Aerosol generator having a multiple path heater arrangement and method of use thereof

Information

  • Patent Grant
  • 6681769
  • Patent Number
    6,681,769
  • Date Filed
    Thursday, December 6, 2001
    22 years ago
  • Date Issued
    Tuesday, January 27, 2004
    20 years ago
Abstract
An aerosol generator includes a heater arrangement having multiple heating sections and corresponding flow paths for volatilization of a fluid in liquid form. The flow paths can include first and second flow paths which are parallel to each other and sized such that the first flow path is smaller than the second flow path. During delivery of liquid to the flow paths, a smaller amount of vaporized liquid can be ejected from the first flow path, and the bulk of the vaporized liquid can be ejected from the second flow path.
Description




BACKGROUND OF THE INVENTION




1. Field of the Invention




The present invention relates generally to aerosol generators and, more particularly, to aerosol generators which include a heater for volatilizing liquid material. The present invention also relates to methods for generating an aerosol. The present invention has particular applicability to the generation of aerosols containing medicated material.




2. Description of the Related Art




Aerosols are gaseous suspensions of fine solid or liquid particles and are useful in a wide variety of applications. For example, medicated liquids and powders may be administered in aerosol form. Such medicated aerosols include, for example, materials which are useful in the treatment of respiratory ailments, in which case the aerosols may be inhaled into a patient's lungs. Aerosols may also be used in non-medicinal applications including, for example, dispensing air fresheners and insecticides and delivering paints and/or lubricants.




In aerosol inhalation applications, it is typically desirable to provide an aerosol having an average mass median particle diameter of less than 2 microns to facilitate deep lung penetration. Most known aerosol generators are incapable of generating aerosols having an average mass median particle diameter less than 2 microns. Also, in certain applications, it is generally desirable to deliver medicated material at high flow rates, for example, above 1 mg per second. Most known aerosol generators suited for delivering medicated material are incapable of delivering material at such high flow rates while maintaining a suitable average mass median particle diameter. In addition, most known aerosol generators deliver an imprecise amount of aerosol compared with the amount of aerosol that is intended to be delivered.




Commonly owned U.S. Pat. Nos. 5,743,251 and 6,234,167, disclose aerosol generators designed for volatilizing a liquid and ejecting the volatilized liquid into the atmosphere. The volatilized liquid subsequently condenses, thereby forming an aerosol. Such aerosol generators may utilize resistance heating materials to volatilize the liquid. However, generators having a single zone wherein the liquid is heated may not provide optimal delivery of the volatilized liquid.




In light of the foregoing, there exists a need in the art for the provision of an aerosol generator which provides improved aerosol delivery of volatilized liquid.




SUMMARY OF THE INVENTION




According to a first aspect of the present invention, an aerosol generator includes a liquid supply, a flow passage having at least one inlet that is in fluid communication with the liquid supply, the flow passage including at least first and second flow paths and at least one outlet, and a heater arrangement including first and second heating sections, the first heating section being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, and the second heating section being adapted to heat liquid in the second flow path sufficiently to vaporize liquid so as to form a vaporized liquid ejected from the at least one outlet.




The invention also provides a method for generating an aerosol using an aerosol generator comprising (1) a flow passage having an inlet in fluid communication with a liquid supply, the flow passage including at least first and second flow paths and at least one outlet; and (2) a multi-path heater arranged to volatilize fluid, wherein the heater includes at least first and second heating sections, the first heating section being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, and a second heating section being adapted to heat liquid in the second flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, the method comprising activating the heater arrangement of the aerosol generator to provide a differential heating rate in the first and second flow passages, and directing a smaller amount of volatilized fluid out of the first flow path, prior to directing the bulk of volatilized fluid out of the second flow path.











