Vapor driven aerosol generator and method of use thereof

Information

  • Patent Grant
  • 6491233
  • Patent Number
    6,491,233
  • Date Filed
    Friday, December 22, 2000
    24 years ago
  • Date Issued
    Tuesday, December 10, 2002
    22 years ago
Abstract
An aerosol generator includes a fluid supply which supplies fluid to a fluid passage, a main heater which heats the fluid into a gaseous state and a preheater which delivers a volume of fluid to the main heater. The preheater can be located in or adjacent a metering chamber which receives a predetermined volume of fluid, the preheater heating a portion of the fluid so as to form a vapor bubble which ejects the remaining fluid from the chamber. An outlet of the aerosol generator is arranged to receive the volatilized fluid formed by the main heater and direct the volatilized fluid out of the fluid passage. The aerosol generator can be used to generate aerosols containing medicated materials.
Description




BACKGROUND OF THE INVENTION




1. Field of the Invention




The present invention relates generally to aerosol generators and, more particularly, to vapor driven aerosol generators. The aerosol generators of the invention are able to generate aerosols without requiring the use of compressed gas propellants. 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.




The related art discloses aerosol generators which employ various techniques for delivering an aerosol. A particularly useful technique involves volatilizing a fluid and ejecting the volatilized fluid into the atmosphere. The volatilized fluid subsequently condenses, thereby forming an aerosol. See, for example, commonly assigned U.S. Pat. No. 5,743,251, the entire contents of which document are hereby incorporated by reference. Such aerosol generators may eliminate or conspicuously reduce some or all of the aforementioned problems associated with the known aerosol generators. However, since these aerosol generators employ heat-generating systems, heat resistive material and, in some cases, various control devices, pumps and valves, the manufacture and assembly of such aerosol generators can be complicated and expensive.




In light of the foregoing, there exists a need in the art for the provision of an aerosol generator which overcomes or conspicuously ameliorates the above described shortcomings in the related art. Accordingly, it is an object of the present invention to provide a vapor driven aerosol generator which produces an aerosol from a fluid by volatilizing the fluid and directing the volatilized fluid therefrom.




Other objects and aspects of the present invention will become apparent to one of ordinary skill in the art upon review of the specification, drawings and claims appended hereto.




SUMMARY OF THE INVENTION




The invention provides an aerosol generator which includes a fluid passage having an upstream and a downstream end, a heater arranged to heat fluid in the passage into a gaseous state, a fluid supply arranged to provide a fluid to the upstream end of the passage, a preheater located between the fluid supply and the main heater, the preheater including a heating element which heats a portion of the fluid in the passage into a gaseous state such that fluid in the passage downstream of the heating element is driven through the passage in a downstream direction.




The heating element is preferably located in a chamber having a predetermined volume and/or the fluid supply includes a valve which closes the passage when the heating element heats the fluid into a gaseous state. If desired, the heating element can be located along an inner wall of a metering chamber, the metering chamber being sized to receive a predetermined volume of fluid to be emitted as an aerosol from the aerosol generator. The passage can be located in an organic or inorganic material selected from one or more polymer, metal and ceramic materials. For instance, the passage can be located in a ceramic laminate wherein the passage is defined by a recess in a surface of a first ceramic layer and a surface of a second ceramic layer bonded to the first ceramic layer. The heating element can comprise a layer of resistance heating material located along one or more walls of the passage.











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 diagram of an exemplary aerosol generator in accordance with the invention;





FIG. 2

is a cross section of an exemplary aerosol generator in accordance with the invention; and





FIG. 3

is a cross section of another exemplary aerosol generator in accordance with the invention.











DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION




When referring to the drawing figures, like reference numerals designate identical or corresponding elements throughout the several figures.





FIG. 1

shows a vapor driven aerosol generator


10


in accordance with one embodiment of the invention. As shown, the aerosol generator


10


includes a source


12


of fluid, a valve


14


, a chamber


16


, a valve


18


, a passage


20


, a mouthpiece


22


, an optional sensor


24


and a controller


26


. In addition, the aerosol generator


10


includes a preheater


28


and a main heater


30


. The controller


26


includes suitable electrical connections and ancillary equipment such as a battery which cooperates with the controller for operating the valves


14


,


18


, the sensor


24


and the heaters


28


,


30


. In operation, the valve


14


can be opened to allow a desired volume of fluid from the source


12


to enter the chamber


16


during which time the valve


18


can be closed to prevent the incoming fluid from advancing into the passage


20


. Filling of the chamber


16


can occur prior to or subsequent to detection by the sensor


24


of vacuum pressure applied to the mouthpiece


22


by a user attempting to inhale aerosol from the inhaler


10


. Once the chamber


16


contains a predetermined volume of fluid, the controller


26


closes valve


14


and opens valve


18


while operating the preheater


28


to drive the fluid into the passage


20


. While the fluid passes through the passage


20


, the controller


26


operates the main heater


30


to heat the fluid to a suitable temperature for volatilizing the fluid therein. The volatilized fluid exits an outlet


32


of the passage


20


and the volatilized fluid forms an aerosol which can be inhaled by a user drawing upon the mouthpiece


22


.




