|Número de publicación||US3163166 A|
|Tipo de publicación||Concesión|
|Fecha de publicación||29 Dic 1964|
|Fecha de presentación||28 Abr 1961|
|Fecha de prioridad||28 Abr 1961|
|Número de publicación||US 3163166 A, US 3163166A, US-A-3163166, US3163166 A, US3163166A|
|Inventores||Migliarese Joseph Francis, Brant Joseph Henry|
|Cesionario original||Colgate Palmolive Co|
|Exportar cita||BiBTeX, EndNote, RefMan|
|Citas de patentes (9), Citada por (140), Clasificaciones (16)|
|Enlaces externos: USPTO, Cesión de USPTO, Espacenet|
Dec. 29, 1964 J. H. BRANT ETAL IoNToPHoREsIs APPARATUS Filed April 28, 1951 INVENToRs JOSEPH H. ERAN? '.gaEP/f F: MIGL//IRFSE United States Patent O 3,163,166 IONTOPHRESHS APPARATUS Joseph Henry Brant, Summit, and Joseph Francis Migliarese, Bound Brook, NJ., assignors to Colgate- Palmolive Company, New York, N.Y., a corporation of Delaware Filed Apr. 28, 1961, Ser. No. 106,294 6 Claims. (Cl. 12S-405) The present invention relates to ion therapy of the soft tissue of the body, ie., the skin and mucous membranes. More particularly, it relates to an improved apparatus particularly adapted for use in this process.
VIn accordance wit-h the present invention there is provided a method for the treatment by iontophoresis of a selected area of soft tissue surface which method comprises passing an electric current between a selected area of soft tissue surface and an external electrode. The current is passed through electrolyte interposed and maintained between the external electrode and the area of soft tissue surface while keeping said electrode in motion over said area. Preferably the electrolyte comprises a thickened aqueous solution of an ionized medicament.
Also in accordance with the present invention is a hand-held iontophoresis apparatus especially adapted to carry out the instant process, said apparatus comprising a casing, a uid reservoir within said casing, an opening in said casing, and a spherical electrode mounted in said opening and protruding out of said casing, said spherical electrode being free to rotate and being in communication with said uid reservoir.
It has been found that in carrying out the process of the present invention, the application of electric current from a moving electrode which is covered on its surface by a film of liquid electrolyte is highly effective in that it facilitates the establishment and maintenance of a continuous film of electrolyte between the electrode surface and the skin. By providing for continuous replenishment of the film of electrolyte on the contact surface of the moving electrode, a cosaction is achieved which overcomes numerous undesirable disadvantages involved in previously proposed iontophoresis systems. Thus the instant invention is particularly advantageous with respect to avoiding electrode burns for the reason that in non-abraded skin, electrode burns originate at the site of an epidermal orifice (hair follicle or sweat duct opening) where llocalized increases in the concentration of the electrolyte often become established. Such localized increases create a focus of minimum electrical impedance and a maximum current flow and epidermal destruction. Such localized concentrations of current iiow and resultant burning are avoided by the present invention.
In order better to illustrate the instant invention, reference is made to the accompanying drawings in which:
FIG. 1 is .an elevation, principally in section, of a preferred iontophoresis apparatus in accordance with the invention and having therein a self-contained power unit; and
FIG. 2 illustrates in detail a schematic circuit of an appropriate power unit for use in the apparatus of FIG. 1.
The iontophoresis .apparatus of FIG. l comprises an outer casing in the form of a cylinder closed at one end and tapered at the other, said casing being indicated generally by the reference character 10.
The outer casing 10 includes an electrically conductive, e.g. metal, central cylindrical body 12 one end of which terminates in a transverse non-conductive end wall 14. A pair of metal prongs 16 adapted for insertion into a conventional 117 volt A.C. outlet protrude from the end wall 14. Normally these prongs are covered by an insulating screw cap 20 which is removably aixed to the conductive cylinder 12 by mating threads.
On its other end, the cylindrical body 12 carries a raised ridge 22 on its outer surface and a female thread 24 on its inner surface. A slip-on cap 26 having, on its inner surface, an annular recess which engages the ridge 22, is provided as a protective cover for the tapered end of the appar-atus when the device is not in use. Secured to the female thread 24 by a mating male thread is a non-con ductive head piece 30 having a frusto-conical extremity in which a non-deformable spherical metal electrode 32 is retained in a manner such that it is free to roll in any direction.
