Aerosol generator having inductive heater and method of use thereof

Information

  • Patent Grant
  • 6681998
  • Patent Number
    6,681,998
  • Date Filed
    Friday, December 22, 2000
    24 years ago
  • Date Issued
    Tuesday, January 27, 2004
    20 years ago
Abstract
An aerosol generator includes an induction heating arrangement to vaporize fluid contained in a fluid passage. The vapor is then expelled from the fluid passage into the air creating a mist that forms the aerosol. The aerosol generator includes an excitation coil that inductively heats a heating element which transfers heat to the fluid in the fluid passage. The fluid passage can be located in a metal tube which can be removably mounted in the aerosol generator.
Description




FIELD OF THE INVENTION




The present invention relates to aerosol generators and methods for generating an aerosol. In particular, the aerosol generators are vapor driven, thus are able to generate aerosols without requiring the use of compressed gas propellants. The present invention has particular applicability to the generation of aerosols containing medicated material.




DESCRIPTION OF RELATED ART




Aerosols are useful in a wide variety of applications. For example, it is often desirable to treat respiratory ailments with, or deliver drugs by means of, aerosol sprays of finely divided particles of liquid and/or solid, e.g., powder, medicaments, etc., which are inhaled into a patient's lungs. Aerosols are also used for purposes such as providing desired scents to rooms distributing insecticide and delivering paint and lubricant.




Various techniques are known for generating aerosols. For example, U.S. Pat. Nos. 4,811,731 and 4,627,432 disclose devices for administering medicaments to patients in which a capsule is pierced by a pin to release a medicament in powder form. A user then inhales the released medicament through an opening in the device. While such devices may be acceptable for use in delivering medicaments in powder form, they are not suited to delivering medicaments in liquid form. The devices are also, of course, not well-suited to delivery of medicaments to persons who might have difficulty in generating a sufficient flow of air through the device to properly inhale the medicaments, such as asthma sufferers. The devices are also not suited for delivery of materials in applications other than medicament delivery.




Another well-known technique for generating an aerosol involves the use of a manually operated pump which draws liquid from a reservoir and forces it through a small nozzle opening to form a fine spray. A disadvantage of such aerosol generators, at least in medicament delivery applications, is the difficulty of properly synchronizing inhalation with pumping. More importantly, however, because such aerosol generators tend to produce particles of large size, their use as inhalers is compromised because large particles tend to not penetrate deep into the lungs.




One of the more popular techniques for generating an aerosol including liquid or powder particles involves the use of a compressed propellant, often containing a chlorofluoro-carbon (CFC) or methylchloroform, to entrain a material, usually by the Venturi principle. For example, inhalers containing compressed propellants such as compressed gas for entraining a medicament are often operated by depressing a button to release a short charge of the compressed propellant. The propellant entrains the medicament as the propellant flows over a reservoir of the medicament so that the propellant and the medicament can be inhaled by the user.




In propellant-based arrangements, a medicament may not be properly delivered to the patient's lungs when it is necessary for the user to time the depression of an actuator such as a button with inhalation. Moreover, aerosols generated by propellant-based arrangements may have particles that are too large to insure efficient and consistent deep lung penetration. Although propellant-based aerosol generators have wide application for uses such as antiperspirant and deodorant sprays and spray paint, their use is often limited because of the well-known adverse environmental effects of CFC's and methylchloroform, which are among the most popular propellants used in aerosol generators of this type.




In drug delivery applications, it is typically desirable to provide an aerosol having average mass median particle diameters of less than 2 microns to facilitate deep lung penetration. Most known aerosol generators are incapable of generating aerosols having average mass median particle diameters less than 2 microns. It is also desirable, in certain drug delivery applications, to deliver medicaments at high flow rates, e.g., above 1 milligram per second. Most known aerosol generators suited for drug delivery are incapable of delivering such high flow rates in the 0.2 to 2.0 micron size range.




U.S. Pat. No. 5,743,251, which is hereby incorporated by reference in its entirety, discloses an aerosol generator, along with certain principles of operation and materials used in an aerosol generator, as well as a method of producing an aerosol. The aerosol generator disclosed according to the '251 patent is a significant improvement over earlier aerosol generators, such as those used as inhaler devices.