BRIEF DESCRIPTION OF THE DRAWINGS




The objects and advantages of the invention will become apparent from the following detailed description of the preferred embodiments thereof in connection with the accompanying drawings, in which:





FIG. 1

is a schematic view of an aerosol generator of an inhaler according to a first embodiment of the present invention;





FIG. 2

is a top plan view of a base plate of a multiple path heater arrangement according to the present invention;





FIG. 3

is a side sectional view along line A—A of a base plate according to the present invention; and





FIG. 4

is a top plan view of an assembled multiple path heater arrangement according to an embodiment of the present invention.





FIG. 5

is a top plan view of a base plate of a multiple path heater arrangement according to another preferred embodiment.











DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION




The present invention provides improvements in delivery of volatilized liquid from an aerosol generator via a multi-path heating arrangement which can deliver low volume mass per inhalation cycle, volatilize low solute containing solutions, minimize overheating, minimize power requirements, form volatilized liquid more quickly and/or form a predetermined amount of aerosol in a shorter time than in aerosol generators utilizing a single flow passage/heater arrangement. The invention is described with reference to embodiments shown in the drawing figures, wherein like reference numerals designate identical or corresponding elements throughout the several figures.




An aerosol generator


21


of an inhaler according to a first embodiment of the present invention is shown with reference to FIG.


1


. The aerosol generator


21


includes a liquid supply


33


which is in direct communication with a multiple path heater arrangement


23


. The heater arrangement


23


is connected to a power supply


29


, preferably a DC power source such as a battery. Liquid from liquid source


33


is delivered to flow paths


45


and


46


, by any suitable arrangement such as a syringe pump, pressurized container, valve arrangement or the like. In the embodiment shown, a valve


35


is used to deliver a predetermined amount of liquid to inlet


31


of a flow passage which branches into flow paths


45


,


46


. Activation of the valve can be controlled by a controller


48


upon receiving a signal from an optional puff activated sensor


37


. The controller also activates heater arrangement


23


by supplying power from power supply


29


whereby vaporized liquid is ejected from outlets


25


A,


25


B and/or aerosol is formed in optional mouth piece


39


for inhalation by a user of the device. If desired, a single outlet may be used in lieu of the two outlet arrangement.





FIGS. 2-4

show a multi-path heater arrangement according to a preferred embodiment of the invention wherein

FIG. 2

shows a top view of a base plate


24


,

FIG. 3

shows a side view of the base plate


24


, and

FIG. 4

shows a top view of a top plate


26


assembled to the base plate. The base plate


24


and top plate


26


when assembled form the multilayered composite heater arrangement


23


shown in FIG.


1


.




The aerosol generator


21


can produce an aerosol from a fluid in liquid form by volatilizing the fluid at a differential heating rate within the flow paths


45


and


46


. The flow paths


45


,


46


can have any desired configuration. For example, flow path


45


can comprise a straight and uniform cross-sectioned channel which is parallel to flow path


46


as shown in FIG.


1


. However, the flow paths could have non-uniform cross-sections, could be non-parallel and/or could be non-linear flow paths.





FIG. 2

shows an arrangement wherein the multiple path heater comprises at least two heating zones


40


,


41


. The first heating zone


40


is located along the first flow path


45


which preferably has a smaller cross-sectional area than the second flow path


46


. The smaller cross-sectional area of the first flow path


45


allows for faster heating of the fluid which passes through the heater arrangement


23


. As such, when the volatilized fluid enters through the liquid inlet hole


31


and flows through the first and second flow paths


45


and


46


, a preliminary amount of volatilized fluid will be produced within the smaller cross-sectional area defined by the first flow path


45


and delivered to outlet


25


A, prior to volatilization of fluid in the second flow path


46


. Thus, the aerosol generator can deliver an aerosol to a user of the device within a short time of actuation of the heater. While the preliminary amount of volatilized fluid is formed, the second heating section can heat sufficiently to deliver a bulk amount of volatilized fluid to outlet


25


B. The first heating zone


40


and second heating zone


41


can have the same or different thermal masses.




