The invention relates generally to devices and methods for spraying liquids and specifically to devices and methods that electrostaticly aerosolize liquids for spraying.
Devices and methods for forming fine sprays by particular electrostatic techniques are known. For example, U.S. Pat. No. 4,962,885 to Coffee, incorporated by reference herein, describes a process and apparatus to form a fine spray of electrostaticly charged droplets. More specifically, the process and apparatus comprise a conductive nozzle charged to a potential of the order of 1-20,000 volts, closely adjacent to a grounded electrode. A corresponding electric field produced between the nozzle and the grounded electrode is sufficiently intense to atomize liquid delivered to the nozzle, and thereby produce a supply of fine charged liquid droplets. However, the field is not so intense as to cause corona discharge, with resulting high current consumption. Advantageous uses of such liquid dispenser process and apparatus include sprayers for paint and/or spraying of crops. Aerosolization of liquids using electric fields is often referred to as electrostatic aerosolization of the liquid.
More recently, there has been a recognition that such spraying devices are extremely useful for producing and delivering aerosols of therapeutic products for inhalation by patients. In one particular example, described in U.S. Pat. No. 6,302,331 to Dvorsky et al. incorporated by reference herein, fluid is delivered to a nozzle that is maintained at high electric potential relative to a proximate electrode to cause aerosolization of the fluid with the fluid emerging from the nozzle in the form of, for example, a so-called Taylor cone. One type of nozzle used in such devices is a capillary tube that is capable of conducting electricity. An electric potential is placed on the capillary tube which charges the fluid contents such that as the fluid emerges from the tip or end of the capillary tube in a manner to form the Taylor cone.
The Taylor cone shape of the fluid before it is dispensed results from a balance of the forces of electric charge on the fluid and the fluid's own surface tension. Desirably, the charge on the fluid overcomes the surface tension and at the tip of the Taylor cone, a thin jet of fluid forms and subsequently and rapidly separates a short distance beyond the tip into an aerosol. Studies have shown that this aerosol (often described as a soft cloud) has a uniform droplet size and a high velocity leaving the tip but that it quickly decelerates to a very low velocity a short distance beyond the tip.
Electrostatic sprayers produce charged droplets at the tip of the nozzle. Depending on the use, these charged droplets can be partially or fully neutralized (with a reference or discharge electrode in the sprayer device) or not. The typical applications for an electrostatic sprayer, without means for discharging or means for partially discharging an aerosol would include a paint sprayer or insecticide sprayer. These types of sprayers may be preferred since the aerosol would have a residual electric charge as it leaves the sprayer so that the droplets would be attracted to and tightly adhere to the surface being coated. Under certain circumstances (i.e., delivery of some therapeutic aerosols), it may be preferred that the aerosol be completely electrically neutralized.
Moreover, electrostatic-type inhalers, in which the charge on the droplets is typically neutralized, have demonstrated advantages over more conventional metered dose inhalers (MDI) including producing more uniform droplets, enabling the patient to inhale the formed aerosol liquid or mist with normal aspiration, producing higher dosage efficiencies, and providing more reproducible doses.
It is often advantageous and/or important to consistently reproduce an aerosolized liquid having a particular physical characteristic, e.g., droplet size, size distribution, rate of aerosolization, or plume angle for maintaining a consistent therapeutic product dosage or for a stable applications of a liquid over crops or surfaces to be painted or other non-medicinal applications. However, variations in environmental factors, such as humidity, temperature, or barometric pressure due to climate variations, changes in altitude, or otherwise, or production variations in the dispenser configuration including nozzle geometry, often make it difficult to consistently and repeatedly produce the desired physical characteristic(s) in the aerosolized liquid. As a consequence, devices that can deliver consistent aerosol properties under extremes of operating conditions have not been available. Such devices had to be operated within limited humidity, temperature or altitude ranges in order to consistently produce the aerosolized liquid with the desired physical characteristics. In reality, changes in properties of the air between the electrodes can lead to inconsistent performance with respect to droplet production. In addition, costly rigid manufacturing variances and tolerances are required for manufacturing such devices. Small variations in nozzle geometry such as electrode positions have adverse consequences in the formation of aerosolized liquids consistently having desired characteristics. Accordingly, it is desirable to develop a method for aerosolizing a liquid that is highly robust and not influenced by changes in operating conditions such as environmental parameters or small changes in device geometry.
