Patent Grant
6837401
The present invention relates to apparatus and methods for delivery of topical anesthetics and refrigerants, hereinafter collectively referred to as vapocoolants. More particularly, the apparatus comprises containers, associated valve arrangements and, optionally, filters that provide a long shelf life and maintain delivery characteristics over the shelf life in a manner suitable for pharmaceutical applications. The apparatus operates over a range of pressure commonly encountered in medical applications to provide substantially uniform delivery of vapocoolant. The apparatus may be constructed to provide either a stream or a mist delivery.
Preferred vapocoolants include ethyl chloride, ethyl chloride-fluorocarbon blends, fluorocarbon fluids and blends of fluorocarbon fluids such as 15% dichlorodifluoromethane and 85% trichloromono-fluoromethane. Also, non-halogen containing low boiling fluids suitable for topical skin application may be used. The vapocoolant will typically operate as a self-propellant by providing a suitable pressure for discharge in a vapor space above the liquid supply of vapocoolant. However, an inert gas such as nitrogen may be combined with the vapocoolant to achieve modified discharge characteristics. For convenience, the invention is described hereinafter with particular reference to ethyl chloride.
Ideally, the containers and associated valve arrangements for ethyl chloride should have a shelf life of three years and meet United States Pharmacopoeia (“USP”) specifications as well as standard aerosol requirements for functionality. As discussed more fully below, certain medical applications also require unique jet stream characteristics over the life of the product. The USP specification for residue in ethyl chloride is 100 ppm.
Heretofore, valve-actuated spray bottles and so-called metal tube containers have been used for delivery of stream and mist flows of vapocoolant. Although such apparatus have provided effective delivery, they have not been entirely satisfactory. More particularly, it has not been possible to economically modify the prior art apparatus to comply with current FDA regulations and commercial production standards. Most notably, undesirable rates of product lost due to valve leakage have been experienced in connection with bottle apparatus. Although the metal tube apparatus provides substantially satisfactory performance, the cost of this delivery system including its threaded valve actuator is not economically attractive.
A current metal can spray system having a button actuated valve has not complied with contaminant or residue standards. That is, the vapocoolant within the spray can contains dissolved or dispersed contaminants believed to result from the solvent action of the vapocoolant on internal polymeric components of the spray can.
The vapocoolants may be used in topical application procedures requiring precise control of the area of skin contacted by the applied stream. For example, treatment of certain myofascial pain syndromes with vapocoolant in combination with stretching procedures may inactivate a trigger point and relieve the patient's pain. A discussion of myofascial pain and myofascial trigger points is provided in the International Rehabilitation Medicine Association monograph, Myofascial Pain Syndrome Due to Trigger Points, by David G. Simons M. D., November 1987, incorporated herein by reference. One specific myofascial therapy is the stretch and spray method of treatment which permits gradual passive stretch of the muscle and inactivation of the trigger point mechanism. To that end, a jet stream of vapocoolant is applied to the skin in one-directional parallel sweeps. Initially, one or two sweeps of spray precede stretch to inhibit the pain and stretch reflexes. The spray of vapocoolant is applied slowly over the entire length of the muscle in the direction of and including the referred pain zone. As described, the stream flow and size characteristics together with precise positioning of the vapocoolant along the muscle being treated is important to achieve inactivation of the trigger point mechanism.
In such procedures, a stream delivery of relatively small dimension is preferred. For example, the diameter of the stream at the valve nozzle may be in the range of several thousandths of an inch, e.g., from about 0.004″ to about 0.015″. Preferably, the delivery flow is stable and the stream configuration is sufficiently maintained to achieve the desired skin contact area with the valve nozzle being positioned up to about 10 or 15 inches from the patient.
In order to achieve such stream stability, the fluid delivery components of the container must not be affected excessively by changes in pressure that occur with change of container orientation during stream application and reduction of the vapocoolant supply within the container during the application life of the container, i.e. the time period within which the container is periodically used before emptied of vapocoolant. Similarly, the button valve itself must receive the flow of vapocoolant from the supply thereof within the container and establish satisfactory fluid flow characteristics prior to the exit of the fluid from the nozzle opening.
The achievement of a fine jet stream requires a nozzle having a highly uniform orifice or opening that is free of dimensional irregularities. For example, a nozzle opening having a diameter of about 0.005″ preferably has a size tolerance of ±0.0005″ along a length in the order of 0.02″.
The reliable provision of such jet stream flows has heretofore been inhibited by the presence of contaminants which may result from in situ formed solid residues or derived from the spray apparatus including the container, valve, actuator and/or flow passage surfaces contacted by the vapocoolant. Such contaminants may partially block or otherwise sufficiently inhibit or alter flow through the nozzle discharge bore and/or opening so as to prevent the achievement of the desired jet stream. Such contaminants may result from plastic dip tubes and actuator elements that retain manufacturing debris of extremely small size, e.g., elongated flash debris having a 0.0005″ diameter and a 0.010″ length. Cleaning techniques including washing and vacuum removal are economically undesirable and often not sufficiently reliable.