An electrically insulated partition wall 34 divides the casing 10 into two principal compartments, a iirst or electriolyte compartment which is principally associated with the interior of the head piece 3th land a second or power unit compartment which constitutes the interior section between the partition wall 34 and the transverse non-conductive end wall 14.
Located in the electrolyte compartment within the head piece 30 is a replaceable fluid-containing cartridge 36. The cartridge constitutes a liquid electrolyte-retaining vessel constructed and disposed such that liquid therein is supplied therefrom to the surface of the spherical electrode 32. The cartridge is closed at one end and tapers at its other end to conform to the shape of the interior of the head piece 30. A gasket 40 provides a liquid tight seal between the head piece and the cartridge. Liquid is supplied from the cartridge 36 to the rigid spherical electrode 32 through a .mouth in the tapered end of the cartridge by transmittal through an electrically conductive porous septum 42.
A double pole triple throw switch 44 is mounted on the cylindrical body 12 at a point convenient for operation by the lingers when the apparatus is held in the hand. As
will be described in further detail below, this switch is wired in associaton with the prongs 16 and a rechargeable self-contained power unit 46 such that operation of the switch provides for (1) supplying electric power for use of the apparatus in ion therapy in the On position; (2) recharging of a storage cell contained within the power unit in the Charge position; and (3) switching the apparatus to an Off condition.
The output of the power unit 46l is supplied via conduit S0 to the conductive cylindrical body 12, thus forming an electrode of this conductive body 12 which contacts the palm of the hand of the user.
The output of the power unit is also coupled through a second conduit 52 to a rivet 54 which pins a convex resilient metal leaf spring 56 at lone end thereof to a supporting insulator 6). The center of the leaf spring is contacted and depressed by -a metal pin 62 aflixed to and projecting axially outwardly from the sealed end or base of the replaceable electrolyte-containing cartridge 36. A rnetal conduit 64 `serves to connect the pin 62 to the conductive septum 42, thus providing an electrical continuity in the event that the level of the electrolyte fluid in the cartridge diminishes to such an extent that the fluid fails to act effectively 'as an electrical conduit between the pin 62 and the septum42. Electrical contact to the spherical electrode 32 is established by physical contact thereof with the septum 42 and with the electrolyte fluid issuing therefrom.
The power unit 46 illustrated in FIG. 2 includes a rechargeable l4.4 volt nickel-cadmium battery 68 which may be associated, by means of the switch 44, with a re- 'l charging circuit constituting a solid state diode rectifier 70 and a 5100 ohm resistor 71 wired in series with the prongs 16. l
In its Off position, the switch 44 isolates the battery 68 electrically from the remainder of the apparatus.
In its n position, the switch 44 conducts power from the battery 68 to a circuit in which resistors 72, 73, 74,
75, 76 and 77 of 100,000, 1,800, 6,800, 300, 200, and 6,800 ohms resistance respectively are combined with two 2N44 transistors 82 and S4 and a 0.1 microfarad capacitor 86 to form a free-running transistorized multivibrator type of pulse generator. This type of circuit is well known and the choice of the components employed therein is not critical. The circuit illustrated provides a pulsating D.C. output having an amplitude of approximately 13 volts, a repetition rate of approximately 1,000 cycles per second, and a pulse width of approximately 680 microseconds.
In use for iontophoretic applications, the slip-on cap 20 is removed and the apparatus, with an electrolytecontaining cartridge 36 in place, is held in the hand of the subject to be treated, thus constituting the central cylindrical body 12 as an indifferent electrode in contact with that hand. The subject then throws the switch 44 to the On position, and uses the projecting spherical electrode 32 to massage the surface of that area of his body which he Wishes to treat. During use, the spherical electrode rotates and, of course, thereby supplies electrolyte from the reservoir in the cartridge 36 to the working surface or outwardly projecting electrolyte-covered portion of the electrode which impinges upon the surface of the area of tissue being treated. It is not necessary, however, for there to be constant supply of electrolyte from the reservoir to the electrode; periodic supply is adequate inasmuch as the electrode carries on its entire surface area an adequate supply of electrolyte for an extended treatment.
lt will be appreciated that the continuous maintenance of an electrolyte film over the Working surface of the active electrode is highly advantageous in that as long as the subject continues to move the electrode over the area Vto be treated, the film of electrolyte prevents localized current concentrations such as might occur at sweat ducts in instances where a stationary or electrolyte-depleted electrode is used.