Thus, improved dispensing devices and methods are desired to overcome the requirements for rigid manufacturing tolerances and operation of electrostatic spraying devices within limited environmental ranges.
This invention is based on the discovery that it is possible to compensate for variations in operating conditions such as, for example, different humidity, temperature and barometric pressure, to maintain a desired characteristic of an aerosolized liquid by regulating an electrical characteristic such as, for example, voltage, used for generating the electric field which is used to produce the liquid droplets. The value of the particular electrical characteristic being regulated can be calculated from measurements made by an environmental sensor located in the proximity of the electrodes. In accordance with an alternative embodiment of the invention, it has been discovered that it is also possible to determine the value for the particular electrical characteristic being regulated based on a detected different electrical parameter such as, for example, current, in the circuit used to generate the desired electric field.
Thus, the invention is directed to methods and devices for generating an electric field proximate to an outlet of a liquid supplier to cause liquid issuing from the outlet to be aerosolized and regulating an electrical characteristic, e.g., voltage, for generating the electric field based on a detected parameter of the operating environment or circuit used to generate the electric field to compensate for differing operating conditions. The detected parameters may be an electrical characteristic of circuit generating the electrical field, e.g., current drawn, or measurements from environmental sensors.
In accordance with one embodiment of the invention, it is possible to compensate for adverse effects of changing relative humidity and other environmental conditions in the aerosolization process by regulating the voltage used for the electric field generation. In accordance with one example of such embodiment, the voltage is regulated to (1) provide a substantially constant voltage, such as, for example, in the range of 10 kV and 12 kV for generation of the electric field when the current drawn by such electric field generation is within a first range such as, for example, between 0 μA and 10 μA; and (2) provide a substantially constant power wherein the voltage is adjusted based on the current drawn to maintain such substantially constant power when the drawn current is greater than 10 μA. In such an example, the characteristic of droplet size formed in the aerosolized liquid is in a desired range such as, for example, between 0.1 and 6 microns despite such formation being subjected to a broader range of environmental conditions than is achievable with present electrostatic aerosolization liquid dispensers.
The present invention is also useable for aerosolizing different liquids having different electrical properties by determining, empirically or otherwise, the necessary electrical characteristic profile for voltage and current regulation required for maintaining a substantially constant characteristic of an aerosolized liquid over a broad range of operating conditions. In accordance with the present invention, a liquid dispenser effectively maintains a desired physical characteristic in the aerosolization of a liquid by compensating for a larger range of environmental conditions than present liquid dispensers including compensating for manufacturing variations that may occur in mass production of such dispensers.
Suitable applications of the invention include, for example, to spraying crops, applying paint or delivery of therapeutic liquids in an inhaler to a patient's lungs.
The accompanying drawings incorporated in and forming part of the specification illustrate several aspects of the invention, and together with the description serve to explain the principles of the invention. In the drawings:
The invention relates to methods and devices for electrostaticly aerosolizing liquid for the purpose of spraying. In particular, the invention provides the capability to repeatedly form such aerosolized liquids having a substantially consistent particular characteristic in a desired range despite being subjected to a variety of environmental conditions such as, for example, differences in humidity, temperature, barometric pressure or manufacturing variations in the sprayer configuration. Suitable applications of the invention include, for example, spraying crops, applying paint, or delivering liquids having therapeutic properties by way of an inhaler to a patient's lungs.
Although the following description primarily focuses on an exemplary pulmonary delivery device (inhaler) implementation of the invention, it should be readily understood that such teachings apply to sprayers in other applications. Other suitable applications of the invention include, for example, to spray crops, paint or to generally coat surface areas with other liquids. The description further teaches different aspects of the invention by electrohydrodynamic (EHD) aerosolization of the therapeutic fluid with the aerosolized fluid emerging from a nozzle in the form of a so-called Taylor cone.
