WO2003097126A2 - Aerosol for medical treatment and methods - Google Patents
Aerosol for medical treatment and methods Download PDFInfo
- Publication number
- WO2003097126A2 WO2003097126A2 PCT/US2003/015891 US0315891W WO03097126A2 WO 2003097126 A2 WO2003097126 A2 WO 2003097126A2 US 0315891 W US0315891 W US 0315891W WO 03097126 A2 WO03097126 A2 WO 03097126A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- bonding material
- vibratory element
- actuator
- aerosol generator
- layer
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M15/00—Inhalators
- A61M15/0085—Inhalators using ultrasonics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M11/00—Sprayers or atomisers specially adapted for therapeutic purposes
- A61M11/005—Sprayers or atomisers specially adapted for therapeutic purposes using ultrasonics
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
- B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
- B05B17/00—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups
- B05B17/04—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods
- B05B17/06—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations
- B05B17/0607—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers
- B05B17/0638—Apparatus for spraying or atomising liquids or other fluent materials, not covered by the preceding groups operating with special methods using ultrasonic or other kinds of vibrations generated by electrical means, e.g. piezoelectric transducers spray being produced by discharging the liquid or other fluent material through a plate comprising a plurality of orifices
- B05B17/0646—Vibrating plates, i.e. plates being directly subjected to the vibrations, e.g. having a piezoelectric transducer attached thereto
Definitions
- This invention relates generally to the field of pulmonary drug delivery, and in particular to the aerosolizing of liquid medicament into fine liquid droplets for inhalation.
- aerosol generators can be subjected to a variety of environmental conditions, many of which can threaten to degrade the performance of the generator; for instance, during operation, the piezo and/or the electrodes may be in danger of exposure to the fluid being aerosolized.
- the piezo and/or the electrodes may be in danger of exposure to the fluid being aerosolized.
- Those skilled in the art will recognize that, in many cases, prolonged exposure to such fluids can result in corrosion of the piezo and/or the electrodes, and even relatively brief exposure can vitiate the electrical communication between the piezo and the circuitry by which it is driven (for example, by short-circuiting the electrodes and/or otherwise interfering with the electrical communication between the electrodes and the piezo).
- aerosol generators are used in hospitals and/or other institutional settings, where strict sanitization policies often are enforced to prevent cross-infection by multiple users of a generator.
- aerosol generators may be exposed to potentially corrosive substances, such as solvents and disinfectants.
- generators may be exposed to relatively high levels of heat, pressure, and/or humidity during sanitization processes, such as autoclaving and the like. Without protection, therefore, the relatively sensitive components of aerosol generators (including, for example, their piezos and/or electrodes) may be damaged during sanitization and/or the operational lives of such components may be limited significantly by repeated sanitization procedures.
- Embodiments of the invention therefore, address certain limitations in the prior art and include apparatus and methods for aerosolizing liquid.
- one embodiment of the invention provides an apparatus for generating an aerosol.
- the apparatus includes an actuator having a first face and a second face and defining an opening therethrough, as well as a vibratory element in mechanical communication with the actuator, and a sealing member configured to isolate the vibratory element from a surrounding environment.
- the apparatus further comprises an aerosolization element mounted on the actuator and disposed substantially over the opening, wherein the aerosolization element defines at least one aperture therethrough.
- the vibratory element may be operated to vibrate to cause movement of the aerosolization element in such a manner that a liquid at the first face of the aerosolization element can be dispensed as an aerosol through the at least one aperture.
- Some embodiments feature an electrode coupled to the vibratory element.
- the vibratory element is annular in shape and/or comprises a piezoelectric ceramic
- the sealing element is annular, such that it covers at least a portion of the first face of the actuator, at least a portion of the second face of the actuator, and at least a portion of the vibratory element.
- the sealing element can comprise an elastomer and/or a rubber, which can be, merely by way of example, a synthetic rubber or a silicone.
- the sealing member can be molded around at least a portion of the vibratory element, and can be formed by injection molding.