The flow paths


45


,


46


can be formed in a ceramic or polymer base plate


24


by molding, machining or other suitable technique. For example, the base plate


24


can be a green ceramic tape of alumina and the flow paths can be press formed into the ceramic tape. Alternatively, the base plate


24


can be a sintered ceramic plate and the flow paths


45


,


46


can be laser machined into the plate. The flow paths can have any desired configuration and/or dimensions in terms of length, width and depth. For example, the flow paths


45


,


46


can be parallel to each other with capillary dimensions, e.g., a depth of 0.01 to 10 mm, preferably 0.05 to 1 mm, and more preferably about 0.1 to 0.5 mm with the width and length of the flow path being any suitable dimensions, e.g., width of 1 mm or more and length of 10 mm or more. The width of flow path


46


is preferably 2 to 10 times greater than that of flow path


45


, e.g., flow path


46


can be around 4 times wider than flow path


45


. Alternatively, the smaller capillary passage can be defined by transverse cross sectional area of the passage which can be 8×10


−5


to 80 mm


2


, preferably 2×10


−3


to 8×10


−1


mm


2


and more preferably 8×10


−3


to 2×10


−1


mm


2


.




The power supply


29


is preferably battery operated by a controller and connected to the multiple path heater arrangement


23


via electrical feedthroughs


30


A and


30


B. This will allow for a continuous electrical circuit within the multiple path heater and faster heating of the heating zone


40


due to its smaller cross section. The heating zones


40


,


41


and optional intermediate section


42


can comprise a coating of resistance heating material located in flow paths


45


,


46


. For example, a resistance heating material such as platinum can be deposited such as by sputtering on surfaces of the base plate


24


defining the flow paths


45


,


46


. However, the heater can comprise a layer or layers of heating material on outer surfaces of top and/or bottom plates


24


,


26


. Liquid from a fluid supply can be supplied continuously or intermittently to inlet hole


31


. For inhaler devices, the inlet hole can have a size of 0.05 to 5 mm, preferably 0.1 to 1 mm. As the liquid enters into the fluid inlet hole


31


, the continuous electrical circuit allows for the heating of the heating zones


41


,


42


within fluid channel


43


as indicated in FIG.


3


. Heating zones


40


,


41


can be interconnected by intermediate zone


42


in the case where the heating zones


40


,


41


are formed from a continuous layer of resistance heating material. However, the heating zones


40


,


41


could be formed from discrete sections of heater material in which case separate electrical connections would be attached to each heater section.

FIG. 5

illustrates an embodiment of the aerosol generator including two power sources


29


, which power the first heating zone


40


independently of the second heating zone


41


.





FIG. 4

shows a top plate


26


assembled on the base plate


24


. The top and base plates can be held together with a suitable adhesive such as cement, epoxy, metallized glass, brazing material or the like. The heater arrangement


23


, which includes first and second heating sections


40


and


41


, is adapted to heat liquids in a first flow path


45


sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the first outlet


25


A. The second heating section


41


is adapted to heat liquid in the second flow path


46


sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the second outlet


25


B. For inhaler devices, the outlets


25


A and


25


B can be round holes having a diameter of 0.05 to 5 mm, preferably 0.1 to 1 mm. This arrangement allows for rapid heating of the liquid in the first flow path


45


.




While the invention has been described in detail with reference to preferred embodiments, it will be apparent to one skilled in the art that various changes can be made, and equivalents employed, without departing from the scope of the invention.



