Method and apparatus for cutaneous absorption enhancement and percutaneous drug delivery

Cross-reference to related patent applications This application claims the priority of US Patent Provisional Application No. 60 / 281,808 filed on April 6, 2001, and therefore this application was filed on May 30, 2003. Is a partial continuation application of US Patent Application No. 10 / 448,468 filed in, which is also a partial continuation application of US Patent Application No. 10 / 397,533 filed on March 27, 2003. A partial continuation of US Patent Application No. 10 / 201,644 filed on July 24, 2002, which is also a partial continuation of US Patent Application No. 10 / 074,234 filed on February 14, 2002. It is also a partial continuation application of U.S. Patent Application No. 09 / 942,044 filed on August 30, 2001, and it is also a U.S. Patent Application No. 09 / filed on August 7, 2001. It is a partial continuation application of No. 922,927, each of which is fully incorporated by reference.

The present invention relates to applying electrical pulses and mechanical vibrations to the skin in a controlled manner and at the same time increasing the absorption of the substance applied to the skin, wherein the substance is ascorbic acid, lidocaine, collagen, or the like. Type of skin treatment substance.

The application of electrical pulses to the skin is known to be useful for increasing the absorption of substances previously applied to the skin, a technique called electroporation. Such substances that will be applied to the skin can be, for example, liquids, gels, lotions, or creams.

Providing devices and methods for increasing the absorption of substances that will be applied to the skin, as well as gaining an increased (eg, moisturizing) effect of the substances that will be applied to the skin. Desirable to obtain very even absorption of the substance into the skin.

<p> The present invention is directed to devices and methods for enhancing the absorption of substances that will be applied to the skin.</p>

<p> To achieve this, the present invention provides an electrical pulse train (preferably peak-peak values between 5 and 200 V, preferably frequencies between 50 and 15,000 Hz) provided to electrodes placed in contact with the skin. Between). The application of mechanical vibrations to the skin also provides surface vibrations to the corresponding skin. This mechanical vibration is provided via a vibrating plate, which also includes electrodes, which provide electrical stimulation to the skin at the same time that the mechanical vibration is provided to the skin.</p><p> The substance to be absorbed by the skin is applied to the skin by a probe or syringe. The syringe drains material through a tube, one end of which is connected to the outlet of the syringe, and the other end of the tube is a groove (or trough) that surrounds the center electrode of the array of electrodes. It is placed adjacent to. This type of skin-supplied substance can be a cream, liquid, or gel (eg, collagen, cocoa butter, tanning oil, or other types of skin-enhancing lotions), or a drug that should be administered to the skin. can do.</p><p> Methods according to one embodiment of the invention include: (1) the device is a probe having an array of electrodes at the head portion of the probe and the center electrode is the head portion. A probe that is located at the center of the probe and has multiple peripheral electrodes around the center electrode; (b) a pulse generator connected to an array of electrodes; (c) electrodes on the head portion of the probe. A vibrator that vibrates the head portion of the probe at the same time as an electrical pulse is provided to the array of electrodes; (d) A syringe that delivers the substance to the skin under the control of a motor that ejects the substance from the syringe in a controlled manner so that the substance is delivered to the groove or trough that surrounds the center electrode; To give treatment. During operation, it provides an electrical pulse to the skin through the electrodes on the head of the probe and at the same time provides mechanical vibration to the skin through the vibrating head portion, in which it surrounds the center electrode. The substances distributed in the trough are applied to the skin. The substance is absorbed into the skin due to the perforation of the skin as a result of the simultaneous application of electrical pulses and mechanical vibrations to the skin. Other means provide only electrical pulses to the skin, but do not provide as good a skin absorption effect as when both electrical pulses and mechanical vibrations are used. A hydrogel pad gauze pad may also be provided (instead of using a syringe) on the top surface of the plate on which the electrodes are placed, in which the gauze pad is applied to the patient's skin. Inhale a specific solution.</p><p> The advantages and features of the present invention shown above will be clarified by referring to the following detailed description and the accompanying drawings.</p>

Next, preferred embodiments of the present invention will be considered with reference to the accompanying drawings.