- Some embodiments include one or more layers of bonding material between the sealing element and the vibratory element.
- the bonding material can couple the sealing member relatively securely to at least one of the vibratory element and the actuator and can, in some cases, provide a relatively impervious barrier between the electrode and the surrounding environment.
- the bonding material can be relatively impervious to a relatively severe environmental condition, which can include, ter alia, heat, humidity, pressure, alternating cycles of vacuum and pressure, and a corrosive chemical.
- Figure 2 a side cross-sectional view of an aerosol generator assembly, in accordance with various embodiments of the present invention.
- Figure 3 is a bottom view of an aerosol generator assembly, in accordance with various embodiments of the present invention.
- Figure 4 is a side view of an aerosol generator assembly, in accordance with various embodiments of the present invention.
- FIG. 5 is a top perspective view of an aerosol generator assembly, in accordance with various embodiments of the present invention.
- Figures 8A and 8B illustrate a portion of an aerosol generator assembly with a 0 plurality of layers of bonding materials, in accordance with various embodiments of the invention.
- FIGS 9A and 9B illustrate a portion of an aerosol generator assembly having an adhesive situated between an actuator and a vibratory element, in accordance with various embodiments of the invention.
- Figure 10 illustrates a cross section of an aerosol generator assembly having a single layer of bonding material applied to portions of a vibratory element, in accordance with various embodiments of the invention.
- Figure 11 illustrates a cross section of an aerosol generator assembly having a single layer of bonding material applied to portions of a vibratory element, an actuator and an -0 aerosolization element, in accordance with various embodiments of the invention.
- Figure 13 illustrates a cross section of an aerosol generator assembly having an adhesive disposed between a vibratory element and an actuator, in accordance with various embodiments of the invention.
- Figure 14 illustrates a cross section of an aerosol generator assembly having an adhesive disposed between a vibratory element and an actuator, a first layer of bonding 0 material applied to portions of the vibratory element, and a second layer of bonding material applied to portions of the vibratory element, the actuator, and an aerosolizing element, in accordance with various embodiments of the invention.
- Figure 16 illustrates a cross section of an aerosol generator assembly having an adhesive disposed between a vibratory element and an actuator and first layer of bonding material applied to portions of the vibratory element, the actuator, and an aerosolization element, in accordance with various embodiments of the invention.
- Figure 17 illustrates a cross section of an aerosol generator disposed within a mold assembly, in accordance with embodiments of the invention.
- Figure 18 illustrates a detail view of the aerosol generator and mold assembly of Figure 17.
- Figure 19 illustrates a process flow diagram for producing an aerosol generator assembly in accordance with various embodiments of the invention.
- an aerosol generator assembly comprising an aerosol generator and an sealing element overmolded onto the aerosol generator.
- an aerosol generator comprises a piezoelectric and/or piezomagnetic vibratory element (a "piezo") for vibrating an aerosolization element to aerosolize a fluid.
- the piezoelectric member is driven by application of an electric and/or magnetic field, which often is supplied through an electric circuitry coupled to the piezo by one or more electrodes.
- a sealing member in accordance with some embodiments comprises a thermoplastic elsastomer known in the art as SantopreneTM, which is commercially available from Advanced Elastomer Systems, L.P., of Akron, Ohio, USA.
- SantopreneTM thermoplastic elsastomer known in the art as SantopreneTM
- the sealing member can be formed by a variety of techniques, including for example, injection molding.
- U.S. Pat. No. 6,554,201 the entire disclosure of which is incorporated herein by reference for all purposes, describes one exemplary injection molding process that can be used in conjunction with aerosol generators.
- the sealing member can be used as a mounting apparatus for coupling the aerosol generator to a housing.
- aerosol generators often are mounted within a housing for operation, such that the housing can provide (and/or be in communication with) a supply of fluid to be aerosolized, such as a chamber and/or the like.
- the housing can also be an integrated part of a nebulizer system, such that it provides fluid communication between the aerosol generator and a patient's airway, either passively (such as, for instance, in an inhaler, where the patient inhales the aerosolized fluid from the housing) and/or actively (such as, for instance, when the housing is part of a respirator system).