It has now been found that effective and economical container apparatus and methods may be provided for delivery of stream and mist flows of vapocoolant through the judicious selection of polymeric components in accordance with the specific vapocoolant and the operating characteristics of the valve apparatus within the container.
It had also been found that fine jet stream flows of vapocoolant may be reliably provided with filtering of the vapocoolant. The vapocoolant is filtered within the container apparatus by a filter sized to remove debris of a size typically associated with the manufacture of the dispensing apparatus components.
Further, the container apparatus may include button-type actuators designed to cooperate with the coacting valve apparatus within the container to yield stable sealing resulting in long-term shelf life, e.g., in the order of two years. Similarly, uniform delivery and flow characteristics are achieved as the contents of the container are used during the application-life of the container.
The valve arrangement includes a sealing surface of fluoroelastomer that has been found to provide chemical and physical stability in respect to vapocoolants in combination with resiliency characteristics necessary to long-term fluid tight sealing engagement. Surprisingly, this has been achieved in connection with button type actuators which are characterized by relatively low valve actuation forces of 4 to 9 lbs. as contrasted with the threaded valve actuators of the prior art. Moreover, this has been achieved in the harsh chemical environment of an ethyl chloride system. As noted above, such was not heretofore possible without the use of an economically unattractive threaded valve arrangement for dispensing the vapocoolant.
Accordingly, the fluoroelastomer compositions may be selected to afford the necessary inertness and sealing resiliency properties to enable an economical vapocoolant delivery container having an acceptable shelf life. Useful fluoroelastomer compositions are characterized by the following properties.
1. A durometer shore A value of 50 to 100 and more preferably 80 to 90, as measured by ASTM D2240;
2. Low permeability measured as product loss from assembled can through valve assembly in the range of less than about 3.0 g/year and preferably from about 1.0 to 2.0 g/year or less;
3. Chemical inertness in respect to ethyl chloride as characterized by gas chromatography characterization of impurities equal to less than 100 ppm;
4. A dimensional stability that exhibits limited dimensional change as required by valve design and, for example, about ±5%;
5. Low solid residue in ethyl chloride as characterized by ethyl chloride USP non-volatile residue test, the non-volatile residue less than 200 ppm.
Using the foregoing guidelines, a suitable gasket for a valve arrangement in an ethyl chloride system was formed using a commercially available fluoroelastomer sold under the DuPont trademark Kalrez 6185. Kalrez is a perfluoroelastomer that is a copolymer of tetrafluoroethylene and perfluoromethyl vinyl ether with small amounts of a perfluorinated comonomer to provide chemical cross linking sites.
In the foregoing application, a button actuated valve was fitted to a metal container or can. It is estimated that the valve spring developed a valve closing force of less than 5 lbs. A shelf life of about two years was achieved with little or no loss of the ethyl chloride from the metal can. Similarly, minimal contamination from solid residue occurred. Solid residue was raised by about 70 ppm over the raw material.
Similar resins include Kalrez 6221 or 6230 which are also perfluoroelastomer. Additional useful resins are sold by DuPont under the trademark Zalak.
Other polymeric components within the container should also be selected with regard to the properties of the vapocoolant. In the case of ethyl chloride, it has been found that the dip tube may be formed of a fluorocarbon resin such as polytetrafluoroethylene.
The container may comprise an aluminum or steel can. Presently, it is preferred to use polymeric liners for the can interiors of aluminum. In the case of aluminum, a liner of polyamide/imide resin may be used, but an unlined container is preferred. In the case of steel, a liner of epoxy/phenolic resin may be used. These resins are known in the art and they are commercially available.
In accordance with the foregoing guidelines, one skilled in the art may select useful fluoroelastomers by trial and error to provide a valve arrangement and container for a particular vapocoolant.
For purposes of achieving a fine jet stream of suitable dimension and sufficient integrity to enable the precision application of the vapocoolant required in certain myofascial treatments, suitable nozzle discharge bore sizes and lengths have been identified. Moreover, it has been found that such nozzles are conveniently formed of metallic materials in order to better maintain dimensional tolerances and geometric configurations.
The reliability of the container apparatus to provide such fine jet stream flows has been enhanced by filtering of the vapocoolant. More particularly, the container apparatus is provided with an in situ filter located in the flow path of the vapocoolant stream. Preferably, the filter is positioned immediately upstream of the nozzle discharge bore.
Referring to
The interior surfaces of the container 10 may be provided with a protective polymeric coating or film 22. As noted above, a polyamide/polyimide (PAM) resin may be used on aluminum, and an epoxy/phenolic resin may be used on steel, but an unlined container is preferred.