Claims
  • 1. An aerosol generator useful for generating vaporized fluid comprising:a liquid supply; a flow passage having at least one inlet in fluid communication with the liquid supply, the flow passage including at least first and second flow paths and at least one outlet; a heater arrangement including first and second heating sections, the first heating section being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, and the second heating section being adapted to heat liquid in the second flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet.
  • 2. The aerosol generator of claim 1, wherein the heater arrangement comprises at least one layer of resistance heating material and/or the at least first and second flow paths have capillary dimensions.
  • 3. The aerosol generator of claim 2, wherein the first and second heating sections have the same or different electrical resistance.
  • 4. The aerosol generator of claim 2, wherein the resistance heating material comprises a platinum coating.
  • 5. The aerosol generator of claim 2, wherein the heater arrangement includes an intermediate section of resistance heating material extending between the first and second heating sections.
  • 6. The aerosol generator of claim 2, wherein the first heating section is powered independently from the second heating section.
  • 7. The aerosol generator of claim 2, wherein the first and second heating sections are powered by a single electrical power source.
  • 8. The aerosol generator of claim 1, wherein the at least one outlet comprises first and second outlets.
  • 9. The aerosol generator of claim 1, further comprising a controller, valve and a sensor, the sensor detecting a delivery condition corresponding to delivery of a predetermined volume of aerosol, the controller being programmed to open the valve so as to deliver liquid to the first and second flow paths when the delivery condition is sensed by the sensor and to activate the heating sections to volatilize liquid in the first and second flow paths.
  • 10. The aerosol generator of claim 1, wherein the first heating section is thermally isolated from the second heating section.
  • 11. The aerosol generator of claim 1, wherein the first heating section is thermally integrated with the second heating section.
  • 12. The aerosol generator of claim 1, wherein the first and second heating sections have the same or different thermal masses.
  • 13. The aerosol generator of claim 1, further comprising a mouthpiece of an inhaler, the at least one outlet being located inside the mouthpiece so as to form an aerosol within the mouthpiece when volatilized liquid material is ejected from the at least one outlet.
  • 14. The aerosol generator of claim 1, wherein the first and second flow paths are in fluid connection at upstream ends thereof and the at least one inlet consists of a single inlet supplying liquid to the first and second flow paths.
  • 15. The aerosol generator of claim 1, wherein the first and second heating sections comprise planar strips of electrically resistive heating material.
  • 16. The aerosol generator of claim 1, wherein the first and second flow paths comprise first and second channels in a ceramic substrate.
  • 17. The aerosol generator of claim 16, wherein the first and second channels being less than or equal to 10 mm in depth.
  • 18. The aerosol generator of claim 16, wherein the first and second heating sections comprise resistance heating material in the channels.
  • 19. The aerosol generator of claim 18, wherein at least one electrical feedthrough extends through the ceramic substrate and supplies power to the heating sections.
  • 20. The aerosol generator of claim 19, wherein the at least one feedthrough comprises a first feedthrough connected to a downstream end of the first heating section and a second feedthrough connected to a downstream end of the second heating section.