It will also be appreciated, of course, that in use the pulsating DC. output of the power unit of FIG. 2 is supplied to a circuit constituting the central cylindrical body 12 (the indifferent electrode), the hand and body of the subject using the apparatus, the electrolyte covered (active) spherical electrode 32, and the cartridge 36 including the septum 42, conduit 64, and pin 62, and that the leadsV or conduits to the output of the power unit may be reversed from the manner illustrated in FIG. 2 so as to constitute the spherical electrode a cathode and the cylindrical bodysection an anode.
Thus, for example, compounds which are effectively cationic, may be successfully iontophoresed when the spherical electrode serves as the anode. Examples of suitable cationic medicaments include inter alia, anti-histaminics such as benedryl, topical anesthetics including itch and/or pain relieving agents such as procaine, autonomic drugs including vasoconstrictors and vasodilators such as acetylcholine, atropine, and epinephrine, agents of clinical interest such as histamine, and the like. Simf ilarly, compounds which are effectively anionic may successfully be iontophoresed when the spherical electrode serves as thercathode, examples thereof including, inter alia, anti-inllammatory agents such as cortisone phosphate, rubefacients such as salicylic acid, antiperspirants such as sodium malonate, and the like.
The driving voltage and pulse width and repetition rate will vary with, inter alia, the tissue surface being treated, the chemical medicament being administered, and the individual subject involved. In general, it is possible to increase the effective amount of ionized medicament applied by increasing the current flow and the time or duration 'ofthe application. Normally it will be desired to increase the applied voltage to the limit permitted by the onsetof the subjectsperception of the iontophoretic current, the capacity of the material administered to produce 'local tissue injury, and the pharmacological potency or fil toxicity of the material administered or the dosage desired, in order to minimize the time required to perform the administration of materials by iontophoresis.
The pulse width and repetition rate to be employed may be varied widely, and non-pulsating direct current may also be used, the extent of iontophoretic transport 'of materials into the skin or other tissues being proportional to the coulombs of electric current passed thereinto. (In the case of a pulsating direct current, this factor is a function of the sum of the pulse widths per unit time, the pulse amplitude or voltage, and the time of application.) However, it has been found that in certain cases involving the use of pulsating direct current, there is a speciiic combination of pulse frequency and pulse width which produces a maximum ion effect. For example, in the case of the iontophoretic application of histamine or of antiperspirant aluminum salts a pulse frequency of 1,000 pulses per second and a pulse width of approximately 60() microseconds produce a maximum effect and are therefore preferred.
An important advantage of the use of a high frequency pulsating direct current over a conventional direct current source is a significant decrease in the subjective sensation of current ow on the part of the user. Thus, a subjects awareness of current flow is diminished permitting a substantial increase in applied voltage before the threshold of discomfort is reached. It has been found that operating conditions suitable for use in a wide variety of applications fall in the range of 3 to 15 volts at a repetition rate of from 60 to 20,000 cycles per second and a pulse width of from 30 to 70% of the period of each cycle. Of course, as indicated hereinabove, conventional non-pulsating direct current may also be employed as desired.
The properties of the electrolyte fluid which is used with the instant apparatus are of considerable importance. The fluid normally comprises a solvent for the ionic medication to be applied, which solvent should be substantially non-conductive such that the medicament constitutes substantially the only current carrier in the electrolyte fluid. Simple aqueous solutions of medicaments have been found generally to be unsuitable for use in iontophoresis from a moving electrode, and it is a feature of the present invention to employ, as an electrolyte fluid, an ionized medicament in an laqueous solution which is thickened with a non-ionic thickener. Normally, the viscosity of such thickened electrolyte fluids will be at least about 150 centipoises, and normally it will fall within the range of from about to 1,000 centipoises at 70 F.
The use of such a thickened aqueous electrolyte diminishes the rate of iiow or drainage of the electrolyte on the electrode and on the skin, provides a uniform layer of electrolyte solution on both surfaces, and provides a valuable lubricating action between the electrode and those surfaces on which it moves. The instant aqueous solutions remain on tissue surfaces at the point of application, and do not run olf or drain away therefrom regardless of the plane of the surface, thus permitting use of the instant apparatus in any position.