Liquids suitable for aerosolization by EHD spraying generally are characterized by particular electrical and physical properties. For example, without limiting the scope of the invention, liquids having the following electrical and physical characteristics permit optimum performance by the device and method to generate a clinically relevant dose of respirable particles within a few seconds: (1) Liquid surface tension typically in the range of about 15-50 dynes/cm, preferably about 20-35 dynes/cm, and more preferably about 22-33 dynes/cm; (2) Liquid resistivity typically greater than about 200 ohm-meters, preferably greater than about 250 ohm-meters, and more preferably greater than about 400 ohm-meters (e.g., 1200 ohm-meters); (3) Relative electrical permittivity typically less than about 65, preferably less than about 45; and (4) Liquid viscosity typically less than about 100 centipoise, preferably less than about 50 centipoise (e.g., 1 centipoise). Although the above combination of characteristics allows optimum performance, it may be possible to effectively spray liquids with one or more characteristics outside these typical values using the device and method of the invention. For example, certain sprayer nozzle configurations or electrode placement may allow effective spraying of less resistive (more conductive) liquids.
Generally, therapeutic agents dissolved in ethanol are good candidates for EHD spraying because the ethanol base has a low surface tension and is nonconductive. Ethanol also is an antimicrobial agent, which reduces the growth of microbes within the drug formulation and on the housing surfaces. Other liquids and solvents for therapeutic agents also may be delivered using the device and method of the invention. The liquids may consist of drugs, or solutions or suspensions of drugs in compatible solvents.
As described above, the EHD apparatus aerosolizes the liquid by causing the liquid to flow over a region of high electric field strength, which imparts a net electric charge to the liquid. In the present invention, the region of high electric field strength sometimes is provided by a negatively charged electrode within the spray nozzle. The negative charge tends to remain on the surface of the liquid such that, as the liquid exits the nozzle, the repelling force of the surface charge balances against the surface tension of the liquid. The electrical force exerted on the liquid surface overcomes the surface tension, generating a thin jet of liquid. This jet breaks into droplets of more or less uniform size, which collectively form a cloud. In another embodiment, the electrode is grounded while the discharge electrode is positively charged (at, for example, twice the voltage), or the nozzle electrode can be positive. In any case, a strong electric field is required.
The device is configurable to produce aerosolized particles of respirable size. Preferably, such respirable droplets have a diameter of less than or equal to about 6 microns, and more preferably, in the range of about 1-5 microns, for deep lung administration. In formulations intended for deep-lung deposition, it is preferable that at least about 80% of the particles have a diameter of less than or equal to about 5 microns for effective deep lung administration of the therapeutic agent. The aerosolized droplets are substantially the same size and have near zero velocity as they exit the device.
The range of volumes to be delivered to the pulmonary system is dependent on the specific drug formulation. Typical volumes are in the range of 0.1-100 μL. Ideally, the dose should be delivered to the patient during a single inspiration, although delivery during two or more inspirations may be acceptable under particular conditions. To achieve this, the device generally must be capable of aerosolizing about 0.1-50 μL, and particularly about 10-50 μL, of liquid in about 1.5-2.0 seconds. Delivery efficiency is also a major consideration for the pulmonary delivery device so liquid deposition on the surfaces of the device itself should be minimal. Optimally, 70% or more of the aerosolized volume should be available to the user.
In the Drawings, like reference numerals represent like components throughout the figures.
A regulated power supply 70 is electrically coupled to the nozzle 30 and discharge electrodes 80 and 82. The discharge electrodes 80 and 82 are positioned proximate to the nozzle 30 to create a corresponding electric field such that liquid emanating from a tip 35 of the nozzle 30 is aerosolized for discharge from outlet 60. The electric field is created by the power supply 70 by producing a sufficient voltage potential ΔV between the electrodes 80 and 82 relative to the nozzle 30. Exemplary ranges for the voltage potential ΔV are 8 KV to 20 KV, more preferably between 8 KV to 12 KV and most preferably 11 KV.