SUMMARY OF THE INVENTION




The invention provides methods and apparatus for producing an aerosol by using inductive heating. The inductive heater heats fluid in a fluid passage so as to produce a vapor which forms an aerosol when it is exposed to the air outside the fluid passage.




The inductive heater can include one or more coils that produce an electromagnetic field when an electrical current is passed therethrough. The flux from this electromagnetic field produces eddy currents in a heating element to thereby heat the heating element and transfer heat to the fluid by use of the inductive heater.




The inductive heater can be fabricated using various materials. Preferably, the heating element has electrically conductive material associated with it. For example, the heating element can be made of metal or it can be made of glass and have a metal coating on it. A flux concentrator can optionally be used to increase the flux concentration in the heating element and thereby heat the fluid passage at a faster rate.




In a preferred embodiment, the fluid passage can be in a capillary tube that is replaceable. For example, the tube can be mounted in the aerosol generator such that it can be pulled out and replaced with a new one. In another embodiment, the fluid passage can be a channel in a multilayered composite.











BRIEF DESCRIPTION OF THE DRAWINGS




Various exemplary embodiments of this invention will be described in detail, with reference to the following figures, wherein:





FIG. 1

is an exemplary embodiment of an inductive heater;





FIG. 2

is another exemplary embodiment of an inductive heater;





FIG. 3

is an exemplary embodiment of a control circuit for use with an inductive heater;





FIG. 4

is an exemplary embodiment of an inductive heater with a concentrator sleeve;





FIG. 5

is a top view of an exemplary concentrator sleeve surrounding a capillary tube;





FIG. 6

is a schematic of an exemplary embodiment of an aerosol generator; and





FIG. 7

is a cross section of an exemplary embodiment of an aerosol generator.











DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS




The invention provides an inductively heated arrangement for forming an aerosol. In particular, inductive heating is used to heat fluid to temperatures high enough to volatize the fluid. The volatized fluid is then released or expelled from the device such that when the vapor comes in contact with the cooler air outside the device, the vapor forms into miniature droplets that create an aerosol.




In order for the inductive heater to heat the fluid, a current is passed through one or more inductive heating coils which produces an electromagnetic flux. A heating element is located such that the flux produces eddy currents inside the heating element which in turn heats the heating element. This heat is then transferred to a fluid by way of direct or indirect thermal conduction.





FIG. 1

shows details of an inductive heater


100


which can be used for heating fluid within a fluid passage


120


. The fluid can be supplied to the passage


120


by a fluid source


150


. The inductive heater


100


is a solenoidal inductive heater which includes excitation coils


110


wrapped around a coil bobbin


130


and a high frequency driver


160


supplies electric current to the coils


110


. The coil bobbin


130


has a tubular structure


131


with two circular pieces


132


and


133


located on each end that extend from the tubular center piece


131


. The coil bobbin


130


can be made of any suitable material, preferably a non-magnetic and non-electrically conductive material such as plastic or ceramic materials, e.g., a high temperature material.




Located through the middle of the center tubular piece


131


of the coil bobbin


130


is an electrically conductive heating element, which in

FIG. 1

is a tube


122


(e.g., a metal tube or composite tube such as a glass tube including a metal coating or layer) which forms a fluid passage


120


. The fluid passage


120


is designed so fluid can enter at one end, flow through the passageway and then exit at the other end. In operation, fluid in the fluid passage


120


is inductively heated to vaporize the fluid.




The fluid source


150


can be any fluid source capable of providing fluid to the fluid passage


120


. The fluid source can be integrally formed with the inductive heater or be an external component that is removable and replaceable. The fluid source


150


can provide fluid to the fluid passage


120


by numerous means, including, but not limited to, using pressure differences to force fluid into the passage, gravity, etc.




