Method and apparatus for skin absorption enhancement and transdermal drug delivery Number:7,520,875 from the United States Patent and Trademark Office (PTO) owispatent

Title: Method and apparatus for skin absorption enhancement and transdermal drug delivery

Abstract: A system for enhancing absorption of a substance to be provided on a region of a patient's skin, includes a probe configured to provide the substance to the region of the patient's skin, the probe including a flexible tape with a plurality of cavities, and with an electrically conductive element, such as a conductive wire, provided at one end of each of the cavities. A substance holding material, such as gauze stripes, temporarily holds the substance to be provided on the region of the patient's skin, the substance holding material being provided in each of the cavities. A pulse generator generates a sequence of bursts of electrical pulses to the electrically conductive elements provided within the cavities, so as to provide the bursts of electrical pulses to the region of the patient's skin.

Patent Number: 7,520,875 Issued on 04/21/2009 to Bernabei

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Inventors:	Bernabei; Gian Franco (Florence, IT)
Assignee:	Mattioli Engineering Ltd. (London, GB)
Appl. No.:	11/657,551
Filed:	January 25, 2007

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Related U.S. Patent Documents

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	Application Number	Filing Date	Patent Number	Issue Date
	10992597	Nov., 2004
	10784913	Feb., 2004	7083580
	10448468	May., 2003	6980854
	10397533	Mar., 2003	7010343
	10201644	Jul., 2002	6748266
	10074234	Feb., 2002	6743215
	09942044	Aug., 2001	6687537
	09922927	Aug., 2001	6535761
	60281808	Apr., 2001

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Current U.S. Class:	604/501 ; 604/20
Current International Class:	A61M 31/00 (20060101); A61N 1/30 (20060101)
Field of Search:	604/20,501 607/2

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	1077143		Jul., 1967		GB
	1-274774		Nov., 1989		JP
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	10-174704		Jun., 1998		JP
	WO 99/44678		Sep., 1999		WO
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	WO 00/44438		Aug., 2000		WO
	WO 02/49717		Jun., 2002		WO
	WO 03/039620		May., 2003		WO

Primary Examiner: Bockelman; Mark W
Attorney, Agent or Firm: Foley & Lardner LLP

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Parent Case Text

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CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

This application claims priority to U.S. Provisional Application 60/281,808, filed Apr. 6, 2001, and whereby this application is a continuation-in-part of U.S. patent application Ser. No. 10/992,597, filed Nov. 19, 2004, which in turn is a continuation-in-part of U.S. patent application Ser. No. 10/784,913, filed Feb. 24, 2004, now U.S. Pat. No. 7,083,580, which in turn is a continuation-in-part of U.S. patent application Ser. No. 10/448,468, filed May 30, 2003, now U.S. Pat. No. 6,980,854, which in turn is a continuation-in-part of U.S. patent application Ser. No. 10/397,533, filed Mar. 27, 2003, now U.S. Pat. No. 7,010,343, which in turn is a continuation-in-part of U.S. patent application Ser. No. 10/201,644, filed Jul. 24, 2002, now U.S. Pat. No. 6,748,266, which in turn is a continuation-in-part of U.S. patent application Ser. No. 10/074,234, filed Feb. 14, 2002, now U.S. Pat. No. 6,743,215, which in turn is a continuation-in-part of U.S. patent application Ser. No. 09/942,044, filed Aug. 30, 2001, now U.S. Pat. No. 6,687,537, which in turn is a continuation-in-part of U.S. patent application Ser. No. 09/922,927, filed Aug. 7, 2001, now U.S. Pat. No. 6,535,761, each of which is incorporated in its entirety herein by reference.

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Claims

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What is claimed is:

1. A system for enhancing absorption of a substance to be provided on a region of a patient's skin, comprising: a probe configured to provide the substance to the region of the patient's skin, the probe including a flexible tape with a plurality of cavities, and with an electrically conductive element provided at one end of each of the cavities; a substance holding material configured to temporarily hold the substance to be provided on the region of the patient's skin, the substance holding material being provided in each of the cavities; and a pulse generator configured to generate a sequence of bursts of electrical pulses to the electrically conductive elements provided within the cavities, so as to provide the bursts of electrical pulses to the region of the patient's skin, wherein the pulse generator includes a first set of transformers and a second set of transformers, the first and second sets being in number greater than one, wherein only one of the first set of transformers and only one of the second set of transformers outputs electrical pulses at any given point in time, and wherein the plurality of cavities comprises a first set of even-numbered cavities and a second set of odd-numbered cavities interleaved with each other, and wherein the first set of transformers is electrically connected only to the first set of even-numbered cavities and the second set of transformers is electrically connected only to the second set of odd-numbered cavities.

2. The system according to claim 1, wherein no pulses are output by the pulse generator in between consecutive bursts of electrical pulses.