The liquid 50 to be aerosolized is held in the containment vessel 20 that stores and maintains the integrity of the therapeutic liquid. The containment vessel 20 may take the form of a holder for a drug enclosed in single dose units, a plurality of sealed chambers each holding a single dose of the drug, or a vial for enclosing a bulk supply of the drug to be aerosolized. Bulk dosing generally is preferred for economic reasons except for liquids that lack stability in air, such as protein-based therapeutic agents. The containment vessel 20 preferably is physically and chemically compatible with the therapeutic liquid including both solutions and suspensions and is liquid and airtight. The containment vessel 20 may be treated to give it antimicrobial properties to preserve the purity of the liquid contained in the containment vessel 20. Suitable containment vessels are further described in, for example, U.S. patent application Ser. No. 0/187,477, which is incorporated by reference herein.
The pump and valve mechanism 40 provides a desired amount of the liquid from the vessel 20 to the nozzle 30 at a desired pressure or volumetric flow rate. However, the specific configuration chosen for the pump and valve mechanism 40 to perform such function is not critical to practicing the invention. Suitable configurations for the pump and valve mechanism 40 are described in U.S. Pat. Nos. 6,368,079 and 6,827,559, which are incorporated by reference herein. Additional pump configurations for the pump 40 are also disclosed in U.S. Pat. No. 4,634,057, which is likewise incorporated by reference herein. The containment vessel 20 alone, or in combination with the pump and valve mechanism 40, provide a liquid supplier for aerosolization of liquids maintained by the containment vessel 20.
Suitable nozzle configurations for the nozzle 30 include, for example, those nozzle configurations described in U.S. Pat. Nos. 6,397,838, and 6,302,331 and U.S. patent application Publication No. 2004/0195403 which are incorporated by reference herein.
In the depicted embodiment of the invention in
One exemplary circuit 200 usable for the power supply 70 of
Referring again to
In operation, for example, the controller 260 causes the current regulation circuit 280 to operate in a first or second mode based on the magnitude of the received feedback signals IF and VF. In the first mode, alternatively referred to as the voltage control mode, the controller 260 generates control signal C1 with a value to cause the current regulation circuit 280 to pass voltage VR generated by the voltage regulation circuit 210 directly to the switching circuit 220 with little or no attenuation. In the second mode, alternatively referred to as the current control mode, the controller 260 generates the control signal C1, with a value to cause current regulation. In this mode, the current regulator circuit 280 passes voltage VR generated by the voltage regulation circuit 210 through impedance Z to the switching circuit 220, i.e., providing a corresponding reduced voltage to the switching circuit relative to the voltage provided when the current regulator 280 is operated in its first mode.
Suitable values for changes in VR in this mode relative to the first mode are, for example, typically from between 0% and approximately 25% reduction in the voltage VR. The particular change in VR selected for this mode will be based upon, for example, nozzle geometry, formulation characteristics, and environmental conditions. During operation, the controller 260 monitors the feedback current signal IF. If the signal IF possesses a magnitude below a threshold value, then the control signal C1 is produced to cause the switching circuit 220 to operate in its voltage control mode. If the monitored feedback current signal IF reaches or exceeds the threshold value, then the control signal C1, is generated to cause the switching circuit 220 to operate in its current regulated mode with an increased attenuation of the signal VR based on a transfer function of the controller 260. The transfer function may be determined by empirical data. Suitable transfer functions useable with the invention include, for example, constant current, constant power, or a non-linear response or some combination thereof.
It is possible to refer to the first mode of operation as a constant voltage mode assuming that the voltage regulation circuit 210 provides a voltage to the current regulation circuit 280, and subsequently the switch circuit 220 and correspondingly the transformer 230 of substantially constant magnitude. In another embodiment, it is also possible to refer to the second mode of operation in which the current regulation circuit 280 is limiting the voltage signal VR as a substantially constant power mode as the power provided to the transformer 230 would be substantially constant, i.e., VR2/Z, if the voltage regulation circuit 210 provides a substantially constant voltage to the switch circuit 220. In other embodiments, there may be multiple operating modes or a single operating mode where the control signal C1, is generated to adjust or regulate the voltage signal VR
The switching circuit 220 provides a desired modified voltage signal based on voltage signal VR. In some instances, the modified signal is similar to a square wave. The switching circuit 220 provides an “on-off” type signal to the transformer 230 in such a manner that the “time-average” of the on and off is equivalent to the voltage signal VR, and the voltage signal VR is correlated directly to the high voltage output VO as controlled by the controller 260 and the current regulation circuit 280. It is desirable for the current regulation circuit 280 to minimize fluctuations of any given voltage so that VR (and ultimately VO) remain within a given tolerance range.