In the operation of the inductive heater, electrical current is sent through the excitation coils


110


at a predetermined frequency. The current through the wound excitation coils


110


creates a magnetic field. The flux from this magnetic field is coupled in the fluid passage


120


. As the flux enters the fluid passage


120


, eddy currents created in the electrically conductive tube


122


heat the tube which then transfers that heat to the fluid in the passage. The inductive heating of the heating element heats the fluid to a desirable temperature range in a rapid manner. In order for eddy currents to be created by magnetic coupling, the tube


122


is preferably made of an electrically conductive material, such as stainless steel. The frequency used can be any suitable frequency, e.g., in the range between 20 KHz to 1 MHz. The frequency is determined based upon the desired skin depth heating zone. For example, if the walls of the tube are very thin, then the amount of penetration in the skin is very minimal and thus a higher frequency can be used than in the case where the walls of the tube are thick.




An air gap


140


is also shown in the inductive heater of FIG.


1


. This air gap serves the purpose of thermally insulating the heated fluid passage


120


. The air gap is preferably sized to accommodate thermal isolation and coupled power requirements, e.g., a smaller gap provides more efficient coupled power transfer to the target but less thermal isolation. If the coil bobbin


130


was in contact with the fluid passage


120


, then the coil bobbin


130


could create a heat sink and draw heat away from the fluid passage


120


, thereby decreasing the efficiency of the heating mechanism.




The excitation coils


110


in

FIG. 1

can be wound around the coil bobbin


130


in various configurations in order to operate under different design conditions. For example, the density of the excitation coils


130


on the right side of the coil bobbin


130


can be increased and decreased on the left side in order to create a greater concentration of flux at the right side than on the left and thus greater heating ability on the upstream portion of the fluid passage. Likewise, for an opposite effect, the density of coils at the downstream portion of the fluid passage could be greater than at the upstream end.




Advantages of using inductive heating include simplicity in design in targeting a specified region of the fluid passage


120


and the ability to provide uniform heating to the targeted area. Preferred tube shapes for providing this uniform heating in inductive heating applications in the fluid passage


120


include circular, oval and polygonal (e.g., square shaped) tube shapes. In a circular tubular shape the eddy currents created are relatively uniform around the region being heated, thus creating a uniformly heated region. Polygonal shapes can also provide relatively uniform heating despite a slightly higher increase in temperature in the corners of the tube.




One advantage of the inductive heater is it's adaptability. That is, because heating of fluids in the fluid passage may lead to buildup of particles on the inner walls of the passage


120


creating an obstruction, it may be desirable from time to time to replace the tube


122


of an aerosol device with another tube. With such an arrangement, the aerosol generator could be used to form aerosols from different fluid chemistries, e.g., fluids containing different medicaments. Thus, the tube


122


can be designed so that it can be removed from the aerosol generator and replaced with another tube of the same or different dimensions.




Another way to utilize inductive heating is to use a toroid geometry such as that shown in

FIG. 2

instead of a solenoid geometry. The inductive heater of

FIG. 2

can be operated in a manner similar to the inductive heater of

FIG. 1

except that it uses a toroid


250


instead of a solenoid. The coil bobbin


230


holds the toroid


250


in the appropriate position and the fluid passage


120


is located through the center of the coil bobbin


230


and toroid


250


, e.g., tube


120


is fitted in seals


260


. The excitation coils


210


are wrapped around the core of the toroid


250


. The core of the toroid


250


is preferably made of soft iron or ferrite materials in order to enhance the flux concentration. It should be noted that other coil designs, besides those shown in

FIGS. 1 and 2

can be used in the inductive heater. For example, the coils can be flat and spiral inward. Such spiral coils can be placed over the surface of the heating element, heating that region of the heating element.





FIG. 3

is an exemplary power circuit


300


for powering the inductive heater. The power circuit


300


is shown connected to a toroid design inductive heater. In

FIG. 3

, the excitation coils


370


are shown wrapped around a core and the fluid passage


120


is shown located between the center of the toroid. The power circuit shown is a FET power bridge which is just one example of various types of circuits that may be used to power the inductive heaters of the present invention. The power supply can be a 5-15 Volt DC source and a convertor can provide an AC current through the toroid. This can be accomplished by use of the switches and forcing current to flow in opposite directions to simulate AC current as seen by the toroid. For example, switches


341


and


344


turn on so that current flows through the resonant capacitor


350


, through the toroid, back through the second resonant capacitor


360


and through switch


344


. When switches


342


and


343


open and


341


and


344


are closed, current flows in the opposite direction. Thus, a simulation of AC current is obtained as seen by the toroid. Although a toroid inductive heater is shown in

FIG. 3

, a solenoid inductive heater could also be used with the power circuit.