3. The system according to claim 1, further comprising: vibrating means for providing mechanical vibrations to the region of the patient's skin at a same time the sequence of bursts are applied to the region of the patient's skin, wherein the vibrating means corresponds to a plurality of piezoelectric units disposed at different locations on the flexible tape.

4. The system according to claim 3, wherein the plurality of piezoelectric units are disposed in a matrix format in a plurality of rows and columns on a surface of the flexible tape.

5. The system according to claim 1, wherein the substance holding material comprises a plurality of gauze stripes.

6. The system according to claim 1, wherein the transformer includes peak current limiting means for maintaining a current applied to the patient's skin to be below a predetermined current level.

7. The system according to claim 6, wherein the peak current limiting means outputs pulses of successively decreasing voltage levels in each of said bursts of electrical pulses, in order to maintain a peak current at the patient's skin at substantially the same value throughout a time period when each of said bursts of electrical pulses are output to the patient's skin.

8. A method of transdermal drug delivery to be provided to a patient's skin, comprising: performing a dermabrasion treatment of the patient's skin so as to lower a skin impedance to below a first value; and providing, by way of a probe that comprises a flexible tape, a plurality of cavities, and a substance holding material provided in each of the cavities and which holds a drug to be delivered to the patient's skin, at least one burst of electrical pulses to the patient's skin that has been dermabrasion treated; and controlling an amount of current to be applied to the patient's skin in the at least one burst of electrical pulses, wherein the plurality of cavities comprises a first set of even-numbered cavities and a second set of odd-numbered cavities interleaved with each other, and wherein a first set of the electrical pulses in the at least one burst of electrical pulses is applied only to the first set of even-numbered cavities and wherein a second set of the electrical pulses in the at least one burst of electrical pulses is applied only to the second set of odd-numbered cavities.

9. The method according to claim 8, wherein the at least one burst of electrical pulses comprises a plurality of alternate-polarity pulses.

10. The method according to claim 8, wherein the at least one burst of electrical pulses comprises a plurality of square-shaped, current-stabilized pulses.

11. The method according to claim 8, wherein the amount of current to be applied to the patient's skin is controlled to be 500 Ohms per square centimeter or less.

12. The method according to claim 8, wherein the amount of current to be applied to the patient's skin is controlled to be 2000 Ohms per square centimeter or less.

13. A method for performing transdermal drug delivery to a patient's skin, comprising: providing, by way of a probe, a plurality of bursts of electronic pulses to the patient's skin at a same time a drug is applied to the patient's skin; and in between the providing of the plurality of bursts of electronic pulses to the patient's skin, applying either alternate-polarity square pulses or sinusoidal pulses to the patient's skin, wherein the probe includes a flexible tape with a plurality of cavities in which a substance holding material is disposed in each of the cavities, the substance holding material holding the drug to be applied to the patient's skin, wherein the bursts of electronic pulses are provided in sequential order to a plurality of electronic pulse signal lines respectively provided for an electrode array disposed on the probe, wherein the bursts of electronic pulses are provided by way of a plurality of pulse generators respectively connected to the plurality of electronic pulse signal lines in which the plurality of pulse generators includes a first set of pulse generators connected to a first set of the plurality of cavities that are not directly adjacent to each other, and a second set of the plurality of cavities that are not directly adjacent to each other, wherein the plurality of pulse generators are selectively turned on and off by way of a processor such that the first set of pulse generators only provides electrical pulses to the first set of the plurality of cavities and the second set of pulse generators only provides electrical pulses to the second set of the plurality of cavities.

14. The method according to claim 13, wherein the plurality of bursts of electronic pulses and the alternate-polarity square pulses or the sinusoidal pulses to the plurality of electrodes are created by way of a transformer.

15. The method according to claim 13, wherein the bursts of electronic pulses are provided to the plurality of cavities by way of an electronic switch, wherein corresponding ones of the plurality of electronic pulse signal lines are electrically connected to the plurality of pulse generators in a sequential manner under control of the processor.

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Description

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BACKGROUND OF THE INVENTION

A. Field of the Invention

The invention relates to application of a substance to a patient's skin, whereby the substance is an ascorbic acid, lidocaine, collagen, or other type of skin treatment substance.

B. Description of the Related Art

It is known that an electrical pulse applied to the skin is useful in order to increase the absorption of a substance previously applied to the skin, whereby this technique is known as electroporation. Such a substance to be applied to the skin may be a liquid, a gel, a lotion, or a cream, for example.

It is desired to provide an apparatus and a method to increase the absorption of a substance to be applied to the skin, in order to obtain an increased (e.g., moisturizing) affect of the substance applied to the skin, as well as to obtain a fairly even absorption of the substance to the skin.

SUMMARY OF THE INVENTION

The present invention is directed to an apparatus and a method for enhancing the absorption of a substance to be applied on the skin.