Thickeners suitable for use in accordance with the present invention are those which are non-ionic or nonionizing in nature, examples of suitable thickeners including organic gums, hydroxyethylcellulose, hydroxypropyl methylcellulose, polyacrylamides, and the like. An especially preferred thickener is methyl cellulose having a methoxyl content between about 28 and 31% and a hydroxypropyl content between about 2 and 10%, and unless otherwise specifically described, the term hydroxypropyl methyl cellulose as used hereinafter refers to such a material wherein the content by weight of hydroxypropyl groups is about 3% and of methoxyl groups is about 30%.
The thickener which is employed should be inert towards the medicament and the other constituents of the electrolyte fluid in which it is used. The concentration of thickener may be varied widely, a suitable amount thereof being that concentration which confers on the nal solution a viscosity within the range set forth hereinabove. Thus, in the case of the preferred methyl cellulose, typical thickener concentrations may vary from about 0.5 to 3% by weight of the electrolyte uid.
The instant invention has been found to be especially benecial with respect to antiperspirant treatments, suitable medicaments for use thereof including water soluble ionized polyvalent metal salts such as the salts of aluminum 4and zirconium, e.g., aluminum chloride, aluminum chlorhydroxide, aluminum sulfate, aluminum sulfamate, and zirconium oxychloride. Aqueous solutions of these salts may be applied by iontophoresis at current densities from 0.1 to about 2.0 milliamperes per square centimeter of skin in the axilla for periods of 0.5 to 30 minutes without evidence of skin damage or discomfort.
The following examples are given to illustrate additionally the nature of the invention, and it will be understood, of course, that the invention is not limited thereto. In these examples, as elsewhere throughout the present specification and claims, all parts or proportions are by weight unless indicated to be otherwise expressed.
Example l The apparatus of FIG. l is employed by `a subject to treat himself with a aqueous solution of aluminum chlorhydroxide thickened with 1.4% hydroxypropyl methylcellulose to a viscosity of 174 centipoises at 70 degrees F. The apparatus is operated with the ball electrode as an anode, and the conductive portion of the case of the apparatus as an indifferent cathode. A pulsating direct current is applied at a voltage of 13.5 volts, a repetition rate of 1000 cycles per second, and a total On time of 60% of the duty cycle. (The current density corresponds to approximately 2 milliamperes per square centimeter of contact between the fluid covered electrode and the skin.) The indifferent cathode contacts the palm of the subject, and the anode, which is covered by a iilm of the aluminum chlorhydroxide solution, is applied to a shaven axilla with moderate pressure using a uniform massaging motion over the entire surface thereof for a period of 2 minutes. The subject experiences only a slight tingling at the onset of current flow, which is not regarded as unpleasant.
Highly eifective anti-perspirant action results, lasting for several days after the application.
Example Il A subject applies a 5% aqueous solution of dihydroXy acetone thickened with 1.4% hydroxypropyl methyl cellulose to a viscosity of approximately 330 centipoises at 70 degrees F. to his face and forearm. The current characteristics and the mode of application are the same as those set forth in Example I. The time of application is 1 minute for each 3 square inches of skin being treated.
After such application, a tan coloration is produced which is longer lasting and more even than that produced by topical application of the same solution.
Example III A solution of epinephrine l:l0,000 in water, thickened to a viscosity of approximately 330 centipoises at 70 degrees F. with 1.4% hydroxypropyl methyl cellulose, is applied to the beard-growing area of the face of a male subject using the apparatus of fFIG. l. The voltage, pulse repetition rate, pulse width and uniform massaging action of Example I are employed. A 5 minute application to the face of a male subject produces a stiffening of the beard which facilitates shaving, and imparts a sensation of coolness to the treated area,
Example vI V A 1.5% solution of atropine sulfate is applied to the accessible areas of the mucous membranes within the mouth of a subject using the apparatus of FIG. 1. The
solution is thickened to a viscosity of 330 centipoises at 70 degrees F. using 1.4% hydroxypropyl methyl cellulose. Pulsating direct current is employed at a voltage of 5 volts between the ball anode and the indifferent cathode, the repetition rate being 1,000 cycles per second and the On time being 60% of the duty cycle. The duration of the application is 1.5 minutes. Salivation from the areas so treated is substantially diminished.