Another exemplary embodiment of an inductive heater is shown in FIG.


4


. The inductive heater of

FIG. 4

includes solenoidal excitation coils


410


and a flux concentrator


440


. The flux concentrator


440


is positioned between the fluid passage


120


and the excitation coils


410


. The shape of the flux concentrator


440


can be the same as that of the fluid passage


120


, e.g. the tube


122


and the concentrator


440


can be concentric cylinders. In the embodiment shown, the flux concentrator


440


comprises a sleeve which fits on spacers


430


and the tube


122


is removably mounted in aligned openings in the spacers


430


. In this way, the flux concentrator


440


is spaced a predetermined distance away from the tube


122


.




The performance of the solenoidal inductive heater can be enhanced with the use of the flux concentrator


440


. That is, the coupled power can be increased by two to three or more times compared to the coupled power without the flux concentrator


440


. The flux concentrator


440


also further reduces EMI emissions. The flux concentrator


440


can be composed of any material that will concentrate the flux from the excitation coils


410


. Preferably, a ferrite element is used as a flux concentrator because of its commercial availability and low cost.





FIG. 5

is an exemplary embodiment of the flux concentrator


440


showing the positioning of the flux concentrator


440


as it surrounds the fluid passage


120


. The flux concentrator


440


can be made as one single sleeve that slides over the fluid passage


120


or it can be made of separate pieces (e.g., two semicylindrical pieces), as shown in

FIG. 5

, that fit together to form the sleeve.




An advantage of the inductive heater is that it can heat the fluid in passage


120


without coming into contact with the fluid, thereby avoiding contamination of the fluid and/or buildup of deposits on the heater. Further, the non-contact feature allows the heater to be used with different fluid passage designs and/or replaceable fluid conduits such as stainless steel or metal coated glass tubular fluid delivery systems.




In each of the above inductive heaters, the number of coil turns affect the heating rate and the focusing of heat on an area in the fluid passage


120


. Increasing the number of coil turns will increase the amount of flux through the fluid passage


120


whereby it is possible to decrease the amount of time it takes to heat the fluid passage


120


.




The principle of increasing coil turns can be applied to focus heat on one or more areas of the fluid passage


120


. This is accomplished by winding more excitation coils around the area(s) where heat is to be focused. Thus, more flux can be concentrated on a specified area to provide more heat to that area.




In another exemplary embodiment, the aerosol generator can be fabricated using microelectronic mechanical systems (MEMS) technology. The MEMS technology utilizes fabrication techniques that are known such as for fabrication of semiconductor devices. Using this technology, the fluid passage can comprise a channel in a multilayered composite. The layer can be of any suitable material such as metal, plastic or ceramic material. For example, the fluid passage can be etched into a layer of ceramic material such as alumina, the heating element can be formed by depositing a metal layer in the channel or on another layer of material, and the layers can be attached together by any suitable technique such as adhesive bonding, brazing, etc. The resulting composite thus provides a fluid passage by way of the channel and a heating element by way of the metal layer. The heating element can be located in an inductive excitation coil arrangement and when fluid is supplied to the channel, the excitation coil arrangement can inductively heat the heating element to vaporize the fluid.