The container 10 is sized to hold about 3.5 ounces of vapocoolant. However, containers may be sized to hold from about 1 ounce to about 10 ounces. The cross-sectional area of the container is selected to assure development of a vapor pressure sufficient to discharge the contents of the container.
The valve apparatus 12 includes a valve body 24 having a coil spring 26 mounted therein. Spring 26 is arranged to resiliently bias a spring cup 28 into sealing engagement with a gasket 30.
The valve body 24 and spring cup 28 may be formed of a resin material that is resistant to the ethyl chloride environment. For example, the body 24 and cup 28 may be formed of a polyamide resin such as nylon.
The spring 26 is formed of stainless steel and has a spring force sufficient to maintain a fluid tight seal between the cup 28 and gasket 30. Suitable springs have been formed of stainless steel wire having a diameter of 0.027″. The spring is arranged in a coil configuration having an axial length of about 0.45″ and a diameter of about 0.2″. Satisfactory performance may be obtained with valve actuation forces ranging from 3 to 15 lbs. and more preferably, from about 5.5 lbs. to about 8 lbs.
The gasket 30 has an annular shape. It is formed by extrusion of the perfluoroelastomer sold under the trademark Kalrez 6185. More particularly, the elastomer is extruded in a tubular form with an outside diameter of about 0.375″ and an inside diameter of about 0.139″. The extrusion is transversely sliced to form the gasket 30 with a thickness of from about 0.035″ to about 0.060″, and more preferably, 0.042″. These gasket dimensions have been found to provide suitable sealing with an annular engaging lip 28a provided by the spring cup 28 under the bias of the spring 26.
It should be appreciated that the upper mounting cup 16 is shown prior to clinching or crimping engagement with the valve apparatus 12. During clinching, the central hub of the cup 16 is radially compressed or clinched to firmly engage the upper annular portion of the valve body 24. The clinching process reduces the inside diameter of the gasket 30. An acceptable inside diameter range has been found to be from about 0.115″ to about 0.125″.
Referring to
The body portion 33 of the actuator 32 is formed of a polyamide resin such as nylon. A suitable nylon resin is sold by DuPont under the trademark Zytel.
The actuator 32 is arranged to be mounted to the central hub, or more particularly, the lip 16a of the cup 16 to permit limited axial movement towards the container 10. Accordingly, the actuator 32 may be moved downward towards the container 10 to cause the operating leg 36 to move the spring cup 28 axially into the valve body 24 against the bias of the spring 26. In this manner, the engaging lip 28a of the spring cup is moved out of sealing engagement with lower surface 30a of the gasket 30.
When the valve is opened by operation of the actuator 32 to move the lip 28a away from the surface 30a, vapocoolant rises through the dip tube 14 and passes through the valve body 24 into a slot 36a formed in the leg 36. The vapocoolant then passes into a first bore 38 extending through the leg 36 and communicating with a second bore 40 disposed in an upper region of the actuator 32. The second bore 40 extends to a nozzle insert 42 having a tapered discharge bore 44. The nozzle insert 42 is press-fitted into a nozzle mounting bore 46.
The nozzle insert includes a cylindrical portion having a diameter of about 0.2″ and an axial length of about 0.2″. A tip extends about 0.1″ from the spray end of the cylindrical portion. Accordingly, the total axial length of the nozzle insert is about 0.3″. The nozzle insert is formed of a suitably inert resin, such as an acetyl resin sold under the trademark Celcon M70.
The discharge bore 44 is provided with a smooth surface and a relatively shallow angle of inclination equal to about 15° from the center line to the adjacent interior surface so as to provide a cone angle of about 30°. The bore 44 includes a cylindrical portion 44a that has an inside diameter of 0.090″ and a length of 0.060″. The portion 44a extends to a cone portion 44b that is symmetrical about its longitudinal axis and terminates at a front surface 48 having a diameter “A” (
The nozzle insert 42 has been found to be securely fixed within the bore 46 by friction without measurable distortion of the stream emitted through the nozzle opening 50. That is, a stream having a diameter of about 0.008″ is emitted and the stream configuration is maintained at application distances ranging up to about 20 inches.
Referring to
The mounting of the actuator 52 to the container 10 and its operation of the valve apparatus 12 is similar to that described above with respect to the actuator 32. Accordingly, this discussion is not repeated.
The delivery of a mist spray is achieved with a discharge bore 60 formed in the body portion 54 of the actuator 52. The discharge bore 60 has a substantially cylindrical configuration and receives a mist spray insert 61 that terminates at a nozzle opening 62. The circular cross section of the discharge bore 60 and nozzle opening 62 may range in diameter from 0.010″ to 0.030″, and more preferably, 0.015″.