According to one aspect of the invention, there is provided a system for enhancing absorption of a substance to be provided on a region of a patient's skin, which includes a probe configured to provide the substance to the region of the patient's skin, the probe including a flexible tape with a plurality of cavities, and with an electrically conductive element provided at one end of each of the cavities. The system also includes a substance holding material configured to temporarily hold the substance to be provided on the region of the patient's skin, the substance holding material being provided in each of the cavities. The system further includes a pulse generator configured to generate a sequence of bursts of electrical pulses to the electrically conductive elements provided within the cavities, so as to provide the bursts of electrical pulses to the region of the patient's skin.

According to another aspect of the invention, there is provided a method of transdermal drug delivery to be provided to a patient's skin, which includes performing a dermabrasion treatment of the patient's skin so as to lower a skin impedance to below a first value. The method also includes providing, by way of a probe that comprises a flexible tape, a plurality of cavities, and a substance holding material provided in each of the cavities and which holds a drug to be delivered to the patient's skin, at least one burst of electrical pulses to the patient's skin that has been dermabrasion treated. The method further includes controlling an amount of current to be applied to the patient's skin in the at least one burst of electrical pulses.

According to yet another aspect of the invention, there is provided an apparatus for performing transdermal drug delivery to be provided to a patient's skin. The apparatus includes a probe having a plurality of electrodes on a head portion of the probe, the plurality of electrodes being configured to apply a plurality of bursts of electronic pulses to the patient's skin at a same time a drug is applied to the patient's skin, and the plurality of electrodes being configured to apply either alternate-polarity square pulses or sinusoidal pulses to the patient's skin in between adjacent ones of the plurality of bursts of electronic pulses. The probe includes a flexible tape with a plurality of cavities in which a substance holding material is disposed in each of the cavities, the substance holding material holding the drug to be applied to the patient's skin.

During operation, electrical pulses are provided to the skin by way of the electrodes on the head of the probe, and, at the same time, mechanical vibrations are provided to the skin by way of the vibrating head portion, whereby a substance to be applied to the skin is disposed within the trough surrounding the central electrode. The substance is absorbed within the skin due to the skin pores opening up as a result of the electrical pulses and mechanical vibrations being applied to the skin at the same time. Alternatively, only electrical pulses are provided to the skin, which may not provide as good a skin absorption effect as using both electrical pulses and mechanical vibrations, but which provides a cheaper implementation which is suitable for certain situations. Also, gauze pads may be provided on the probe, whereby the gauze pads are soaked with a particular solution or solutions (e.g., hydrogel, lidocaine, or both) to be applied to the patient's skin.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing advantages and features of the invention will become apparent upon reference to the following detailed description and the accompanying drawings, of which:

FIG. 1A is a side view of a vibration mechanism that is disposed within an apparatus according to the present invention;

FIG. 1B is a front view of the vibration mechanism of FIG. 1A;

FIG. 2A shows an array of electrodes provided on an outer surface of the vibration plate that faces the skin, according to a first embodiment of the invention;

FIG. 2B shows an array of electrodes provided on an outer surface of the vibration plate that faces the skin, according to a second embodiment of the invention;

FIG. 2C shows an array of electrodes provided on an outer surface of the vibration plate that faces the skin, according to a third embodiment of the invention;

FIG. 3 shows a side view of a head of a probe that is used to provide both electrical and mechanical stimulation to the skin, in order to have a substance previously applied to the skin to be absorbed better, according to the invention;

FIG. 4 shows an electrical diagram of a pulse generator that provides electrical pulses to an array of electrodes disposed on a vibrating plate provided at a head-end of the probe, according to one possible configuration of an apparatus according to the invention;

FIG. 4A shows a train of square-wave pulses that are input to the pulse generator of FIG. 4;

FIG. 4B shows a train of exponential pulses that are output from the pulse generator of FIG. 4;

FIG. 5 shows one configuration of a hand-held probe that is used to provide both electrical and mechanical stimulation to the skin, according to one or more embodiments of the invention;

FIG. 6 shows a current generator connection according to a fourth embodiment of the invention;

FIG. 7 shows elements provided at the head portion of a probe, according to a fifth embodiment of the invention; and

FIG. 8 shows a front view of the head portion of the probe according to the fifth embodiment of the invention;

FIG. 9 shows a front view of the head portion of the probe according to an eighth embodiment of the invention;

FIG. 10 shows a first section view of the head portion of the probe according to the eighth embodiment of the invention, whereby suction is not being applied to the skin;

FIG. 11 shows a second section view of the head portion of the probe according to the eighth embodiment of the invention, in which suction is being applied to the skin;

FIG. 12 shows a structure of an electroporation device according to a ninth embodiment of the invention;

FIG. 13 shows components used to couple electrodes and wires to a head of the electroporation device according to the ninth embodiment of the invention;