- the sealing member which, as noted, can comprise a relatively elastic and/or flexible substance, can couple the aerosol generator to the housing securely enough to prevent dislodging of the generator, yet flexibly enough that the vibratory characteristics of the generator are not significantly impacted, thereby substantially maintaining the performance of the aerosol generator.
- one or more bonding materials can be applied between and/or among the sealing member and various components of the aerosol generator.
- bonding materials can include adhesives, epoxies, paints, primers and the like. Those skilled in the art will recognize that certain bonding materials can provide a relatively secure coupling between the aerosol generator and the overmold.
- the bonding materials can be selected based on their abilities to enhance the vibratory performance of the generator and/or create or reinforce a barrier between the piezo (and/or its electrodes) and the surrounding environment.
- the bonding materials are relatively impervious to environmental conditions to which aerosol generators commonly are exposed during operation, sanitization, etc.
- certain bonding materials can be relatively immune to an autoclave environment, which can introduce significantly elevated heat and pressure, along with relatively high levels of atmospheric water vapor and/or other fluids.
- certain bonding materials can be impervious to any corrosive effects of cleaning fluids and/or fluids to be aerosolized.
- the sealing member 104 can be formed in such a fashion as substantially to surround the piezo 120 and actuator 112, and can, as illustrated in Fig. 1, be cup-shaped and/or annular in shape as well.
- the sealing member 104 can be formed to have a relatively thick exterior portion that tapers to a relatively narrow interior portion, which can allow for more secure mounting in a housing without impacting the ability of aerosolized liquid to disperse away from the aerosolization element 108.
- the sealing member 104 can include one or more features (which may be integrally formed with the sealing member 104) to allow efficient coupling of the assembly 100 with the housing.
- Fig. 3 illustrates a bottom view of the aerosol generator assembly 100.
- the sealing member 104 can extend around the outer surface of the generator to encompass a portion of the bottom face of the aerosol generator. In some cases, a portion of bottom face of the actuator 112 may be left exposed, while in other cases, the sealing member 104 may extend inward across the bottom of the generator toward the actuator's central aperture, leaving only the aperture plate 108 exposed. Also as shown on Fig.
- the sealing member 104 may be formed to allow insertion of one or more electrical conduits 116 (e.g., insulated wires, etc.) through the sealing member 104 for coupling to a piezo, one or more electrodes, etc.
- the electrical conduits 116 can be attached to the aerosol generator before formation of the sealing member 104, such that the sealing member 104 is molded around the conduits 132.
- FIG. 4 illustrates a side view of the aerosol generator assembly 100, displaying the circumferential notch 128 described above, as well as the electrical conduits 132.
- Figs. 5 and 6 illustrate perspective drawings of the assembly 100, as seen from the top and bottom, respectively.
- FIG. 7 provides a cross-sectional illustration of an aerosol generator assembly 700 in accordance with other embodiments of the invention.
- the aerosol generator assembly 700 includes a sealing member 704 formed around an actuator 708 and a vibratory element 712 in mechanical communication with one another.
- the assembly 700 further includes an aerosolization element 716 mounted on the actuator 708 in a fashion similar to that described above.
- the sealing member 704 is generally annular in shape.
- Fig. 8 A illustrates a cross-sectional view of an aerosol generator assembly 800 in accordance with some embodiments of the invention.
- the assembly 800 features a sealing member 804 molded around an aerosol generator, which includes an actuator 808 in mechanical communication with a piezoelectric vibratory element 812.
- An aerosolization element 816 can be mounted on the actuator 808 and can be used to aerosolize a liquid in a manner similar to that discussed above.
- the actuator has a first face 820 and a second face 824.
- the actuator 808 can be annular, having an outer surface 828 and an inner surface 832, which can define a central aperture through the aperture 808. In some cases, the outer surface 828 can define a flange.
- the aerosolization element 816 can be mounted so as to cover substantially the central aperture, and the aerosolization element 816 itself can have one or more apertures through which the aerosolized material can flow.
