Patent Application
20070044792
This invention relates generally to the field of liquid dispensing, and in particular to the aerosolizing of fine liquid droplets. More specifically, the invention relates to aerosolization apparatuses having components designed to reduce galvanic corrosion when employed to produce such fine liquid droplets.
A great need exists for the production of fine liquid droplets. For example, fine liquid droplets are used in for drug delivery, insecticide delivery, deodorization, paint applications, fuel injectors, and the like. In many applications, it may be desirable to produce liquid droplets that have an average size down to about 0.5 μl. For example, in many medical applications, such a size is needed to insure that the inhaled drug reaches the deep lung.
Techniques for aerosolizing liquids are described in U.S. Pat. No. 5,261,601 and utilizes a perforate membrane disposed over a chamber. The perforate membrane comprises an electroformed metal sheet using a “photographic process” that produces apertures with a cylindrical exit opening.
Apparatuses and methods for producing fine liquid droplets also include those described U.S. Pat. Nos. 5,164,740; 5,586,550; and 5,758,637, the complete disclosures of which are herein incorporated by reference, describe exemplary devices for producing fine liquid droplets. These patents describe the use of aperture plates having tapered apertures to which a liquid is supplied. The aperture plates are then vibrated so that liquid entering the larger opening of each aperture is dispensed through the small opening of each aperture to produce the liquid droplets. Such devices have proven to be tremendously successful in producing liquid droplets.
Unfortunately many useful aerosolized compounds are made from corrosive liquid precursors. Solutions of liquid medicaments such as albuterol sulfate have low pHs (e.g., a pH of about 3.5 or less), which can quickly corrode the components of a aerosolizing apparatus that contains an aperture plate. Thus there is a need for aerosolization apparatuses that can operate for extended periods of time aerosolizing low pH, and other types of corrosive liquids. These and other issues are addressed by the present invention.
Embodiments of the invention include an apparatus for generating an aerosol. The apparatus may include a support member having a first face and a second face and defining an opening therethrough, where the support member includes a first material having a first galvanic potential. The apparatus may also include an aerosolization element mounted on the support member and disposed substantially over the opening, where the aerosolization element defines at least one aperture therethrough, and where the aerosolization element comprises a second material having a second galvanic potential that is substantially equal to the first galvanic potential of the first material. In some embodiments, the apparatus may include a vibratory element in mechanical communication with the support member, and a sealing member configured to isolate the vibratory element from a surrounding environment. The vibratory element may be operated to vibrate to cause movement of the aerosolization element in such a manner that a liquid at a first face of the aerosolization element can be dispensed as an aerosol through the at least one aperture. The sealing member may be made from an elastomer.
Embodiments of the invention also include an apparatus for generating an aerosol that includes a support member having a first face and a second face and defining an opening therethrough, where the support member comprises a first material having a first galvanic potential. The apparatus may also include an aerosolization element mounted on the support member and disposed substantially over the opening, where the aerosolization element defines at least one aperture therethrough, and where the aerosolization element includes a second material having a second galvanic potential that is substantially equal to the first galvanic potential of the first material. The apparatus may still further include a vibratory element in mechanical communication with the support member, where the vibratory element may be operated to vibrate to cause movement of the aerosolization element in such a manner that a liquid at a first face of the aerosolization element can be dispensed as an aerosol through the at least one aperture.
Embodiments of the invention still further include a method of aerosolizing a liquid medicament. The method may include the step of providing an aperture plate made of a first material and having a top surface and a bottom surface, and also having a plurality of apertures, where the aperture plate is mounted on a support member comprising a second material that has an opening such that the aperture plate covers the opening, and where the first and second materials have similar galvanic potentials. The method may also include supplying the liquid medicament to the bottom surface of the aperture plate, and vibrating the aperture plate to eject liquid droplets from the top surface of the aperture plate.
Additional embodiments and features are set forth in part in the description that follows, and in part will become apparent to those skilled in the art upon examination of the specification or may be learned by the practice of the invention. The features and advantages of the invention may be realized and attained by means of the instrumentalities, combinations, and methods described in the specification.
A further understanding of the nature and advantages of the present invention may be realized by reference to the figures which are described in remaining portions of the specification. In the figures, like reference numerals are used throughout several to refer to similar components. In some instances, a sub-label consisting of a lower case letter is associated with a reference numeral to denote one of multiple similar components. When reference is made to a reference numeral without specification to an existing sub-label, it is intended to refer to all such multiple similar components.