FIG. 14 shows a side view of the head of a probe used in an apparatus according to the ninth embodiment of the invention;

FIG. 15 shows a back view of the head of a probe, along with transformers shown, in an apparatus according to a tenth embodiment of the invention;

FIG. 16 shows a front view of the head of a probe used in an apparatus according to the tenth embodiment of the invention;

FIG. 17 shows a front view of the head of a probe having three electrodes, which is used in an apparatus according to an eleventh embodiment of the invention;

FIG. 18 shows a back view of the head of a probe having three electrodes, along with transformers providing electronic pulses to the three electrodes, which is used in an apparatus according to the eleventh embodiment of the invention;

FIG. 19 shows staggered square-wave input pulses and exponential outputs pulses with respect to the three transformers which is used in an apparatus according to the eleventh embodiment of the invention; and

FIG. 20 shows a gauze pad provided between a probe (according to any of the embodiments of the invention) and a patient's skin, according to a twelfth embodiment of the invention.

FIGS. 21-24 show different views of a skin treatment device according to a thirteenth embodiment of the invention.

FIGS. 25-27 show one possible implementation of a skin treatment device according to a fourteenth embodiment of the invention.

FIGS. 28-31 show another possible implementation of a skin treatment device according to the fourteenth embodiment of the invention.

FIGS. 32A, 32B and 32C show one possible implementation of a skin treatment device according to a fifteenth embodiment of the invention.

FIGS. 33A and 33B show another possible implementation of a skin treatment device according to the fifteenth embodiment of the invention.

FIGS. 34A, 34B and 34C show still another possible implementation of a skin treatment device according to the fifteenth embodiment of the invention.

FIGS. 35 and 36 still another possible implementation of a skin treatment device according to a sixteenth embodiment of the invention.

FIGS. 37-40 show still another possible implementation of a skin treatment device according to a seventeenth embodiment of the invention.

FIGS. 41-43 show still another possible implementation of a skin treatment device according to an eighteenth embodiment of the invention.

FIGS. 44 and 45 show still another possible implementation of a skin treatment device according to a nineteenth embodiment of the invention.

FIGS. 46-48 show still another possible implementation of a skin treatment device according to a twentieth and twentyfirst embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Preferred embodiments of the invention will be described in detail below, with reference to the accompanying drawings.

Based on experimental tests on the skin, it has been found by the inventor that after one or more pulses are applied between two points on the skin, transpiration (or absorption) in the area between the two points on the skin increases. The pulses that give optimal results are exponential pulses that are generated by a charged capacitor that is discharged on at least two separate points on the skin.

These experimental results have been utilized by the inventor in order to develop an apparatus and method that maintains the transpiration of the skin at a high level, so that the skin can readily absorb a gel, liquid, lotion, cream, or drug that is applied to the skin. The drug may be used to treat skin melanoma and/or cancerous tumors located just below the skin surface, for example.

The apparatus according to an embodiment of the present invention applies a sequence of pulses over an area or skin, by using an array of electrodes that are placed in contact with the skin. The array of electrodes are provided on a vibrating plate at the head of a probe, such as a hand-held probe 500 as shown in FIG. 5. The array of electrodes may be a configured as shown in FIG. 2A in a first embodiment, whereby odd rows of electrodes are electrically connected to each other, and thereby to a first output of a pulse generator 400 (see also FIG. 4) via a first electrical connection. The even rows of electrodes are electrically connected to each other, and also to a second output of the pulse generator 400 via a second electrical connection. The array of electrodes on the vibrating plate may alternatively be configured as shown in FIG. 2B in a second embodiment, whereby odd rows of round electrodes are electrically connected to each other, and thereby to the first output of the pulse generator 400 via a first electrical connection. The even rows of round electrodes are electrically connected to each other, and thereby to the second output of the pulse generator 400 via a second electrical connection.

The increase of the transpiration of the skin that is obtained by way of the present invention has the effect of increasing the absorption of liquids, creams, lotions, gels, or skin treatment drugs (or other kinds of drugs) that have been previously provided on the skin in the area between where the electrodes are applied to the skin.

The electrical pulses that are applied on the skin in order to enhance the transpiration of the skin are pulses obtained by a discharge of a capacitor on the skin. That is, the skin acts as a capacitive load when a probe is applied to the skin. A square-wave pulse input to a primary winding of the transformer 410 of FIG. 4, with an output of the secondary winding of the transformer 410 being coupled to the skin by way of the electrodes, provides the same effect as a discharging capacitor. However, by using a transformer 410 instead of a capacitor, one can obtain current control with respect to electrical pulses applied to the skin, so that the amount of current applied to the skin during treatment of the skin does not exceed a predetermined maximum current value.