FIG. 6

shows a vapor driven aerosol generator


600


which can incorporate the inductive heating arrangement in accordance with the invention. As shown, the aerosol generator


600


includes a source


612


of fluid, a valve


614


, an optional chamber


616


, a valve


618


, a passage


620


, a mouthpiece


622


, an optional sensor


624


and a controller


626


. In addition, the aerosol generator


600


includes an optional preheater element


628


and a main heater element


630


. The controller


626


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


614


,


618


, the sensor


624


and excitation coils for heating the heating elements


628


,


630


. In operation, the valve


614


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


612


to enter the chamber


616


during which time the valve


618


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


620


. Filling of the chamber


616


can occur prior to or subsequent to detection by the sensor


624


of vacuum pressure applied to the mouthpiece


622


by a user attempting to inhale aerosol from the inhaler


600


. Once the chamber


616


contains a predetermined volume of fluid, the controller


626


closes valve


614


and opens valve


618


while operating an excitation coil (not shown) to inductively heat the preheater element


628


to drive the fluid into the passage


620


. While the fluid passes through the passage


620


, the controller


626


operates another excitation coil (not shown) to inductively heat the main heater element


630


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


632


of the passage


620


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


622


.





FIG. 7

shows a top cut-away view of a vapor driven aerosol generator


700


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


700


includes a fluid supply


742


, a chamber


744


, a fluid passage


746


, a preheater element


748


and a main heater element


750


. The preheater element


748


can be arranged on one side of the chamber


744


such that fluid in the chamber


744


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


744


into the passage


746


. If desired, an additional preheater element


752


can be provided in the chamber


744


in order to provide additional heating of the fluid. The main heater element


752


can be inductively heated by an excitation coil (not shown) to form a volatilized fluid which exits the passage


746


and forms an aerosol. Further, operation of the excitation coils and supply of fluid from the fluid source


742


can be controlled by a suitable controller as shown in the embodiment of FIG.


6


.




While this invention has been described in conjunction with the exemplary embodiments outlined above, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, the exemplary embodiments of the invention may be made without departing from the spirit and scope of the invention.