The invention relates to methods and apparatuses for generating aerosols that include nebulizer components with improved resistance to galvanic corrosion. Galvanic corrosion normally increases with an increasing difference in the galvanic potential (e.g., oxidation potential) between two solid materials that come in electrical contact through a strong electrolytic solution (e.g., a strongly acidic solution). Making a support member component and aerosolization element of the nebulizer at least in part from materials having similar (or identical) galvanic potentials reduces the level of galvanic corrosion in these components as they aerosolize acidic solutions of medicaments (e.g., medicaments dissolved in solutions of HCl and H2SO4).
For example, an embodiment of the aerosolization apparatus may include an aperture plate made from palladium-nickel alloy that is mounted on a steel washer that has been made from, or coated with, the same palladium-nickel alloy. When these components come in contact with an acidic liquid medicament, galvanic corrosion is minimized because the exposed areas of both components are made from materials having the same galvanic potential. In contrast, when a palladium-nickel aperture plate is mounted on an uncoated steel washer, the difference in galvanic potentials causes the washer to act like an anode (i.e., the steel is oxidized), and the aperture plate to act like a cathode, of an electrolytic cell. The oxidation and corrosion of the steel washer in the medicament solution will interfere with, and eventually stop the operation of the apparatus.
Embodiments of the aerosolizaiton apparatus may include a support member having a first face and a second face and defining an opening therethrough that is made from (or coated with) a first material with a first galvanic potential, and an aerosolization element, made or coated with the same material, or another material having a similar galvanic potential. The aerosolization element may be mounted on the support member and disposed substantially over the opening, wherein the aerosolization element defines at least one aperture therethrough.
The apparatus may also include a vibratory element in mechanical communication with the support member, and a sealing member configured to isolate the vibratory element from a surrounding environment. 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.
In accordance with certain embodiments, the vibratory element is annular in shape and/or comprises a piezoelectric ceramic. In other embodiments, the sealing element is annular, such that it covers at least a portion of the first face of the support member, at least a portion of the second face of the support member, and at least a portion of the vibratory element. In further embodiments, 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 support member 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, inter alia, heat, humidity, pressure, alternating cycles of vacuum and pressure, and a corrosive chemical.
In other embodiments, the bonding material can be selected from the group consisting of a paint, an epoxy, an adhesive and a primer, and the at least one layer of bonding material can comprise a first application of a first bonding material and a second application of a second bonding material. The first and second bonding materials can be the same bonding material. In further embodiments, the bonding material comprises an adhesive situated between the vibratory element and the support member. In some cases, the vibratory element comprises an inner surface and an outer surface, and the adhesive can be situated between the sealing element and at least a portion of at least one of the inner and outer surfaces of the vibratory element.
The present invention also relates to methods of making and/or using aerosol generator assemblies according to embodiments of the invention. One exemplary method for making an aerosol generator assembly comprises providing an aerosol generator, which can be similar to one of the aerosol generators discussed above. The method also includes providing a mold assembly formed to receive the aerosol generator, placing a mold material into the mold assembly, allowing mold material to form a sealing element about at least a portion of the aerosol generator and removing the aerosol generator from the mold assembly.
In some cases, placing the mold material into the mold assembly comprises injection molding the mold material. In other cases, the method includes preparing at least one of the vibratory element and the support member. Preparing the vibratory element and/or support member can comprise chemical etching of those components.
In certain embodiments, the method further comprises applying at least one layer of bonding material between the mold material and least one of the vibratory element and the support member. Applying at least one layer can include applying a layer of a first bonding material and applying a layer of a second bonding material. The first bonding material and the second bonding material can be the same bonding materials. One or more layers can be applied at room temperature and cured at a relatively high temperature for a specified period of time. The relatively high temperature is above about 100° C., more specifically between about 100° C. and about 150° C. In some cases, the relatively high temperature is between about 120° C. and about 140° C., and more specifically, about 130° C. In other cases, the specified period of time is between about 15 minutes and about 45 minutes.
Embodiments of the present invention include apparatus and methods for aerosolizing liquid. In accordance with one embodiment, an aerosol generator assembly is provided, comprising an aerosol generator and a sealing element overmolded onto the aerosol generator. Those skilled in the art will appreciate that, in accordance with certain embodiments of the invention, an aerosol generator comprises a piezoelectric and/or piezomagnetic vibratory element (a “piezo”) for vibrating an aerosolization element to aerosolize a fluid. In many cases, 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. The connection between the circuitry and the electrodes can be of any type that is operative to supply electric current to the piezo, including, for instance, conductive metal wires (optionally, with non-conductive insulation), conductive polymeric materials, and the like.