  • 21. An aerosol generator useful for generating vaporized fluid, comprising:a base plate; a cover plate; a flow passage having at least one inlet adapted to receive liquid from a liquid supply, the flow passage including at least first and second flow paths between the base plate and the cover plate and including at least one outlet; a heater arrangement including first and second heating sections, the first heating section being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, and the second heating section being adapted to heat liquid in the second flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet.
  • 22. The aerosol generator of claim 21, wherein the first heating section comprises a layer of resistance heating material in the first channel and the second heating section comprises a layer of resistance heating material in the second channel.
  • 23. An aerosol generator useful for generating vaporized fluid, comprising:a flow passage having at least one inlet adapted to receive liquid from a liquid supply, the flow passage including at least first and second flow paths and at least one outlet; and a heater arrangement including first and second heating sections, the first and second heating sections comprising planar strips of electrically resistive heating material which are parallel to each other, the first heating section being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, and the second heating section being adapted to heat liquid in the second flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet.
  • 24. The aerosol generator of claim 23, wherein the first and second heating sections are interconnected by an intermediate section comprising a planar strip of electrically resistive heating material.
  • 25. A method for generating an aerosol, comprising:(a) supplying a material in liquid form to an inlet of an aerosol generator having a flow passage which includes first and second flow paths, the first flow path being smaller in size than the second flow path; and (b) heating the liquid in the first and second flow paths to a temperature sufficient to volatilize the liquid and eject volatilized liquid from at least one outlet, the heating being carried out by energizing first and second heating sections, the liquid in the first flow path being volatilized by the first heating section before the liquid in the second flow path is volatilized by the second heating section.
  • 26. The method of claim 25, wherein the aerosol generator includes a controller, a valve and a sensor, the method including:sensing a delivery condition with the sensor; sending a signal to the controller corresponding to detection of the delivery condition; opening the valve for delivery of a predetermined volume of liquid to the first and second flow paths when the controller receives the signal; supplying power to first and second heating sections which heat the liquid in the first and second flow paths; and closing the valve when the predetermined volume of fluid has been delivered to the first and second flow paths.
  • 27. An aerosol generator useful for generating vaporized fluid, comprising:a flow passage having at least one inlet adapted to receive liquid from a liquid supply, the flow passage including at least first and second flow paths and at least one outlet; and a heater arrangement including first and second heating sections, the first heating section being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, and the second heating section being adapted to heat liquid in the second flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet; wherein the first heating section volatilizes liquid in the first flow path faster than the second heating section volatilizes liquid in the second flow path when liquid is supplied to the first and second flow paths.