The exponential pulses are generated during the rising edge and falling edge of each square-wave input pulse that is input to the transformer 410 from a square-wave pulse generator, and have opposite sign (positive exponential pulse due to the rising edge of a square-wave input pulse, negative exponential pulse due to the falling edge of the same square-wave input pulse). With the use of such a pulse generator 400 as shown in FIG. 4, it is possible to apply a burst of separate pulses (e.g., 500 to 1500 per second) to the skin, with adjacent pulses being of opposite polarity and which provides a transpiration effect better than just providing one pulse or many pulses of the same polarity to the skin.

Also, by outputting bursts of pulses to the skin in which each burst of pulses includes adjacent pulses in the same burst of opposite polarity (e.g., +-+-+-+-+- . . . ), any potential current buildup in the skin is obviated due to the cancellation effect cause by utilizing adjacent pulses of opposite polarity. This is in contrast to the conventional devices that output electrical pulses of the same polarity, which may result in current buildup in a patient's skin, which may lead to damaging effects caused to the skin as a result of the current buildup.

As explained above, a burst pulse generator utilizes an inductive element (e.g., a transformer) instead of a capacitor, so that the current-to-be-applied to a patient's skin can be controlled. In conventional devices that utilize a capacitor for their electrical pulse generator, when that capacitor is coupled to a patient's skin, the resultant circuit amounts to a first capacitor (that being the capacitor of the pulse generator) in parallel with a second capacitor (that being the capacitor due to the capacitive/resistive effect of a skin operating as a load). When a voltage is applied to the skin by way of an electrical pulse, the discharge of a voltage from the first capacitor to the second capacitor results in a very large current spike for an initial short period of time, whereby that large current spike cannot be readily controlled. This can result in negative effects to the patient's skin caused by the large current spike. By utilizing an inductive element (e.g., a transformer) instead of a capacitive element in the pulse generator, as shown in FIG. 4 of the drawings, no current spike results when a probe with electrodes providing electrical pulses is coupled to a patient's skin (since the "capacitive skin" smoothly receives the current and voltage from the "inductive pulse generator").

Switching transistor 430 provides square-wave pulses as shown in FIG. 4A to the primary winding of the transformer 410, as shown in FIG. 4. The pulses generated by the pulse generator 400 of FIG. 4, when the load is a pure resistance (or inductive or other type of reactive load), is a sequence of exponential decay pulses of opposite symmetrical polarities, as shown in FIG. 4B. Such a circuit that includes the pulse generator 400 provides an excellent coupling to the impedance of the skin. Moreover, in addition to the current control described above, the inductance of the transformer 410 together with the capacitance of the skin generates a resonant circuit, which is desirable to achieve an opening of the skin pores or membranes.

The voltage waveform is conveniently modified when applied to the skin due to the fact that the electrical equivalent circuit of the skin is a resistance and a capacitance in parallel. The resulting voltage waveform has a longer rise time (due to the RC time constant), and is dependent upon the capacitance of the skin, while maintaining the same peak current and the same exponential decay waveform.

Such a circuit according to the first embodiment gives an advantage in comparison to traditional pulse generators that deliver pulses of a predefined value and shape of tension or current. By way of the present invention according to the first embodiment, it is possible to deliver higher energy value per pulse, and also at the same time avoid possible damage to the skin that would occur if high current amounts were applied to the skin. The circuit utilized in the first embodiment self adjusts the value of the current, voltage and waveform shape. In particular, the impedance of the skin decreases after the first pulse is applied to the skin. In this way, the voltage of the first pulse is higher than subsequent pulses, since the impedance of the skin is higher at the time the first pulse is applied to the skin. The voltage of the second and following pulses applied to the skin decreases with the decreasing of the impedance of the skin, while maintaining the peak current at the same or almost the same value.

Typical values of current and voltage are provided herein. Case 1: load impedance of 10 kohm, peak voltage of 100 V, peak current of 10 milliamperes, pulse width of 220 microseconds. Case 2: load impedance of 1 kohm, peak voltage of 10 V, peak current of 10 milliamperes, pulse width of 220 microseconds. The pulses are preferably delivered in bursts, where the burst rate is the same or nearly the same as the mechanical vibration rate. A typical value of the burst rate (and mechanical rate) is between 40 Hz and 100 Hz.

The inventor of this application has also realized that the use of mechanical vibrations at the same time that the electrical pulses are applied to skin, and at a same or nearly the same frequency as the burst pulse rate, results in a patient having a greater tolerance to the strength (current and voltage) of the electrical pulses applied to the patient's skin. For example, using a electrical pulse burst rate of 50 Hz (that is the rate between bursts of pulses), mechanical vibrations may be provided at a range of between 40 to 60 Hz at the same time that the electrical pulse bursts are applied to the skin, to provide a "masking effect." The inventor has also found that utilizing mechanical vibrations at or around (e.g., +/-10% of) the fundamental frequency of the electrical pulse burst rate, at or around the first harmonic of the electrical pulse burst rate, at or around the second harmonic of the electrical pulse burst rate, and/or at or around the third harmonic of the electrical pulse burst rate, gives the patient a "good sensation" so that he/she can tolerate a higher strength of electrical pulses being applied to his/her skin at the same time. Thus, for a 50 Hz electrical pulse burst rate, mechanical vibrations may be applied to the patient's skin at the same time, with the mechanical vibration rate being either 40 to 60 Hz, 90 to 110 Hz, 140 to 160 Hz, and/or 190 to 210 Hz. By having mechanical vibrations applied to the patient's skin at the same time that the electrical pulse bursts are applied to patient's skin, the patient's discomfort level caused by the tinging sensation of the electrical pulses is lessened (e.g., masked somewhat).