In accordance with some embodiments of the invention, a sealing member, which can comprise a variety of relatively impermeable and/or elastic substances (including, merely by way of example, elastomers, rubbers (both natural and synthetic), urethanes, silicon and the like) and can serve to isolate/protect the piezo and/or electrodes from the surrounding environment, which can sometimes include relatively severe environmental conditions, including without limitation, the conditions described below, such as relatively high heat, pressure, and atmospheric moisture, immersion in fluids, exposure to corrosive fluids, and the like.
Merely by way of example, a sealing member in accordance with some embodiments comprises a thermoplastic elsastomer known in the art as Santoprene™, which is commercially available from Advanced Elastomer Systems, L.P., of Akron, Ohio, USA. As described below, 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.
In other embodiments, the sealing member can be used as a mounting apparatus for coupling the aerosol generator to a housing. Those skilled in the art will recognize that 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. Additionally, 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). In some embodiments, therefore, 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.
In still other embodiments, one or more bonding materials can be applied between and/or among the sealing member and various components of the aerosol generator. In some cases, 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. Further, 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. In many cases, the bonding materials are relatively impervious to environmental conditions to which aerosol generators commonly are exposed during operation, sanitization, etc. For instance, as discussed below, 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. Likewise, certain bonding materials can be impervious to any corrosive effects of cleaning fluids and/or fluids to be aerosolized.
Turning now to
Also as illustrated by
The vibratory element 812 can be in mechanical communication with the support member 808. For instance, the vibratory element 812 can be mechanically coupled to the support member 808 through a variety of means. Merely by way of example, the vibratory element 812 can be bonded to the support member 808 with an adhesive 836. For instance, in some cases, the vibratory element 812 may be attached with mechanical fasteners to the support member 808. In other cases, the vibratory element 812 and the support member 808 may be integrally formed, perhaps from the same material. In certain embodiments, as shown in
In some cases, 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. As discussed above, one such bonding material may be an adhesive 844. Other bonding materials can include paints, epoxies, primers, and the like, as discussed herein. As illustrated by
Other embodiments can include one or more additional layers 868 of bonding material, which also can comprise any of the bonding materials discussed herein. The additional layers 868 can overlay the first layer 864 and can, additionally, be applied to portions of the support member 808. As illustrated more clearly by
In some embodiments, the sealing member 804 can comprise an elastomer, including any of those discussed above. In a particular embodiment, 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, Geschaftsbereich 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.
As noted above, in some embodiments, prior to molding the sealing member 804 about the aerosol generator, a layer of primer (which can be thought of as one of the layers 868 in
In other embodiments, a layer of epoxy (which can be thought of as the first layer 864 in
It will be appreciated that the thickness of any bonding material (whether paint, primer, epoxy or the like) can be relatively small compared to the size of the aerosol generator and sealing member. As such, 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.
The aerosolizing element 1016 may be an aperture plate constructed of a high strength and corrosion resistant material. As one example, the plate body may be constructed from a palladium nickel alloy (e.g., an alloy of about 80%, by wt., palladium and 20%, by wt. nickel). The element 1016 may also be made out of alloys comprising Ni—Cr—Mo, Ni—Cr—W, etc., which has a galvanic potential close to alloys of Pd—Ni. These materials are corrosion resistant to many corrosive materials particularly solutions with relatively low pH levels (e.g., pH of about 3.5 or less), such as medicament solutions for treating respiratory diseases by inhalation therapy, such as an albuterol sulfate and ipratroprium solution, which is used in many medical applications. Further, the palladium nickel alloy has a low modulus of elasticity and therefore a lower stress for a given oscillation amplitude. Other useful palladium nickel alloys are described generally in J. A. Abys, et al., “Annealing Behavior of Palladium-Nickel Alloy Electrodeposits,” Plating and Surface Finishing, August 1996, “PallaTech® Procedure for the Analysis of Additive IVS in PallaTech® Plating Solutions by HPLC” Technical Bulletin, Lucent Technologies, Oct. 1, 1996, and in U.S. Pat. No. 5,180,482, the complete disclosures of which are herein incorporated by reference. Materials in addition to Pd—Ni alloys that may be used to construct the aperture plate may also include other palladium alloys (e.g., Pd—Co alloys), and nickel alloys (e.g., Ni—Au alloys), gold, and gold alloys, as well as those described in U.S. Pat. No. 6,755,189, the entire contents of which are incorporated by this reference for all purposes.