In the embodiment illustrated in
In
In operation, the exemplary power supply circuit 200 of
Accordingly, in the previously described exemplary embodiment in
The operation of the power supply circuit 200 of
Thus, the magnitude of the output voltage Vo is critical to EHD performance. If the output voltage Vo is below a threshold limit, then aerosolization will not occur. However, if the output voltage Vo is above the threshold limit, but not high enough, the resulting droplets will be too big. Likewise, if the output voltage Vo is too high above the threshold limit, then the droplets produced will also be too big. In other voltage regions, the droplets may be too small.
An exemplary method for determining a suitable voltage-current function curve useable for aerosolizing liquid by way of an electric field having a physical characteristic maintained in a desired range over varying operating conditions is to experimentally determine such function by testing and monitoring the physical properties during aerosolization of a liquid with different voltages, currents and frequencies over a varying range of the operating conditions. Once a suitable voltage-current (and/or frequency) function curve has been determined then a corresponding regulated power supply can be configured to approximate or accurately produce the determined voltage-current function for generating the electric field.
Referring again to
Feedback voltage and current signals VF and IF produced by the high voltage stages circuit 240 are provided to the voltage regulation circuit 210 and the controller 260, respectively, with an indication of the corresponding values of the output voltage and current VO and IO. The drawn output current IO is dependent upon the effective impedance of the issuing liquid in combination with environmental conditions such as, for example, relative humidity, temperature, proximate distances between electrodes, the volume of fluid passing through the electric field, which may also be effected by variations in the nozzle tip diameter. If the controller 260 detects that drawn output current IO is larger than current I1 as depicted in
As was previously stated, such reduction of voltage VO in view of elevated output current IO has the effect of maintaining a physical characteristic of the aerosolized liquid such as, for example, droplet size to be consistently within the range of, for example, 0.1 to 6 microns for therapeutic liquids. In exemplary embodiments of the invention it is advantageous for IO to vary in a range by ±3 to ±4 μA.
Although
It is further possible to employ the optional environmental sensor 270 to better anticipate the desired output voltage VO. The exemplary power supply configuration 200 was depicted in
The circuitry for performing this third mode of operation should provide a sufficient non-linear response so as to cause output voltage VO to track the voltage-current function curve 420 depicted in
The design and configuration of the exemplary power supply circuit 200 of
The power supply circuit 500 in
In operation of the power supply circuit 500 of
The configuration of the depicted power supply circuits 200 and 500 in
The embodiments of the invention previously described with regard to
It should be understood that, although liquid spray embodiments of the invention are shown and described herein with regard to an inhalation device, embodiments of the invention are suitable for use in spraying crops, paint or for liquids intended to cover a surface. For instance, the invention has been described as a single voltage EHD device, i.e., with one or more electrodes, such as the nozzle electrode maintained at ground while other electrodes are charged to the desired voltage, for ease of discussion purposes only. The invention is also applicable to EHD devices that employ electrodes charged to two or more different voltages. In such instances, it is possible to employ two or more corresponding control circuits in accordance with the invention. It will be apparent to those skilled in the art that many other changes and substitutions can be made to the power supply circuit configuration or electric field generator described herein without departing from the spirit and scope of the invention as defined by the appended claims and their full scope of equivalents.
This application claims priority from U.S. Provisional Application No. 60/699,932 filed on Jul. 15, 2005. The above mentioned application is incorporated herein by reference.
Number | Date | Country | |
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60699932 | Jul 2005 | US |