Normally, when a square wave is applied to the skin, due to the capacitive effect of the skin, it is possible to obtain about a three microsecond time constant exponential decay current. This is what happens when a square wave voltage is applied to a circuit that corresponds to a resistor in parallel with a capacitor.

With such a circuit, only the peak current is enhanced, charging to a maximum allowable voltage the skin capacitance by applying an electrical energy equal to the magnetic energy of the transformer 410. This effect most likely provides for the opening of the cell membranes or pores of the skin (to achieve the transpiration effect) only during the time when each pulse is applied to the skin.

The effect of applying the probe to the skin is that the skin vibrates due to the electrical pulses applied by way of the array of electrodes. The electrical pulses are preferably applied at a fixed frequency between 200 and 10,000 Hz (optimally at a frequency value between 2,500 to 3,000 Hz), and are grouped in burst of pulses (e.g., each burst may correspond to 100 to 1000 separate pulses that have opposite polarities with respect to adjacent pulses in the same burst of pulses). The ON time of each burst is a fixed value between 5 to 50 milliseconds, and the OFF time between two consecutive bursts is a fixed value between 5 to 50 milliseconds (the preferred burst ON time is 10 milliseconds and the preferred OFF time between consecutive bursts is 10 milliseconds).

As described above, the electrical pulses applied to the skin by way of the electrodes are preferably exponential pulses with peak-to-peak voltage of 160 V at a fixed frequency between 2,500 to 3,000 Hz. One way of providing such electrical pulses is by an electrical structure that corresponds to a pulse generator 400 as shown in FIG. 4, in which a transformer 410 is used as an element of the pulse generator 400.

The transformer 410, as well as the other elements of the pulse generator 400, are preferably housed within the probe 500 of FIG. 5.

Referring back to FIG. 4, the primary winding 420 of the transformer 410 is driven by a transistor 430 that is switched on and off, and the secondary winding 440 of the transformer 410 is directly applied to the array of electrodes (see FIG. 1A or 1B) with an electrical resistance 450 provided therebetween. The electrical resistance 450 may be 200 Kohm or some value in that range (e.g., 100 Kohm to 500 Kohm), and is provided in order to avoid high voltages when the array of electrodes are not applied to the skin, so that in that case it operates as an open circuit. In such a situation, the peak-to-peak voltage is 400 V or thereabouts.

Along with the electrical pulses applied to the skin, a mechanical vibration is also provided to the skin in the first embodiment in order to increase the absorption of a substance that is applied on the skin.

The absorption effect is enhanced by the simultaneous increase of transpiration, whereby the absorption effect is greatest when the mechanical vibration is synchronized in phase and in frequency with the electric pulse application. Thus, in the example discussed above, while the electrical burst of pulses (at 2,200 Hz) are provided to the skin at a burst ON/OFF frequency, e.g., 50 Hz, by way of an electrode array, the skin is also mechanically vibrated at the same frequency, e.g., 50 Hz, by way of the vibrating plate. The mechanical vibration and the electrical burst application are also preferably provided in phase with respect to each other, in order to increase the skin absorption effect. There are several well known ways to achieve this frequency and phase synchronization. In the preferred embodiments described herein, an optical sensor (not shown) detects the movement of the eccentric of a motor that is used to provide the mechanical vibrations (see FIGS. 1A and 1B, for example), and gates the burst of electrical pulses based on the detected movement.

Thus, in the example discussed above, while the burst of electrical pulses are provided to the skin by way of the electrode array, the skin is also mechanically vibrated at the same frequency by way of the vibrating plate. The mechanical vibration and electrical pulse application is also preferably provided in phase with respect to each other, in order to increase the skin absorption effect.

Moreover, the absorption effect is further enhanced when the mechanical vibration is applied orthogonal to the surface of the skin. While Applicant does not intend to be tied down to any particular theory of operation, one possible explanation of the physical phenomena of one or more embodiments of the present invention is that, while the electrical pulses "stretch" the skin, thus increasing periodically the diameter of the pores of the skin, at the same time the mechanical vibration "pumps" the substances (gel, liquid or cream) inside the skin (through the opened pores). The mechanical and electrical synchronization achieves the effect that the "pumping" action (due to the mechanical stimulation of the skin) takes place at the same instant in time that the pores are at their maximum "open" diameter (due to the electrical stimulation of the skin).