The aerosol generator shown in

FIG. 1

can be modified to utilize different fluid supply arrangements. For instance, the fluid source can comprise a delivery valve which delivers a predetermined volume of fluid to the chamber


16


in which case the chamber


16


need not be sized to hold a precise volume of liquid. Alternatively, the chamber can be sized to hold a predetermined volume of fluid and the fluid supply can comprise a pressurized source of fluid which fills the chamber when valve


14


is opened. The preheater


28


heats the fluid in the chamber


16


such that a vapor bubble is formed which expands and drives the remaining liquid from the chamber


16


into the passage


20


. If desired, valves


14


,


18


could be omitted and the fluid source


12


can include a delivery arrangement which supplies a predetermined volume of fluid to the chamber


16


. Further, the main heater


30


can be an individual heater or a plurality of heaters arranged to volatilize the liquid in passage


20


. In the case of manual operations, the sensor


24


can be omitted such as in the case where the aerosol generator


10


is operated manually by a mechanical switch, electrical switch or other suitable technique.





FIG. 2

shows a top cutaway view of a vapor driven aerosol generator


40


in accordance with another embodiment of the invention. As shown, the aerosol generator


40


includes a fluid supply


42


, a chamber


44


, a passage


46


, a preheater


48


and a main heater


50


. The preheater


48


can be arranged on one side of the chamber


44


such that fluid in the chamber


44


is heated to form a vapor bubble which expands and drives the remaining fluid in the chamber


44


into the passage


46


. If desired, an additional preheater


52


can be provided in the chamber


44


in order to provide additional heating of the fluid. The heaters


48


,


52


extend horizontally along bottom and top walls of the chamber


44


. The heaters


48


,


50


,


52


are preferably thin films of resistance heating material. In order to pass electrical current through the heaters, the heaters can be in electrical contact with suitable electrical contacts


54


. A suitable power source such as a battery can be used to deliver sufficient direct current to the contacts


54


in order to heat the heaters


48


,


50


,


52


to desired temperatures. Further, operation of the heaters and supply of fluid from the fluid source


42


can be controlled by a suitable controller as in the case of the first embodiment.




Like the embodiment shown in

FIG. 1

, the embodiment shown in

FIG. 2

can be modified to incorporate different fluid supply arrangements and/or heating arrangements. However, it is preferred that the chamber


44


include at least one preheater therein or associated therewith such that fluid in the chamber


44


can be heated to form a vapor bubble which drives the fluid in the chamber


44


into the passage


46


.





FIG. 3

shows a side view of a third embodiment of a vapor driven aerosol generator in accordance with the invention. As shown, the aerosol generator


60


includes a fluid supply


62


, a chamber


64


, a passage


66


, a preheater


68


and a main heater


70


. The aerosol generator


60


can be formed from solid state components such as layers


72


,


74


,


76


of metal, organic or ceramic material such as a polymer material or ceramic material. If desired, layers


74


and


76


can comprise a single layer which has been machined or etched to form the passage


66


and the chamber


64


. Alternatively, one or more layers can be interposed between the layers


74


and


76


so as to form the passage


66


and the chamber


64


. As in the case of the embodiment shown in

FIG. 2

, the heaters


68


,


70


can be supplied power by contacts


78


. The heater


68


is arranged to extend vertically along an inner sidewall of the chamber


64


. In arrangements wherein the heater contacts the fluid, it is desirable to coat the heater with a material which is nonreactive with the fluid, e.g., glass or metal such as stainless steel.




The fluid may include any material capable of volatilization by the aerosol generator. In a preferred embodiment, the fluid does not decompose when exposed to the heat required for volatilization thereof. The fluid preferably includes a medicated material such as, for example, a material that is useful in the treatment of respiratory ailments. In such applications, the generated aerosol may be inhaled into a user's lungs. Alternatively, the fluid may include a non-medicated material.