Claims
  • 1. An aerosol generator, comprising:a capillary fluid passage having an upstream end adapted to receive fluid from a fluid supply; and an inductive heater comprising at least one excitation coil and at least one heating element located along the fluid passage, the excitation coil being adapted to form an electromagnetic field which causes the heating element to heat fluid in the fluid passage such that the fluid is vaporized and forms an aerosol after exiting the fluid passage.
  • 2. The aerosol generator of claim 1, wherein the excitation coil comprises a solenoid coil or the coil is toroidal shaped.
  • 3. The aerosol generator of claim 1, wherein the heating element comprises an electrically conductive tube.
  • 4. The aerosol generator of claim 3, wherein the tube is made of stainless steel.
  • 5. The aerosol generator of claim 1, wherein the fluid passage is a channel in a composite.
  • 6. The aerosol generator of claim 1, wherein the vaporized fluid exits at one end of the fluid passage through a restricted opening.
  • 7. The aerosol generator of claim 1, wherein the excitation coil is located adjacent a downstream end of the fluid passage.
  • 8. The aerosol generator of claim 1, wherein the excitation coil is driven by an electronic driver circuit.
  • 9. The aerosol generator of claim 8, wherein the electronic driver circuit is powered by 5-15 volts.
  • 10. The aerosol generator of claim 1, wherein the fluid passage is located in a multilayered composite.
  • 11. The aerosol generator of claim 1, further comprising:a mouthpiece through which a user inhales the aerosol; and a pressure sensor adapted to detect a vacuum pressure applied to the mouthpiece by the user.
  • 12. The aerosol generator of claim 1, further comprising:a valve operable to control entry of the fluid into the fluid passage from the fluid supply; and a controller operable to control the operation of the valve.
  • 13. An aerosol generator, comprising:a fluid passage extending through a tube removably mounted in the aerosol generator, the fluid passage having an upstream end adapted to receive fluid from a fluid supply; and an inductive heater comprising at least one excitation coil and at least one heating element located along the fluid passage, the excitation coil being adapted to form an electromagnetic field which causes the heating element to heat fluid in the fluid passage such that the fluid is vaporized and forms an aerosol after exiting the fluid passage.
  • 14. An aerosol generator, comprising:a fluid passage having an upstream end adapted to receive fluid from a fluid supply; and an inductive heater comprising at least one excitation coil wound on a bobbin surrounding the fluid passage and at least one heating element located along the fluid passage, the excitation coil being adapted to form an electromagnetic field which causes the heating element to heat fluid in the fluid passage such that the fluid is vaporized and forms an aerosol after exiting the fluid passage.
  • 15. An aerosol generator, comprising:a fluid passage having an upstream end adapted to receive fluid from a fluid supply; an inductive heater comprising at least one excitation coil and at least one heating element located along the fluid passage, the excitation coil being adapted to form an electromagnetic field which causes the heating element to heat fluid in the fluid passage such that the fluid is vaporized and forms an aerosol after exiting the fluid passage; and a flux concentrator positioned so as to increase the amount of flux created by the electromagnetic field that passes through the heating element.
  • 16. The aerosol generator of claim 15, wherein the flux concentrator is positioned between the excitation coil and fluid passage.
  • 17. The aerosol generator of claim 15, wherein the flux concentrator is made of multiple pieces of flux concentrating material that extend around the heating element.
  • 18. The aerosol generator of claim 15, wherein the flux concentrator is made of a single piece of flux concentrating material that surrounds the heating element.
  • 19. A method for generating an aerosol, comprising:supplying fluid to a capillary fluid passage in which fluid flows from an upstream end of the fluid passage to a downstream end of the fluid passage; heating a heating element by induction heating such that fluid in at least a portion of the fluid passage is vaporized; and expanding the vaporized fluid out of the fluid passage and forming an aerosol.
  • 20. The method of claim 19, wherein the heating is carried out using a solenoidal coil or a toroidal coil.
  • 21. The method of claim 19, wherein the vaporized fluid passes through a small outlet at the downstream end of the fluid passage.
  • 22. The method of claim 19, wherein the capillary tube comprises an electrically conductive material and the heating is carried out by inductively generating eddy currents on a surface of the capillary tube.
  • 23. The method of claim 19, wherein the fluid passage is located in a multilayered composite.
  • 24. A method for generating an aerosol, comprising:supplying fluid to a fluid passage extending through a tube removably mounted in an aerosol generator, the fluid flowing from an upstream end of the fluid passage to a downstream end of the fluid passage; heating a heating element by induction heating such that fluid in at least a portion of the fluid passage is vaporized; and expanding the vaporized fluid out of the fluid passage and forming an aerosol.
  • 25. A method for generating an aerosol, comprising:supplying fluid to a fluid passage in which fluid flows from an upstream end of the fluid passage to a downstream end of the fluid passage; heating a heating element by induction heating using a flux concentrator which extends around the fluid passage such that fluid in at least a portion of the fluid passage is vaporized; and expanding the vaporized fluid out of the fluid passage and forming an aerosol.
  • 26. A method for generating an aerosol, comprising:supplying fluid to a fluid passage in which fluid flows from an upstream end of the fluid passage to a downstream end of the fluid passage; heating a heating element by induction heating using a solenoidal coil or a toroidal coil such that fluid in at least a portion of the fluid passage is vaporized; increasing the amount of flux created by the electromagnetic field that passes through the heating element with a flux concentrator; and expanding the vaporized fluid out of the fluid passage and forming an aerosol.
  • 27. The method of claim 26, wherein the flux concentrator is positioned between the coil and fluid passage.
  • 28. The method of claim 26, wherein the flux concentrator is made of multiple pieces of flux concentrating material that extend around the heating element.
  • 29. The method of claim 26, wherein the flux concentrator is made of a single piece of flux concentrating material that surrounds the heating element.
US Referenced Citations (207)
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
4558196 Babasade Dec 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
4764660 Swiatosz Aug 1988 A
4771563 Easley Sep 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
5117482 Hauber May 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
5211845 Kaneshige May 1993 A
5217004 Blasnik et al. Jun 1993 A
5222185 McCord, Jr. 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
5810988 Smith et al. Sep 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
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
5990465 Nakaoka 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
6147336 Ushijima 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 International Preliminary Examination Report for PCT/US01/44812 dated Mar. 4, 2003.
Written Opinion for PCT/US01/44812 dated Sep. 26, 2002.
Notification of Transmittal of the International Search Report or the Declaration Dated May 10, 2002 for PCT/US01/44812.
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.