  • 28. An aerosol generator useful for generating vaporized fluid, comprising:a flow passage having at least one inlet adapted to receive liquid from a liquid supply, the flow passage including at least first and second flow paths and at least one outlet, the first flow path being sized to hold less than one-half an amount of liquid contained in the second flow path; and a heater arrangement including first and second heating sections, the first heating section being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, and the second heating section being adapted to heat liquid in the second flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet.
  • 29. An aerosol generator useful for generating vaporized fluid, comprising:a flow passage having at least one inlet adapted to receive liquid from a liquid supply, the flow passage including at least first and second flow paths and at least one outlet; and a heater arrangement including first and second heating sections, the first heating section being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, and the second heating section being adapted to heat liquid in the second flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, the first and second heating sections ejecting different volumes of vaporized liquid from the at least one outlet during delivery of a fixed volume of liquid to the flow passage.
  • 30. An aerosol generator useful for generating vaporized fluid, comprising:a flow passage having at least one inlet adapted to receive liquid from a liquid supply, the flow passage including at least first and second flow paths and at least one outlet; and a heater arrangement including first and second heating sections, the first heating section having a different cross-sectional area than the second heating section, the first heating section being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet, and the second heating section being adapted to heat liquid in the second flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet.
  • 31. A method for generating an aerosol, comprising steps of:(a) supplying a material in liquid form to an inlet of an aerosol generator having a flow passage which includes first and second flow paths; and (b) heating the liquid in the first and second flow paths to a temperature sufficient to volatilize the liquid and eject volatilized liquid from at least one outlet.
  • 32. A method for generating an aerosol, comprising:(a) supplying a material in liquid form to an inlet of an aerosol generator having a flow passage which includes first and second flow paths; and (b) heating the liquid in the first and second flow paths to a temperature sufficient to volatilize the liquid and eject a first amount of the volatilized liquid from a first outlet and eject a second amount of volatilized liquid from a second outlet, the first amount being smaller than the second amount.
  • 33. A heater arrangement useful for vaporizing liquid, comprising:a heater arrangement including first and second heating sections, the first heating section being disposed along a first flow path of a flow passage and being adapted to heat liquid in the first flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from at least one outlet of the flow passage, and the second heating section being disposed along a second flow path of the flow passage and adapted to heat liquid in the second flow path sufficiently to vaporize the liquid so as to form a vaporized liquid ejected from the at least one outlet; wherein the first heating section volatilizes liquid in the first flow path faster than the second heating section volatilizes liquid in the second flow path when liquid is supplied to the first and second flow paths.
US Referenced Citations (200)
Number Name Date Kind
2896856 Kravits Jul 1959 A
3084698 Smith Apr 1963 A
3157179 Paullus et al. Nov 1964 A
3162324 Houser Dec 1964 A
3431393 Katsuda Mar 1969 A
3486663 Humphrey Dec 1969 A
3658059 Steil Apr 1972 A
3716416 Adlhart et al. Feb 1973 A
3750961 Franz Aug 1973 A
3847304 Cohen Nov 1974 A
3859398 Havstad Jan 1975 A
3902635 Jinotti Sep 1975 A
3903883 Pecina et al. Sep 1975 A
3904083 Little Sep 1975 A
3967001 Almaula et al. Jun 1976 A
3987941 Blessing Oct 1976 A