In the foregoing embodiments, the fluid passage can be defined by a capillary tube or a channel in a multi-layered arrangement wherein the layers are formed from a heat-resistant material that is preferably capable of withstanding the temperatures and pressures generated in the fluid passage. The heat-resistant material is more preferably capable of withstanding repeated heating cycles. Also, the heat-resistant material preferably does not react with the fluid contained in the fluid passage. The heat-resistant material may include, for example, alumina, zirconia, silica, aluminum silicate, titania, yttria-stabilized zirconia or mixtures thereof, preferably alumina. The layers may be of any size suitable for aerosol generation. According to a preferred embodiment, each layer can have a length of from about 1 to 100 mm, more preferably about 15 mm; a width of from about 1 to 100 mm, more preferably about 15 mm; and a thickness of from about 0.001 to 10 mm, more preferably about 0.076 mm.




The layers can be configured to at least partially define the fluid passage. In an exemplary embodiment of the present invention, a channel is in a layer or the channel can be defined by adding one or more layers of material between first and second layers. The layers can be attached together, thereby enclosing the channel therebetween. In this manner, the channel defines the fluid passage.




The layers may be attached together using various techniques, including, for example, adhesive bonding. The adhesive material used to attach the layers is preferably capable of withstanding repeated heating cycles and may include, for example, a metal, a cement, an epoxy, an acrylic, a cyanoacrylic or mixtures thereof, preferably an acrylic cement. Alternatively, other techniques may be used to attach the layers together such as, for example, mechanical or metallurgical bonding such as a brazing material.




The fluid passage is preferably linear to facilitate the flow of the fluid therethrough. Alternatively, the fluid passage can be non-linear in two or three dimensions such as in the case where the direction of fluid flow through the passage contains at least one turn. An outlet at the downstream end of the fluid passage can be sized to achieve a desired aerosol particle size distribution. In a preferred embodiment, the outlet is circular and has a diameter of about from 0.01 to 5 mm, more preferably about 0.1 mm.




The outlet may be disposed at an angle, for example, 10 to 160°, with respect to the axis of fluid flow within the fluid passage, to direct the flow of the volatilized fluid out of the fluid passage in a desired direction. According to an alternative embodiment, the fluid passage can extend through a side wall of the layers, and the outlet can be defined by the furthest downstream portion of the fluid passage. A conduit (not shown) may be connected to receive the volatilized fluid from the outlet to further direct the flow of volatilized fluid in a desired direction. Such a conduit can have a diameter of from about 0.01 to 5 mm.




In a preferred embodiment, a valve and/or a pump can be used to control the flow of fluid from the fluid supply to the fluid passage. The valve and/or the pump may be manually operated or a controller may manipulate the valve and/or the pump based on various parameters including, for example, the amount of time the valve remains in the open position, or the volumetric amount of fluid that is supplied to the fluid passage. In this manner, the valve and/or the pump may enable the liquid supply to deliver a predetermined volume of fluid in liquid phase to the fluid passage. In an alternative embodiment, the fluid in liquid phase can be contained in a chamber, and the fluid can be delivered by compressing the fluid in the chamber using a piston.




The fluid supply provides the fluid to be volatilized in fluid phase to the fluid passage. The fluid in liquid phase may be stored in the liquid supply at a pressure above atmospheric to facilitate delivery of the fluid to the fluid passage. In an exemplary embodiment, the fluid supply comprises a refillable storage chamber formed of a material suitable for containing the fluid to be volatilized. Alternatively, the fluid supply comprises a disposable storage chamber which, upon exhaustion of the fluid, is discarded and replaced by a new storage chamber.




The fluid passage may contain any amount of fluid in liquid phase which is capable of being volatilized by the heater of the aerosol generator. For example, the fluid passage may have a liquid volumetric capacity of from about 1×10


−6


ml to 0.005 ml. Alternatively, the fluid passage may have a liquid volumetric capacity of greater than about 0.005 ml, preferably from about 0.1 ml to 1.0 In aerosol inhalation applications, the fluid passage may have a liquid volumetric capacity which is sufficient for containing a predetermined amount of fluid that comprises a metered quantity of fluid.




The main heater for heating the fluid passage and the preheater for heating the chamber preferably include a film forming an electrically resistive heating material which is different from the heat-resistant material used to form the layers of the aerosol generator. For example, the resistive material may include a pure metal, metal alloy or metal compound such as platinum, titanium nitride, stainless steel, nickel chromium or mixtures thereof. Additional resistive materials include composite layers such as self-regulating heater materials. The main heater may be sized to be capable of generating a sufficient amount of heat to vaporize the fluid present in the fluid passage. In a preferred embodiment, the main heater has a length of from about 1 to 100 mm, more preferably about 10 mm; a width of from about 0.1 to 10 mm, more preferably about 0.5 mm; a thickness of from about 1 to 10 microns, more preferably about 3 microns; and an electrical resistance of from about 0.1 to 10 ohms, more preferably about 0.65 ohm.