The support member 1012 may be made or coated with a material that has a galvanic potential that is substantially equal to the galvanic potential of the aerosolizing element 1016. In some examples, the support member 1012 may be made from the same material as the aerosolizing element 1016, insuring the galvanic potentials for each component are equal. In other examples, the galvanic potentials are substantially equal enough so that the difference in the galvanic potentials is small than the difference between stainless steel and an alloy of 80% palladium and 20% nickel. In still other examples, the galvanic potentials are substantially equal enough to reduce the rate of galvanic corrosion of the material with lower galvanic potential below that observed when the support member 1012 is made of pure 316 stainless steel, and the aerosolizing element 1016 is made of a Pd—Ni alloy. Additional examples of materials that can be used in support member 1012 (as well as the aerosolizing element 1016) include alloys of nickel, chromium and other metals such as molybdenum and/or tungsten. For example, the alloy may include about 60% or more by weight of nickel and chromium, and/or about 80% or more by weight of nickel, chromium and molybdenum. Additional examples of the alloys include INCONEL® alloys from Haynes International of Kokomo, Ind., such as INCONEL® 625, which comprises an alloy of 21.5% by wt. Cr, 9% by wt. Mo, with the balance being Ni. Examples also include HASTELLOY® “C-Type” alloys from Haynes International of Kokomo, Ind., that have about 16-22% by wt. Cr, about 9-16% by wt. Mo, about 0-4% by wt. W, with the balance being Ni. HASTELLOY® C-276, for example includes about 16% by wt. chromium, about 16% by wt. molybdenum, about 4% by wt. tungsten, with the balance being nickel.
The support member 1012 and/or the aerosolizing element 1016 may also include alloys of cobalt, chromium, nickel, molybdenum and iron such as Conichrome®, Phynox™, and/or Elgiloy® produced by Fort Wayne Metals of Fort Wayne, Ind., among other alloys. In some formulations, Conichrome® may include about 40% by wt. cobalt, about 20% by wt. chromium, about 15% by weight nickel, about 7% by weight molybdenum; small amounts of carbon (e.g., about 0.06%), manganese (e.g., about 2%), silicon (e.g., about 0.5%), phosphorous (e.g., about 0.005%), sulfur (e.g., about 0.0015%), and beryllium (e.g., about 0.0002%); with the balance of the alloy including iron.
As noted above, achieving substantially equal galvanic potential between the support member 1012 and aerosolizing element 1016 may done by coating one or both components. For example, the support member 1012 may be machined from stainless steel and coated (e.g., electroplated, anodized, dipcoated, etc.) with a Pd—Ni alloy that is substantially equal to the galvanic potential of the aerosolizing element 1016.
Turning now to the molding process,
Hence, certain embodiments of the invention provide methods for creating aerosol generator assemblies. One exemplary embodiment 1900 is illustrated by
The method 1900 comprises providing a aerosol generator (block 1904), which can, in some embodiments, include any of the aerosol generators discussed herein. At block 1908, 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. At block 1912, 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. In other cases, the curing process can take place at a relatively high temperature, for a specified period of time. Optionally, 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.
At block 1920, 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. As noted above, 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).
Having described several embodiments, it will be recognized by those of skill in the art that various modifications, alternative constructions, and equivalents may be used without departing from the spirit of the invention. Additionally, a number of well known processes and elements have not been described in order to avoid unnecessarily obscuring the present invention. Accordingly, the above description should not be taken as limiting the scope of the invention.
Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included.
As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a process” includes a plurality of such processes and reference to “the electrode“includes reference to one or more electrodes and equivalents thereof known to those skilled in the art, and so forth.
Also, the words “comprise,” “comprising,” “include,” “including,” and “includes” when used in this specification and in the following claims are intended to specify the presence of stated features, integers, components, or steps, but they do not preclude the presence or addition of one or more other features, integers, components, steps, acts, or groups.
This application is related to U.S. patent application Ser. No. 11/097,488, filed Apr. 1, 2005, which is a continuation of U.S. Pat. No. 6,915,962, filed May 20, 2003, which claims priority to U.S. Provisional Pat. App. No. 60/382,256, filed May 20, 2002. This application is also related to U.S. patent application Ser. No. 09/822,573, filed Mar. 30, 2001, and U.S. Pat. No. 6,755,189, filed May 18, 1999, and issued Jun. 29, 2004. The entire disclosures of all the above listed applications are herein incorporated by reference for all purposes.