- the vibratory element 812 can be in mechanical communication with the actuator 808.
- the vibratory element 812 can be mechanically coupled to the actuator 808 through a variety of means.
- the vibratory element 812 can be bonded to the actuator 808 with an adhesive 836.
- the vibratory element 812 may be attached with mechanical fasteners to the actuator 808.
- the vibratory element 812 and the actuator 808 may be integrally formed, perhaps from the same material. In certain embodiments, as shown in Fig.
- the vibratory element 812 may be configured in a ring of rectangular cross-section, having an outer surface 840 and an inner surface 844, and the adhesive can be placed adjacent to either surface 840, 844, or both, to provide mechanical coupling between the vibratory element 812 and the actuator 808.
- the vibratory element can also have a first face 852 and a second face 856, and one or more electrodes 860 may be mounted on either face 852, 856, or both.
- a bonding material for instance, an adhesive
- one or more layers of bonding material may be disposed between and/or among the sealing member 804 and various components of the aerosol generator.
- one such bonding material may be an adhesive 844.
- Other bonding materials can include paints, epoxies, primers, and the like, as discussed herein.
- a first layer of bonding material 864 can be applied over the second face 856 of the vibratory element 812 and/or the electrode 860.
- the first layer 864 additionally can be disposed over any adhesive 836 adjacent to the outer 840 and/or inner 844 surfaces of the vibratory element. In some cases, as shown in Figs.
- the adhesive 836 can be tapered, such that the first layer 864 can be applied to the point where the adhesive tapers to be flush with the actuator 808, forming a barrier over the vibratory element 812, the electrode 860, and any adhesive 836.
- any of the bonding materials used herein can be applied as the first layer 864.
- the first layer 864 can be a paint and/or an epoxy.
- the sealing member 804 can comprise an elastomer, including any of those discussed above.
- the sealing member 804 may comprise silicone.
- a silicone that may be used in accordance with the present invention is a two part silicone, available from a company known as Wacker-Chemie GmbH, Geschafts Rail Silicone, Hanns-Seidel-Platz 4, D-81737 Muchen (Munich, Germany). Such silicone is known to be described in a product description captioned "Elastosil ® LR 3003 / 10 A, B ⁇ LR 3003 / 80 A, B.”
- One variety of such silicone that may be used in accordance with the present invention is designated as 40 Shore, representative of relative hardness of the cured silicone.
- a layer of primer (which can be thought of as one of the layers 868 in Fig. 8A) may be applied to surfaces of the aerosol generator receiving the overmold, which can include the vibratory element, the electrode, the portions of the actuator, and a portion of the aerosolization element, such as the flange, or part of the flange.
- the primer may be applied to cover a slightly larger area than the overmold, to ensure that there is sufficient coverage of the primer to maximize bonding of the overmold.
- a primer that may be used in accordance with the present invention is known as CF6-135 High Technology Silicon Primer (Clear) available from a company known as NuSil Technology, Carpenteria, California, USA.
- a layer of epoxy (which can be thought of as the first layer 864 in Fig. 8 A) may be applied to the exposed surfaces of the vibratory element .
- This layer can be applied prior to the application of a primer, or may be applied without the addition of a primer.
- the painted epoxy may comprise an autoclavable epoxy, such as, for example, a product designated as Masterbond EP3HTMED by a company known as Masterbond of New York, USA.
- the epoxy paint may be applied in a first layer and a second layer. In such case, it may be applied at room temperature with a fine point paintbrush. It may be cured at 130 degrees C for 30 minutes, whereupon a second application may be applied at room temperature, and likewise cured at 130 degrees C for 30 minutes.
- any bonding material can be relatively small compared to the size of the aerosol generator and sealing member.
- each bonding material may range from approximately a nanometer to approximately several micrometers in thickness, depending on the material used. Accordingly, in the various figures accompanying this application, the paint and primer thickness are enlarged for purposes of illustration.
- FIGS 9A and 9B illustrate how an adhesive may be used in accordance with some embodiments of the invention.