Example V A 4% aqueous solution of pramoxine hydrochloride thickened to a viscosity of about 300 centipoises at 70 F. -is applied by a subject using the device of FIG. 1 to the anti-cubital area of a forearm exhibiting dermatitis in order to relieve itching. The applied voltage between the electrodes is 13 volts, and the current characteristics and mode of application are the same as those employed in Example I. The duration of the time orf application is one minute for each two square inches treated. Substantial, prolonged relief of itching is achieved.
While there has been disclosed and described that which is at present considered to be the preferred embodiments of the invention, it will be understood, of course, that many changes, modiiications, and substitutions may be made therein without depredatling from the true scope o-f the invention as dened in the following claims.
What is claimed is:
1. A hand-held iontophoresis apparatus comprising a casing, a chamber within said casing for retaining a iluid electrolyte, an opening in said casing, a spherical electrode disposed in said opening and protruding out of said casing, and means, insulated #from said casing, for supplying electric current to said spherical electrode, said spherical electrode being free to rotate and being in communication with said chamber.
2. A hand-held iontophoresis apparatus comprising a casing adapted to be held in the hand, said casing having an electrically conductive section and an electrically nonconducttive section, a fluid reservoir within said casing, means for opening said casing to permit access to said reservoir, an opening in said non-conductive portion of said casing, and a ball electrode disposed in said opening and protruding out of said casing, said ball electrode being free to rotate and being in communication with said reservoir.
3. A hand-held iontophoresis apparatus comprising a cylindrical casing having an electrically conductive section adapted to contact the hand :and an electrically nonconductive tapered end section, an opening in said nonconductive end section, a ball electrode maintained in said opening 4and protruding out of said nonconductive portion of said casing, an electrolyte-iilled cartridge within said casing, ian opening in said cartridge in communication with rand adapted with to supply electrolyte fluid to said ball electrode, means for opening said casing to permit replacement of said cartridge, an electrical storage battery contained within `said casing, and means for supplying electric power from one terminal of said battery to the said conductive portion of said easing and from the other terminal of said battery to said ball electrode.
4. A hand-held iontophoresis apparatus ras set forth in claim 3 containing means for converting electric power from said ystorage cell into pulsating direct current.
5. A hand-held iontopho-resis apparatus comprising a casing adapted to be held in the hand, said casing having an electrically conductive section and an electrically nonconductive section, a stonage battery within said casing, a ui-d reservoir within said casing, means for opening said casing to permit access to said reservoir, an opening in said non-conductive portion of said casing, and a ball electrode disposed in said opening and protruding out of said casing, said ball electrode being free to rotate and being in communication with said reservoir.
6. A hand-held iontophoresis apparatus comprising a casing adapted to be held in the hand, said casing having an electrically Iconductive section and an electrically nonconductive section, a storage battery Within said easing, r'neans Within said easing for recharging said storage battery from yan external source of alternating electric current, a fluid reservoir within said casing, means for opening said `casing to permit access to said reservoir, an opening in said nonJconductive portion of said casing, and a ball electrode disposed in said opening and protruding ont of said casing, said ball electrode being free to rotate and being in communication with said reservoir.
Muir Mar. s, 189s Linn May 9, 1905 Kovacs Robinson Oct. 15, De Jong Aug. 24, Landauer Aug. 17, Patterson Oct. 14, Andresen Nov. 17, Seyer Nov. 19,
FOREIGN PATENTS Great Britain Sept. 14,
OTHER REFERENCES on Transfer in Electrotherapy and Light Therapy, fifth edition, published 1947 by Lea and Febiger, pp. 151-160.
Glasser: Medical Physics, page 991, vol. I1, published
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|Clasificación de EE.UU.||604/20, D24/214, 401/209, 607/153, 313/359.1|
|Clasificación internacional||A61N1/30, A61N1/32|
|Clasificación cooperativa||A61N1/044, A61N1/0448, A61N1/325, A61N1/303, A61B2018/1417|
|Clasificación europea||A61N1/04E1I1S, A61N1/04E1I3, A61N1/32E, A61N1/30B|