The apparatus according to a first embodiment the present invention includes a probe having two main parts:

A) a handle containing a power source (e.g., batteries) and a pulse generator; and

B) a vibrating head containing components for generating the vibration and also containing an array of electrodes.

The vibrating head, in a preferred configuration of the first embodiment, includes a D.C. electrical motor for generating vibrations to the skin. FIGS. 1A and 1B show two different views of the D.C. electrical motor 110, the rotating shaft of the D.C. electrical motor 110 is an eccentric 120 to thereby provide eccentric motion. The eccentric motion, during rotation of the D.C. electrical motor 110, generates a vibration onto the vibrating plate 130 (that is directly coupled to the D.C. electrical motor 110) that is at the same frequency of the rotation of the D.C. electrical motor 110 (e.g., 50 Hz or 60 Hz or some other desired frequency). Other ways of causing vibrations in synchronization with the providing of electrical pulses to a patient may be contemplated while remaining within the scope of the invention. Note that the use of mechanical pulses at the same or nearly the same rate as bursts of electrical pulses, but not necessarily in synchronism with each other, as described earlier, provides a good effect in that it lessens the patient's discomfort level associated with the buzzing and tinging sensation caused by receiving electrical pulses to the skin alone. Also, the use of adjacent pulses in each burst of opposite polarity to each other results in no current buildup to the patient's skin, which can be a detrimental effect of conventional devices that use electrical pulses of the same polarity to be provided to a patient's skin.

As explained earlier, FIG. 4 shows circuitry for providing electrical pulses to the array of electrodes shown in FIGS. 2A and 2B. The circuitry of FIG. 4 corresponds to a pulse generator 400, and is preferably disposed within the housing of the probe 500 of FIG. 5. The electrical pulses generated by the pulse generator 400, when those pulses are provided to the skin, preferably are exponential pulses with peak-to-peak voltage of 160 V at a frequency of between 2,500 Hz to 3,000 Hz. Of course, other peak-to-peak voltage values (e.g., 100 V to 200 V) and operating frequencies (50 Hz to 15,000 Hz) may be employed, while remaining within the scope of the invention as described herein. Alternatively, sawtooth or sinusoidal pulses may be provided to the electrodes, but exponential pulses appear to provide better skin transpiration results.

FIGS. 1A and 1B show the vibrating plate 130 that is physically coupled to the D.C. electrical motor 110. The vibrating plate 130 preferably is 50.times.50 mm in size (other sizes are possible while remaining within the scope of the invention), where parallel metallic stripes are deposited on it as shown in FIG. 2A, in order form the array of electrodes. The vibrating plate 130 is caused to vibrate at the same phase and frequency as the electrical pulses provided to the skin by way of the array of electrodes (disposed on the vibrating plate), in order to enhance the skin absorption effect.

As shown in FIG. 2A, which shows a first embodiment of an electrode array 210 that is provided on a skin-side surface of the vibrating plate 130, five parallel metallic stripes 220 are provided, each preferably of a size of 50 mm.times.4 mm. Each of the five electrodes 220 are preferably 6 mm apart from adjacently-positioned electrodes. The electrodes 220 are alternately electrically connected (e.g., the first, third and fifth row are electrically connected to each other by way of electrical line 250; and the second and fourth rows are electrically connected to each other by way of electrical line 260). Other electrode array configurations are possible while remaining within the scope of the invention, such having a number of electrodes greater than two, such as having seven or eight electrodes.

FIG. 2B shows a second embodiment of an electrode array that is provided on a skin-side surface of a vibration plate. In FIG. 2B, there are provided 25 round electrodes 230 each of 4 mm diameter, each separated at least 6 mm from adjacently-positioned round electrodes. The round electrodes 230 are alternately electrically connected to each other (e.g., the electrodes on the first, third and fifth rows are electrically connected to each other by way of electrical line 270; and the electrodes on the second and fourth rows are electrically connected to each other by way of electrical line 280). The spacing between the electrodes 230 shown in FIG. 2B may vary between 1 to 20 mm and the size of each of the electrodes 230 may vary between 1 to 20 mm in diameter.

FIG. 2C shows an array of electrodes provided on an outer surface of the vibration plate that faces the skin, according to the third embodiment of the invention. In FIG. 2C, there are provided electrodes 233 that are disposed on the periphery of the vibration plate, which are electrically coupled to each other, and which are electrically coupled to a first output of the pulse generator 400 by way of a first electrical connection 235. In FIG. 2C, there is also provided a centrally-positioned electrode 237, which is not electrically coupled to any other of the electrodes, and which is electrically coupled to a second output of the pulse generator 400 by way of a second electrical connection 239.