- An aerosol generator assembly 900 may be formed of a sealing member 904 molded around an aerosol generator, which can comprise a vibratory element 908, an actuator 912 and an aerosolizing element 916.
- a relatively thin layer of adhesive 920 which can be an epoxy adhesive, can be disposed between the vibratory element 908 and the actuator 912. Excess adhesive may adhere to the sides of the vibratory element 908, and, in this way, can be used to provide a more secure fit between the sealing member 904 and the aerosol generator.
- any additional bonding materials as the adhesive 920 and sealing member act to provide a relatively impervious barrier between the surrounding environment and the vibratory element 908 (and, optionally, one or more electrodes, which are not shown in Figs. 9 A and 9B).
- FIGs. 10-16 illustrate several different embodiments of the invention, employing a variety of bonding materials between and among the sealing member and various components of the aerosol generator.
- each of Figs. 10-16 omit the electrodes, but those skilled in the art will appreciate, based on the disclosure herein, that electrodes could be incorporated as desired into each of the illustrated embodiments.
- an aerosol generator assembly 1000 is illustrated.
- the assembly includes a single layer 1004 of bonding material, which can be primer, paint, epoxy, etc., applied to the top face and each side face of a vibratory element 1008, which is mounted on an actuator 1012.
- the bonding material 1004 in conjunction with the actuator 1012, completely surrounds the vibratory element.
- a layer of bonding material 1104 has been applied not only to surround the upper, inner and outer surfaces of the vibratory element 1008, but also has been applied to portions of the actuator 1012 (including the flange and bottom surface thereof), as well as to portions of the aerosolizing element 1016.
- the bonding material 1104 has been applied to every surface of the aerosol generator with which the sealing member 1020 comes into contact.
- Fig. 12 illustrates an aerosol generator assembly 1200 employing a first layer 1204 and a second layer 1208 of bonding material.
- the first layer 1204 has been applied to the top, inner and outer surfaces of the vibratory element 1008, similar to layer 1004 in Fig. 10.
- the second layer 1208 is applied over the top of the first layer 1204 and also to portions of the actuator 1216 (including, again, portions of the flange and bottom surfaces of the actuator), as well as to the outer portion of the aerosolizing element 1016. Hence, like the layer 1104 in Fig. 11, the second layer 1208 has been applied to every surface of the aerosol generator with which the sealing member 1020 comes into contact.
- FIG. 13 illustrates an embodiment of an aerosol generator assembly 1300 similar to that discussed with respect to Figs. 9 A and 9B, in which the bonding material 1304 (perhaps an adhesive) is applied between the vibratory element 1008 and the actuator 1012.
- the assembly 1400 of Fig. 14 includes the adhesive 1304 between the vibratory element 1008 and the actuator 1012, as well as additional layers 1404 and 1408, which can be thought of as similar to layers 1204, 1208 respectively, illustrated in Fig. 12.
- Fig. 15 illustrates an aerosol generator assembly 1500 in which a layer of adhesive 1504 is disposed between the vibratory element 1008 and the actuator 1012.
- a layer 1516 of bonding material overlays the adhesive 1504 and the vibratory element 1008, such that the adhesive 1504 and the layer 1516 of bonding material together function to completely encapsulate the vibratory element 1008.
- the assembly 1600 of Fig. 16 is similar to the assembly 1500 of Fig. 15, except that the layer of bonding material 1604 is applied not only to the adhesive 1504 and the vibratory element 1008, but also to portions of the actuator 1012 and aerosolizing plate 1016, effectively coating each surface that will be in contact with the sealing member 1020.
- Fig. 17 illustrates an exemplary mold assembly 1700 for molding a sealing member onto an aerosol generator, in accordance with embodiments of the invention.
- the mold assembly 1700 is designed to accept an aerosol generator 1704 and defines a cavity 1708 into which mold material may be placed.
- the cavity defines the shape of the sealing member to be molded.
- the mold material may comprise any of the materials discussed above with regards to the composition of a sealing member.
- the mold material is capable of being injection molded.