Based on experimental tests on the skin, the inventor has found that pore dilation (or or) within the area between these two points on the skin after one or more pulses are applied between the two points on the skin. Absorption) was found to increase. The pulse that gives the best result is an exponential pulse generated by a charged capacitor that is discharged at at least two distant points on the skin.

These experimental results have shown that the skin can easily apply gels, liquids, lotions, creams, or drugs that are applied to the skin by developing devices and methods that maintain high levels of skin pore dilation. Used by the inventor to allow absorption. The drug can be used, for example, to treat melanoma of the skin and / or cancer cells just below the surface of the skin.

A device according to an embodiment of the invention applies a pulse train across an area or skin by using an array of electrodes that are placed in contact with the skin. The array of electrodes is mounted on a vibrating plate at the head of a probe such as the hand-held probe 500 shown in FIG. This array of electrodes can be configured as shown in FIG. 2A in the first embodiment, in which the odd row of electrodes are electrically connected to each other and the pulse generator 400 (FIG. 4). It is also connected to the first output of) via the first electrical connection. The even rows of electrodes are also electrically connected to each other and are connected to the second output of the pulse generator 400 via a second electrical connection. Alternatively, an array of electrodes on the vibrating plate can be configured as shown in FIG. 2B in a second embodiment, in which odd rows of circular electrodes are electrically connected to each other. , Connected to the first output of the pulse generator 400 via a first electrical connection. Even rows of circular electrodes are also electrically connected to each other and are connected to the second output of the pulse generator 400 via a second electrical connection.

The increase in skin pore dilation obtained by the methods of the invention is a liquid, cream, lotion, gel, or other skin therapeutic agent (or other) previously provided on the skin within the area between the electrodes applied to the skin. It has the effect of increasing the absorption of (kind of drugs).

The electrical pulse applied on the skin to enhance the pore dilation of the skin is the pulse acquired by the discharge of the capacitor on the skin. In other words, the skin acts as a capacitive load when the probe is applied to the skin. The square wave pulse input to the primary winding of the transformer 410 in Figure 4 provides the same effect as a discharge capacitor, with the output of the secondary winding of the transformer 410 being coupled to the skin through the electrodes. To do. However, by using a transformer 410 instead of a capacitor, an electrical pulse applied to the skin so that the amount of current applied to the skin during skin treatment does not exceed a predetermined maximum current value. It is possible to get control of the current with respect to.

Exponential pulses are generated between the rising and falling edges of each square wave input pulse input from the square wave pulse generator to the transformer 410 and have opposite signs (the rising edge of the square wave input pulse). Positive exponential pulses due to the edges, and negative exponential pulses due to the falling edges of the square wave input pulse). By using this type of pulse generator 400, as shown in FIG. 4, adjacent pulses apply a burst of separated pulses with opposite polarities (eg, 500 to 1500 per second) to the skin. It is possible to provide a better pore dilation effect than if it simply provided a single pulse to the skin, or many pulses of the same polarity.

Also, by outputting a burst of pulses to the skin, each burst of pulses containing adjacent pulses of opposite polarity (eg, +-+-+-+-+-...) within the same burst. Any possible current accumulation within is prevented due to the offsetting effect caused by the use of adjacent pulses of opposite polarity. This is in contrast to conventional devices that output electrical pulses of the same polarity, which can result in the accumulation of electrical current in the patient's skin, which has the detrimental effect on the skin as a result of the accumulation of electrical current. It can lead.

As mentioned above, the burst pulse generator uses an inductive element (eg, a transformer) instead of a capacitor to allow control of the current that will be applied to the patient's skin. In conventional devices that use capacitors for electrical pulse generators, when the capacitor is coupled to the patient's skin, the resulting circuit is the first capacitor (the capacitor of the pulse generator) and the second parallel to it. Capacitors (capacitors due to the capacitive / resistant effect of the skin acting as a load). When the voltage is applied to the skin as an electrical pulse, the discharge of the voltage from the first capacitor to the second capacitor results in a very large current spike over the first short period of time, which is easily achieved. I can't control it. As a result, the negative effects caused by large current spikes can be exerted on the patient's skin. As shown in Figure 4, when an inducible element (eg, a transformer) is used in the pulse generator instead of the capacitive element, when a probe with an electrode that provides an electrical pulse is attached to the patient's skin. No current spikes are introduced (because the "capacitive skin" smoothly receives current and voltage from the "inductive pulse generator").