3993246 Erb et al. Nov 1976 A
4042153 Callahan et al. Aug 1977 A
4060082 Lindberg et al. Nov 1977 A
4077542 Petterson Mar 1978 A
4161282 Erb et al. Jul 1979 A
4162501 Mitchell et al. Jul 1979 A
4215708 Bron Aug 1980 A
4231492 Rios Nov 1980 A
4258073 Payne Mar 1981 A
4261356 Turner et al. Apr 1981 A
4289003 Yang Sep 1981 A
4291838 Williams Sep 1981 A
4303083 Burruss, Jr. Dec 1981 A
4383171 Sinha et al. May 1983 A
4391308 Steiner Jul 1983 A
4395303 Weir Jul 1983 A
4433797 Galia Feb 1984 A
4471892 Coleman Sep 1984 A
4512341 Lester Apr 1985 A
4575609 Fassel et al. Mar 1986 A
4627432 Newell et al. Dec 1986 A
4649911 Knight et al. Mar 1987 A
4682010 Drapeau et al. Jul 1987 A
4695625 Macdonald Sep 1987 A
4700657 Butland Oct 1987 A
4730111 Vestal et al. Mar 1988 A
4735217 Gerth et al. Apr 1988 A
4744932 Browne May 1988 A
4749778 Fukuzawa et al. Jun 1988 A
4762995 Browner et al. Aug 1988 A
4776515 Michalchik Oct 1988 A
4790305 Zoltan et al. Dec 1988 A
4811731 Newell et al. Mar 1989 A
4819625 Howe Apr 1989 A
4819834 Thiel Apr 1989 A
4829996 Noakes et al. May 1989 A
4837260 Sato et al. Jun 1989 A
4848374 Chard et al. Jul 1989 A
4871115 Hessey Oct 1989 A
4871623 Hoopman et al. Oct 1989 A
4877989 Drews et al. Oct 1989 A
4911157 Miller Mar 1990 A
4922901 Brooks et al. May 1990 A
4926852 Zoltan et al. May 1990 A
4935624 Henion et al. Jun 1990 A
4941483 Ridings et al. Jul 1990 A
4947875 Brooks et al. Aug 1990 A
4974754 Wirz Dec 1990 A
4982097 Slivon et al. Jan 1991 A
4992206 Waldron Feb 1991 A
5021802 Allred Jun 1991 A
5044565 Alexander Sep 1991 A
5056511 Ronge Oct 1991 A
5060671 Counts et al. Oct 1991 A
5063921 Howe Nov 1991 A
5096092 Devine Mar 1992 A
5125441 Mette Jun 1992 A
5133343 Johnson, IV et al. Jul 1992 A
5134993 van der Linden et al. Aug 1992 A
5135009 Müller et al. Aug 1992 A
5144962 Counts et al. Sep 1992 A
5151827 Ven et al. Sep 1992 A
5178305 Keller Jan 1993 A
5184776 Minier Feb 1993 A
5217004 Blasnik et al. Jun 1993 A
5226441 Dunmire et al. Jul 1993 A
5228444 Burch Jul 1993 A
5230445 Rusnak Jul 1993 A
5231983 Matson et al. Aug 1993 A
5259370 Howe Nov 1993 A
5290540 Prince et al. Mar 1994 A
5298744 Mimura et al. Mar 1994 A
5299565 Brown Apr 1994 A
5322057 Raabe et al. Jun 1994 A
5327915 Porenski et al. Jul 1994 A
5342180 Daoud Aug 1994 A
5342645 Eisele et al. Aug 1994 A
5349946 McComb Sep 1994 A
5395445 Bohanan Mar 1995 A
5421489 Holzner, Sr. et al. Jun 1995 A
5462597 Jubran Oct 1995 A
5474059 Cooper Dec 1995 A
5515842 Ramseyer et al. May 1996 A
5522385 Lloyd et al. Jun 1996 A
5556964 Hofstraat et al. Sep 1996 A
5564442 MacDonald et al. Oct 1996 A
5565677 Wexler Oct 1996 A
5575929 Yu et al. Nov 1996 A
5585045 Heinonen et al. Dec 1996 A
5617844 King Apr 1997 A
5642728 Andersson et al. Jul 1997 A
5674860 Carling et al. Oct 1997 A
5682874 Grabenkort et al. Nov 1997 A
5730158 Collins et al. Mar 1998 A
5743251 Howell et al. Apr 1998 A
5756995 Maswadeh et al. May 1998 A
5765724 Amberg et al. Jun 1998 A
5823178 Lloyd et al. Oct 1998 A
5839430 Cama Nov 1998 A
5855202 Andrade Jan 1999 A
5856671 Henion et al. Jan 1999 A
5863652 Matsumura et al. Jan 1999 A
5869133 Anthony et al. Feb 1999 A
5872010 Karger et al. Feb 1999 A
5878752 Adams et al. Mar 1999 A
5881714 Yokoi et al. Mar 1999 A
5906202 Schuster et al. May 1999 A
5914122 Otterbeck et al. Jun 1999 A
5932249 Gruber et al. Aug 1999 A
5932315 Lum et al. Aug 1999 A
5934272 Lloyd et al. Aug 1999 A
5934273 Andersson et al. Aug 1999 A
5944025 Cook et al. Aug 1999 A
5951923 Horie et al. Sep 1999 A
5954979 Counts et al. Sep 1999 A
5957124 Lloyd et al. Sep 1999 A
5970973 Gonda et al. Oct 1999 A
5970974 Van Der Linden et al. Oct 1999 A
5978548 Holmstrand et al. Nov 1999 A
5993633 Smith et al. Nov 1999 A
6014970 Ivri et al. Jan 2000 A
6053176 Adams et al. Apr 2000 A
6054032 Haddad et al. Apr 2000 A
6069214 McCormick et al. May 2000 A
6069219 McCormick et al. May 2000 A
6070575 Gonda et al. Jun 2000 A
6071428 Franks et al. Jun 2000 A
6076522 Dwivedi et al. Jun 2000 A
6077543 Gordon et al. Jun 2000 A