- the mold material can be in a liquid or semi-liquid form.
- the mold material can be placed into the cavity 1708 through any suitable method known in the art, including merely by way of example, injection molding via channel 1712.
- the mold assembly 1700 can comprise multiple components 1716a-d, which can be disassembled after the sealing member has hardened and/or cured, to allow for easy removal of the finished article.
- Fig. 18 illustrates a detail drawing of the mold assembly 1700 after mold material 1800 has been injected into the cavity.
- FIG. 19 One exemplary embodiment 1900 is illustrated by Fig. 19. It should be noted that, while the procedures in method 1900 are illustrated and discussed in a certain order for ease of description, embodiments of the invention are not limited to any particular order.
- the method 1900 comprises providing a aerosol generator (block 1904), which can, in some embodiments, include any of the aerosol generators discussed herein.
- the aerosol generator can be prepared to receive a bonding material and or to be molded with a sealing member. Preparation can include, inter alia, priming, scoring, chemical etching, and the like.
- a layer of bonding material such as adhesive, epoxy, paint, primer and/or the like can be applied, and at block 1916 that layer can be cured. In some cases, the application of the bonding material can be done by dipping, paintbrush, airbrush, and/or other known application techniques.
- the curing process can take place at a relatively high temperature, for a specified period of time.
- the application (block 1912) and/or curing (block 1916) procedures can be repeated as necessary to produce multiple layers of bonding material and/or a single, thicker layer of material.
- the aerosol generator can be placed within a mold assembly, and at block 1924, mold material may be placed into one or more appropriate cavities in the mold assembly.
- block 1924 can include any appropriate procedure, including injection molding, packing, and the like.
- the mold material can then be allowed to form (e.g., cure, harden, etc.) to produce a sealing member molded onto the aerosol generator (block 1928), at which point the finished aerosol generator assembly can be removed from the mold assembly (block 1932).
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP03753105.0A EP1509259B1 (en) | 2002-05-20 | 2003-05-20 | Apparatus for providing aerosol for medical treatment and methods |
AU2003256253A AU2003256253A1 (en) | 2002-05-20 | 2003-05-20 | Aerosol for medical treatment and methods |
ES03753105.0T ES2572770T3 (en) | 2002-05-20 | 2003-05-20 | Apparatus for providing spray for medical treatment and methods |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US38225602P | 2002-05-20 | 2002-05-20 | |
US60/382,256 | 2002-05-20 |
Publications (2)
Publication Number | Publication Date |
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WO2003097126A2 true WO2003097126A2 (en) | 2003-11-27 |
WO2003097126A3 WO2003097126A3 (en) | 2004-08-05 |
Family
ID=29550178
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2003/015891 WO2003097126A2 (en) | 2002-05-20 | 2003-05-20 | Aerosol for medical treatment and methods |
Country Status (5)
Country | Link |
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US (2) | US6915962B2 (en) |
EP (1) | EP1509259B1 (en) |
AU (1) | AU2003256253A1 (en) |
ES (1) | ES2572770T3 (en) |
WO (1) | WO2003097126A2 (en) |
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- 2003-05-20 AU AU2003256253A patent/AU2003256253A1/en not_active Abandoned
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CN105903106B (en) * | 2015-05-12 | 2022-07-12 | 深圳瑞之谷医疗科技有限公司 | Medicine cup subassembly and medical atomizer |
Also Published As
Publication number | Publication date |
---|---|
US20050178847A1 (en) | 2005-08-18 |
EP1509259A4 (en) | 2007-03-28 |
EP1509259A2 (en) | 2005-03-02 |
WO2003097126A3 (en) | 2004-08-05 |
US20040050947A1 (en) | 2004-03-18 |
AU2003256253A8 (en) | 2003-12-02 |
EP1509259B1 (en) | 2016-04-20 |
US7771642B2 (en) | 2010-08-10 |
AU2003256253A1 (en) | 2003-12-02 |
US6915962B2 (en) | 2005-07-12 |
ES2572770T3 (en) | 2016-06-02 |
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