FIG. 3 shows a side view of a vibrating head 310 of a probe that is used to provide both electrical and mechanical stimulation to the skin according to an embodiment of the present invention, in order to have a substance previously applied to the skin be absorbed better. As shown in FIG. 3, the vibrating head 310 includes the array of electrodes 320 provided on a skin-side surface thereof. The array of electrodes 320 may be provided in a manner such as shown in either FIG. 2A or 2B, for example. Between the array of electrodes 320 and the skin 330 there is provided a substance 340 to be absorbed, whereby the substance 340 has been previously applied to the skin 330 (e.g., applied to the skin between 30 seconds to 2 minutes before the probe is to be applied to the skin 330). Application of mechanical vibrations and electrical pulses enhances the absorption of the substance 340 into the skin 330.

FIG. 5 shows one configuration of a hand-held probe 500 that may be used to provide both electrical and mechanical stimulation to the skin, according to one or more embodiments of the invention. The probe 500 is configured to be readily held by one hand of a user. A bottom portion of the probe 500, at which a user's hand is gripped thereon to thereby hold the probe 500, may include an outlet 510 for coupling an electrical cable to an electrical outlet (e.g., wall outlet), so as to provide A.C. voltage to the probe 500 in that manner. Alternatively, battery power may be used, by way of batteries (not shown).disposed within the housing of the probe 500. Battery power may be utilized when A.C. power is not readily available. Also, the pulse generator 400 of FIG. 4 is preferably housed at the handle portion of the probe 500.

The head portion of the probe 500 is where the vibrating plate 130 (see FIG. 1A or 1B) is provided, and also where the D.C. electrical motor 110 (see also FIG. 1A or 1B) that provides the mechanical vibrations to the vibrating plate 130 is preferably provided housed within. The array of electrodes (see FIG. 2A or 2B) are provided on an outer surface of the vibrating plate 130, thereby facing the skin of a user to be treated with the probe 500.

A typical application time of the probe to the skin may be on the order to 10s of seconds up to several minutes.

In a fourth embodiment, as shown in FIG. 6, the output of the pulse generator 400 (see also FIG. 4) is connected to a D.C. current generator 610, which induces a iontophoresis effect in addition to the previously described skin absorption/transpiration effects. The iontophoresis effect is well known to those skilled in the art, and several ionthophoresis electrical generators are currently available in the market, either D.C. or D.C. pulsed. A D.C. current output by the D.C. current generator 610 is applied between the electrodes of the probe and a ground plate that is connected with the patient's body. Depending on the substance to be absorbed into the patient's skin, the patient ground plate connection is coupled to either the positive or the negative of the D.C. current generator 610, in a manner known to those skilled in the art. Instead of using continuous D.C. current, there can alternatively be provided D.C. current pulses that have the same average current value as the continuous D.C. current case, and which have a duty cycle between 5 and 50% and a frequency between 10 and 5000 Hz. In such a case, the peak current of the D.C. current pulses is higher during the pulsed (ON) times.

In a fifth embodiment, as shown in FIGS. 7 and 8, a dispenser or chamber 710, which is configured to hold liquid or cream or gel 720, is integrated in the vibrating head of the probe. The dispenser or chamber 710 is provided between an array of electrodes 705 and the vibrating plate 130. The burst of electrical pulses are applied by way of a conductive roller 740 that dispenses the liquid, and by the array of electrodes 705. A D.C. current as in the third embodiment can also be added between the array of electrodes 705 and the patient's body, to induce a iontophoresis effect as well. While the vibrating head is moved on the patient's skin, the roller 740 delivers the liquid or cream or gel 720 to the patient's skin.

The chamber 710 in which the roller 740 is disposed in the vibrating head can be filled with a liquid, cream or gel substance 720 by way of a removable cap (not shown). In particular, the cap is removed (e.g., screwed off of the head of the probe), and then a user fills the chamber 710, through the liquid inlet 760, with the substance 720 to be provided to the patient's skin. The user then closes the cap (e.g., screws it back onto the liquid inlet 760) to thereby keep the substance 720 within the chamber 710 of the probe until it is ready to be applied to the patient's skin by way of the roller 740.

FIG. 8 shows a front view of the electrodes 705, which are shown as two stripe electrodes that are electrically connected to each other by way of electrical connection 820. Of course, other types of electrode arrays, such as those shown in FIGS. 2A and 2B, can alternatively be used in this fifth embodiment. The exposed surface 830 of the roller 740 that applies the substance to the patient's skin, is shown in FIG. 8. Dispensing gaps 840 are also shown in FIG. 8, whereby these gaps 840 allow the liquid, cream or gel substance 720 in the chamber 710 to gradually come out of the chamber 710 and thereby be applied to the patient's skin by way of the roller 740.

In a sixth embodiment of the invention, an apparatus for enhancing absorption of the skin i