Using a material for forming the heaters which is different from the material used to form the layers allows the resistance through the heaters to be easily adjusted by varying various parameters including, for example, the dimensions and amount of heat produced by the heaters may be adjusted for various applications. the material of the heaters. In this manner, the resistance of the heaters and the




The resistive material of the heaters may be attached to the layers using various techniques. For example, the resistive material may be sputtered, printed, bonded or coated upon the layers. Deposition by sputtering includes, for example, DC magnetron sputter deposition. Deposition by bonding includes, for example, eutectically bonding the resistive material using sputtered material including, for example, copper or copper sheet material. Alternatively, vacuum evaporation, chemical deposition, electroplating and chemical vapor deposition may be used to deposit the resistive material.




Various factors contribute to the stability of the bond between the heater and the layers. For example, to enhance bonding, the arithmetic average of the surface roughness of the surface upon which the resistive material is disposed preferably is greater than or equal to about 1 microinch, more preferably from about 1 to 100 microinches, and most preferably from about 12 to 22 microinches. In addition, the heat-resistant material of the layers and the resistive material of the heater preferably have comparable coefficients of thermal expansion to minimize or prevent thermally induced delamination.




In a preferred embodiment, the heater is in electrical contact with first and second contacts which pass an electrical current through the heater. In this embodiment, the power supply which provides the electrical current to the heater is in electrical contact with the first and second contacts.




The first and second contacts of the heater are preferably formed from a material which has a lower resistance than that of the resistive material of the heater. For example, the first and second contacts typically include copper or a copper alloy such as, for example, phosphor bronze and Si bronze, and preferably copper or a copper alloy comprising at least 80% copper. Use of such materials prevents or reduces the heating of the contacts prior to the heating of the heater. The contacts are sized to be capable of passing an electrical current through the heater. The contacts may be attached to the layers and/or heater using any of the techniques used to attach the resistive material to the layers, as discussed above.




In each of the above embodiments, a single heater or multiple heaters may be used for the main heater or preheater. The use of multiple heaters for the main heater in the aerosol generator may enable a more uniform distribution of heat within the fluid passage. Alternatively, the use of multiple heaters may enable different zones of the fluid passage to be maintained at different temperatures. Such differing temperature zones in the fluid passage may be useful in fluid temperature control devices, as discussed in U.S. application Ser No. 09/742,322, filed Dec. 22, 2000, the entire contents of which document are incorporated by reference herein.




The aerosol generator may generate an aerosol either on an intermittent or continuous basis. For intermittent generation of an aerosol, for example, the liquid supply provides the fluid in liquid phase to the fluid passage each time the generation of an aerosol is desired. The valve and/or the pump may be used to actuate the flow of fluid from the liquid supply to the fluid passage. The remaining fluid in liquid phase between the liquid supply and the fluid passage is prevented from traveling back into the liquid supply by any suitable device such as the valve and/or the pump to prevent expansion of the volatilized fluid in the direction opposite the outlet.




For generating an intermittent aerosol in inhalation applications, the aerosol generator is preferably provided with a puff-actuated sensor, which is preferably arranged inside a mouthpiece disposed proximate to the outlet. The puff-actuated sensor can be used to actuate the valve and/or the pump and the heaters so that the liquid supply provides the fluid in liquid phase to the chamber, the preheater drives the fluid into the fluid passage, and the fluid is volatilized by the main heater. The puff-actuated sensor is preferably sensitive to pressure drops occurring in the mouthpiece when a user draws on the mouthpiece. The aerosol generator is preferably provided with circuitry such that, when a user draws on the mouthpiece, the valve and/or pump supply fluid in liquid phase to the fluid passage and the heaters are heated by the power supply.




A puff-actuated sensor suitable for use in the aerosol generator includes, for example, Model 163PC01D35 silicon sensor, manufactured by the MicroSwitch division of Honeywell, Inc., located in Freeport, Ill., or SLP004D 0-4” H