6080721 Patton Jun 2000 A
6085740 Ivri et al. Jul 2000 A
6085753 Gonda et al. Jul 2000 A
6089228 Smith et al. Jul 2000 A
6095153 Kessler et al. Aug 2000 A
6098615 Lloyd et al. Aug 2000 A
6098620 Lloyd et al. Aug 2000 A
6103270 Johnson et al. Aug 2000 A
6116516 Gañán-Calvo Sep 2000 A
6116893 Peach Sep 2000 A
6119953 Gañán-Calvo et al. Sep 2000 A
6123068 Lloyd et al. Sep 2000 A
6123936 Platz et al. Sep 2000 A
6131567 Gonda et al. Oct 2000 A
6131570 Schuster et al. Oct 2000 A
6136346 Eljamal et al. Oct 2000 A
6138668 Patton et al. Oct 2000 A
6155268 Takeuchi Dec 2000 A
6158431 Poole Dec 2000 A
6158676 Hughes Dec 2000 A
6159188 Laibovitz et al. Dec 2000 A
6164630 Birdsell et al. Dec 2000 A
6165463 Platz et al. Dec 2000 A
6167880 Gonda et al. Jan 2001 B1
6174469 Gañán-Calvo Jan 2001 B1
6182712 Stout et al. Feb 2001 B1
6187214 Gañán-Calvo Feb 2001 B1
6187344 Eljamal et al. Feb 2001 B1
6189803 Gañán-Calvo Feb 2001 B1
6192882 Gonda Feb 2001 B1
6197835 Gañán-Calvo Mar 2001 B1
6205999 Ivri et al. Mar 2001 B1
6206242 Amberg et al. Mar 2001 B1
6207135 Rössling et al. Mar 2001 B1
6223746 Jewett et al. May 2001 B1
6230706 Gonda et al. May 2001 B1
6231851 Platz et al. May 2001 B1
6234167 Cox et al. May 2001 B1
6234402 Gañán-Calvo May 2001 B1
6235177 Borland et al. May 2001 B1
6250298 Gonda et al. Jun 2001 B1
6257233 Burr et al. Jul 2001 B1
6258341 Foster et al. Jul 2001 B1
6263872 Schuster et al. Jul 2001 B1
6267155 Parks et al. Jul 2001 B1
6275650 Lambert Aug 2001 B1
6276347 Hunt Aug 2001 B1
6284525 Mathies et al. Sep 2001 B1
6288360 Beste Sep 2001 B1
6290685 Insley et al. Sep 2001 B1
6294204 Rössling et al. Sep 2001 B1
6295986 Patel et al. Oct 2001 B1
6318361 Sosiak Nov 2001 B1
6390453 Frederickson et al. May 2002 B1
20010032647 Schuster et al. Oct 2001 A1
Foreign Referenced Citations (13)
Number Date Country
354004 Sep 1928 BE
354094 Sep 1928 BE
1036470 Aug 1958 DE
0358114 Mar 1990 EP
0642802 May 1996 EP
667979 Oct 1929 FR
168128 Nov 1977 HU
216121 Mar 1991 HU
207457 Apr 1993 HU
P953409 Jun 1994 HU
9409842 May 1994 WO
9817131 Apr 1998 WO
0021598 Apr 2000 WO
Non-Patent Literature Citations (10)
Entry
Notification of Transmittal of the International Search Report or the Declaration for PCT/US02/38681 dated Apr. 1, 2003.
Barry, P.W. et al. “In Vitro Comparison of the Amount of Salbutamol Available for Inhalation From Different Formulations Used with Different Spacer Devices” Eur Respir J 1997; 10: 1345-1348.
Byron, Peter R. Ph.D., Chairman, “Recommendations of the USP Advisory Panel on Aerosols on the USP General Chapters on Aerosols (601) and Uniformity of Dosage Units (905)”, Pharmacopeial Forum, vol. 20, No. 3, pp. 7477-7505, May-Jun. 1994 (023).
Hindle, Michael et al., “High Efficiency Aerosol Production Using the Capillary Aerosol Generator” PharmSci 1998; 1: (1: suppl) S211.
Hindle, Michael et al., “High Efficiency Fine Particle Generation Using Novel Condensation Technology”, Respiratory Drug Delivery VI (eds Dalby, R.N., Byron, P.R. & Farr, S.J.) Interpharm Press, Buffalo Grove, IL 1998 pp. 97-102.
Hou, Shuguang et al. Solution Stability of Budensonide in Novel Aerosol Formulations Abstract No. 2582, Solid State Physical Pharmacy, Nov. 17, 1998, p. S-307.
Kousaka, Yasuo et al., “Generation of Aerosol Particles by Boiling of Suspensions”, Aerosol Science and Technology, 21:236-240 (1994) (023).
Morén, Folke “Drug Deposition of Pressurized Inhalation Aerosols I. Influence of Actuator Tube Design” AB Draco (Subsidiary of AB Astra, Sweden) Research and Development Laboratories Pack, S-221 01 Lund (Sweden), International Journal of Pharmaceutrics, 1 (1978) 205-212.
Newman, Stephen P. et al. “Deposition of Pressurized Suspension Aerosols Inhaled Through Extension Devices1-3” Am Rev Respir Dis 1981; 124:317-320.
Roth, G. et al. High Performance Liquid Chromatographic Determination of Epimers, Impurities, and Content of the Glucocorticoid Budesonide and Preparation of Primary Standard, Journal of Pharmaceutical Sciences, vol. 69, No. 7, pp. 766-770, Jul. 1980.