The mist spray emitted from the nozzle opening 62 compresses a dispersed flow of vapocoolant. The cone shape may be of about a 45° angle. A vapocoolant flow rate of about 0.3 grams/second is typical.
It should be appreciated that the dip tube 14 may be omitted to limit the container 10 to inverted-type use. Of course, internal valve apparatus may also be used to enable container operation in substantially any orientation.
Referring to
Referring to
The mounting of the actuator 80 to the container 10 and its operation of the valve apparatus 12 is similar to that described above with respect to the actuator 32. Accordingly, the annular leg 86 includes a first bore 88 communicating with a second bore 90 that terminates at a nozzle mounting bore 92. A nozzle 94 having a nozzle orifice or opening 96 is mounted with an interference fit in the bore 92. The valve apparatus 12 and annular leg 86 cooperate with the bores 88 and 90 to provide a passageway to convey liquid vapocoolant from the supply thereof in the container 10 to the nozzle 94 for discharge through the nozzle opening 96.
The nozzle 94 may be provided with various exterior configurations as required in a particular actuator structure. The nozzle 94 is preferably formed of a metallic material such as brass or stainless-steel. The use of such a metallic material facilitates the provision of the nozzle opening 96 with dimensions sufficiently small to provide the desired jet stream. For example, electrical discharge machining (EDM) may be used to form the opening 96 with uniform dimensions and surfaces substantially free of irregularities in the nature of burrs or other shaping defects. Of course, the opening 96 may be formed by other manufacturing techniques such as drilling or laser cutting.
The nozzle orifice or opening 96 may range in diameter size from 0.004″ to 0.015″ with a tolerance of about 0.0005″ and a length of about 0.02″. A smaller diameter size tends to overly limit the flow of vapocoolant so that the cooling therapeutic effect is not obtained upon impingement of the stream on the skin. Increasing pressures do not provide sufficient increases in flow and/or tend to cause splash back at relatively high pressures, e.g., 60 psi, which tends to inhibit the desired skin cooling effects. On the other hand, diameter sizes greater than about 0.015″ tend to result in liquid vapocoolant flows that are too high and are not easily limited to the desired contact width to treat specific muscles. If the pressure is excessively decreased, e.g., to values less than about 4 psi, the required jet stream is not achieved.
In preferred applications, a fine jet stream may be achieved with a nozzle opening diameter size in the range of from about 0.005″ to about 0.007″. At a pressure of about 5 psi, such a jet stream will expand to a diameter of about 0.010″, and no more than about 0.015″, after traveling about 4″ from the nozzle opening.
A slightly larger medium jet stream may be achieved with a nozzle opening diameter size in the range of from about 0.007″ to about 0.009″.
Referring to
As previously discussed, the contaminants primarily comprise manufacturing debris associated with the dip tube, valve and actuator as well as the container. The filter may be sized to accommodate expected levels of contaminants without impeding the flow of the vapocoolant so as to prevent formation of the desired jet stream.
Referring to
Referring to
In this embodiment, a filter 128 comprises a non-shedding napkin or paper material. A suitable paper filter material is KIMTEX P/N 33560 40 sold by Kimberly Clark. As illustrated, a small portion of the paper filter material weighing less than a gram is fitted into the bore 118 to block the entrance to the bore 120. In this manner, the liquid vapocoolant is filtered prior to being discharged through the nozzle 124.
In addition to metal and paper type filters, polymeric membranes of suitable porosity may be used as filters. A variety of suitable membranes are sold by the Whatman Group including a cellulose filter media having a separation size of 40 microns. Gelman, through Paul Life Sciences, also distributes a suitable cotton linter paper having a separation size of 30 microns.
While the invention has been shown and described with respect to particular embodiments thereof, this is for the purpose of illustration rather than limitation, and other variations and modifications of the specific embodiments herein shown and described will be apparent to those skilled in the art all within the intended spirit and scope of the invention. Accordingly, the patent is not to be limited in scope and effect to the specific embodiments herein shown and described nor in any other way that is inconsistent with the extent to which the progress in the art has been advanced by the invention.
This application claims the priority of provisional application Ser. No. 60/234,488, filed Sep. 22, 2000.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCTUS01/29627 | 9/21/2001 | WO | 00 | 1/31/2003 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO0224548 | 3/28/2002 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 4035303 | Ufferfilge | Jul 1977 | A |
| 4141472 | Spitzer et al. | Feb 1979 | A |
| 5273191 | Meshberg | Dec 1993 | A |
| 5988449 | Fuchs et al. | Nov 1999 | A |
| Number | Date | Country | |
|---|---|---|---|
| 20040040978 A1 | Mar 2004 | US |
| Number | Date | Country | |
|---|---|---|---|
| 60234488 | Sep 2000 | US |