2


O Basic Sensor Element, manufactured by SenSym, Inc., located in Milpitas, Calif. Other known flow-sensing devices, such as those using hot-wire anemometry principles, may also be suitable for use with the aerosol generator. While the invention has been described in detail with reference to preferred embodiments thereof, 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, comprising:a fluid passage having an upstream and a downstream end; a main heater arranged to heat liquid in the fluid passage into a gaseous state; a fluid supply arranged to provide a fluid to the upstream end of the fluid passage; and a preheater located between the fluid supply and the main heater, the preheater including a heating element which heats a portion of fluid into a gaseous state such that fluid in the fluid passage downstream of the heating element is driven through the fluid passage in a downstream direction.
  • 2. The aerosol generator of claim 1, wherein the heating element is located in a chamber having a volume larger than the portion of the fluid heated into a gaseous state by the preheater.
  • 3. The aerosol generator of claim 1, wherein the fluid supply includes a valve which closes the fluid passage when the heating element heats the portion of the fluid into a gaseous state.
  • 4. The aerosol generator of claim 1, wherein the heating element is located along an inner wall of a metering chamber, the metering chamber being sized to receive a predetermined volume of fluid to be emitted as an aerosol from the aerosol generator.
  • 5. The aerosol generator of claim 1, wherein the fluid passage is located in an organic or inorganic material selected from one or more polymer, metal and ceramic materials.
  • 6. The aerosol generator of claim 1, wherein the fluid passage is located in a ceramic laminate, the fluid passage being defined by a recess in a surface of at least one ceramic layer.
  • 7. The aerosol generator of claim 6, wherein the ceramic laminate includes layers of a material selected from the group consisting of alumina, zirconia, silica and mixtures thereof.
  • 8. The aerosol generator of claim 1, wherein the heating element comprises a layer of resistance heating material located along one or more walls of the fluid passage.
  • 9. The aerosol generator of claim 1, wherein the preheater is arranged to directly contact the fluid in the fluid passage.
  • 10. The aerosol generator of claim 1, wherein the preheater is arranged to conduct heat through an intermediate layer of material to the fluid in the fluid passage.
  • 11. The aerosol generator of claim 1, wherein the preheater comprises a material selected from the group consisting of platinum, titanium nitride, stainless steel, nickel chromium and mixtures thereof.
  • 12. The aerosol generator of claim 1, wherein the preheater is sputtered, printed, adhesively bonded or coated on a layer of electrically insulating material.
  • 13. The aerosol generator of claim 1, wherein the fluid passage extends in a linear or nonlinear direction.
  • 14. The aerosol generator of claim 1, wherein the preheater is in electrical contact with first and second contacts which pass an electrical current through the preheater.
  • 15. The aerosol generator of claim 1, wherein the fluid comprises a medicated material.
  • 16. The aerosol generator of claim 1, further comprising a power supply for heating the preheater.
  • 17. A method for generating an aerosol, comprising the steps of:(a) supplying fluid to a fluid passage wherein a first portion of the fluid passage is heated by a preheater and a second portion of the fluid passage is heated by a main heater which volatilizes the fluid; (b) heating the preheater so as to volatilize a portion of the fluid in the fluid passage so as to form a vapor bubble which conveys non-volatilized fluid to the second portion of the fluid passage; (c) heating the main heater so as to volatilize the fluid in the second portion of the fluid passage; and (d) forming an aerosol by ejecting the volatilized fluid out of an outlet of the fluid passage.
  • 18. The method of claim 17, wherein the preheater heats the fluid in the fluid passage by thermal conduction.
  • 19. The method of claim 17, wherein the preheater heats the fluid by thermal conduction through an intermediate layer of material.
  • 20. The method of claim 17, wherein the fluid passage comprises a channel disposed in a multilayer arrangement and the volatilized fluid is ejected through an opening in a surface of the multilayer arrangement.
  • 21. A method of making an aerosol generator, comprising:forming a fluid passage having an upstream and a downstream end; forming a main heater arranged to heat liquid in the fluid passage into a gaseous state; forming a fluid supply arranged to provide a fluid to the upstream end of the fluid passage; and forming a preheater located between the fluid supply and the main heater, the preheater including a heating element which heats a portion of fluid into a gaseous state such that fluid in the fluid passage downstream of the heating element is driven through the fluid passage in a downstream direction.
US Referenced Citations (204)
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
3995371 O'Keefe Dec 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
4259409 Arnold 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
5509557 Jimarez et al. Apr 1996 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
5894841 Voges Apr 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
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
6071554 Isomura 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. Jun 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
6151827 Smith et al. Nov 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
20010032647 Schuster et al. Oct 2001 A1
Foreign Referenced Citations (12)
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
Non-Patent Literature Citations (12)
Entry
Notification of Transmittal of the International Search Report or the Declaration dated Apr. 24, 2002 for PCT/US01/44810.
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.
Copending Application No. 09/742,322 naming Kenneth A. Cox, Walter Allen Nichols, F. Murphy Sprinkel, Jr., Douglas D. Mcrae and William R. Sweeney as inventor(s) and filed on Dec. 22, 2000.
Notification of Transmittal of International Preliminary Examination Report for PCT/US01/44810 dated Sep. 10, 2002.