and design of the nebulizer as well as the specific shape, design or configuration of components or assemblies that they comprise may vary provided they function as broadly defined. For example, the nebulizer may be asymmetric and not 20 include the tubular energy transmitter. All such variations and modifications are to be considered within the scope of the present invention the nature of which is to be determined from the foregoing description. It is to be understood that a reference herein to a prior art document does not constitute an admission that the document forms part of the common general knowledge 25 in the art in Australia or in any other country.

Claims

1. A nebulizer comprising: a container adapted to contain a liquid to be nebulized; a tubular energy transmitter having one end immersed in the liquid 5 proximate the container; and an energy source being operatively coupled to the container for nebulization of the liquid and being configured for transmission of energy to a focal region of the liquid which is forced toward an opposite end of the tubular energy transmitter. 10

2. A nebulizer as claimed in claim 1 wherein the energy source is positioned below the container.

3. A nebulizer as claimed in either of claims 1 or 2 wherein the tubular energy transmitter is positioned so that said one end is proximate the bottom of the container. 15

4. A nebulizer as claimed in any one of the preceding claims wherein the tubular energy transmitter vibrates at a frequency to form an aerosol proximate the opposite end of the energy transmitter.

5. A nebulizer as claimed in any one of the preceding claims wherein the nebulizer further comprises an aerosol tube positioned about at least a portion of the 20 tubular energy transmitter and having a cross-sectional area such that the positive pressure of the aerosol within the aerosol tube induces a pressure drop within the aerosol tube which propels the aerosol through the aerosol tube.

6. A nebulizer as claimed in either of claims 4 or 5 wherein an internal diameter of the aerosol tube is greater than an internal diameter of the tubular energy transmitter 25 at its opposite end.

7. A nebulizer as claimed in either of claims 6 or 7 wherein the aerosol tube is positioned so that it is substantially coaxial with the tubular energy transmitter. 9

8. A nebulizer as claimed in claim 7 wherein the aerosol tube is connected to the opposite end of the tubular energy transmitter.

9. A nebulizer as claimed in claim 8 wherein the energy source vibrates the liquid proximate the opposite end of the tubular energy transmitter. 5

10. A nebulizer as claimed in any one of claims 5 to 9 wherein the aerosol tube opens at its upper end into an expansion chamber which in turn communicates with an outlet duct.

11. A nebulizer as claimed in claim 10 wherein the expansion chamber is adapted to recirculate larger drops of the liquid back into the container. 10

12. A nebulizer as claimed in any one of the preceding claims wherein the energy source comprises an ultrasonic transducer for transmission of ultrasonic radiation energy.

13. A nebulizer is claimed in claim 12 wherein the ultrasonic transducer has a concave shaped surface. 15

14. A nebulizer as claimed in either of claims 12 or 13 wherein the ultrasonic transducer is arranged to transmit ultrasonic energy to a focal region of the liquid.

15. A nebulizer as claimed in claim 14 wherein the one end of the tubular energy transmitter is proximate the focal region.

16. A nebulizer as claimed in either of claims 14 or 15 wherein an internal diameter 20 of the tubular energy transmitter is substantially equal to a diameter of the focal region.

17. A nebulizer as claimed in any one of claims 12 to 16 wherein the tubular energy transmitter has a higher acoustic impedance than the liquid.

18. A nebulizer as claimed in claim 17 wherein the acoustic impedance of the 25 tubular energy transmitter is high enough to effect minimal acoustic energy loss during transmittal of the energy along the tubular energy transmitter. 10

19. A nebulizer as claimed in any one of the preceding claims being of an asymmetric configuration and excluding the tubular energy transmitter.

20. A nebulizer substantially as herein described with reference to and as illustrated in figures 2 to 4.