The switching transistor 430 provides a square wave pulse, as shown in FIG. 4A, to the primary winding of the transformer 410, as shown in FIG. The pulses generated by the pulse generator 400 in FIG. 4 are of inversely symmetric polarity as shown in FIG. 4B if the load is pure resistance (or inductive or other type of reactance load). It becomes an exponential decay pulse train. This type of circuit, including the pulse generator 400, provides excellent coupling with the impedance of the skin. Further, in addition to the current control described above, the inductance of the transformer 410, together with the capacitance of the skin, constitutes a resonant circuit, which is desirable to achieve the opening of the skin pores or membrane tissue.

The voltage waveform is conveniently modified due to the fact that when applied to the skin, the electrical equivalent circuit of the skin is equal to the parallelism of resistance and capacitance. The resulting voltage waveform has a longer rise time (due to the RC time constant) and maintains the same peak current and the same exponential decay waveform, depending on the capacitance of the skin.

This type of circuit according to the first embodiment provides advantages over traditional pulse generators that deliver pulses in the form of pre-defined values as well as voltage or current. According to the method according to the first embodiment, it is possible to deliver a higher energy value per pulse, and at the same time avoid possible damage to the skin that occurs when a high current amount is applied to the skin. It is possible. The circuit used in the first embodiment self-adjusts the current, voltage, and waveform shape values. In particular, the impedance of the skin decreases after the first pulse is applied to the skin. Thus, the voltage of the first pulse is higher than that of the subsequent pulse because the impedance of the skin at the time the first pulse is applied to the skin is higher. The voltage of the second and subsequent pulses applied to the skin decreases with decreasing skin impedance, but the peak current remains the same or nearly the same.

Typical current and voltage values are shown below. Case 1: 10 kiloohm load impedance, 100V peak voltage, 10mA peak current, 220 microsecond pulse width. Case 2: 1 kiloohm load impedance, 10V peak voltage, 10mA peak current, 220 microsecond pulse width. These pulses are preferably delivered within the burst, where the burst rate is the same as or about the same as the mechanical vibration rate. Typical values for the burst rate (and mechanical vibration rate) are between 40Hz and 100Hz.

The inventor of the present application can use mechanical vibration at the same time as an electric pulse is applied to the skin and at the same or almost the same frequency as the burst rate of the pulse. It was also recognized that it would result in the patient having greater tolerance to pulse intensities (current and voltage). For example, using an electric pulse burst rate of 50 Hz (ie, the rate between bursts of pulses), apply mechanical vibrations in the range between 40 and 60 Hz, and apply an electric pulse burst to the skin. At the same time, it can be provided to provide a "masking effect". The inventor also states that at or near the fundamental frequency of the electrical pulse burst rate (eg, +/- 10% of it), at or near the first tuning of the electrical pulse burst rate, the electrical pulse burst. The use of mechanical vibration in or near the second tune of the rate and / or in or near the third tune of the electrical pulse burst rate gives the patient a "pleasant sensation" and, as a result, They have also found that patients can withstand higher intensity electrical pulses applied to their skin at the same time. Therefore, when it comes to electrical pulse burst rates of 50Hz, mechanical vibrations with any mechanical vibration rate of 40 to 60Hz, 90 to 110Hz, 140 to 160Hz, and / or 190 to 210Hz. It may be applied to the patient's skin at the same time. Applying a mechanical vibration to the patient's skin at the same time as applying the electrical pulse burst to the patient's skin reduces the patient's level of discomfort caused by the spicy sensation of the electrical pulse (eg, somewhat masked).

Normally, when a square wave is applied to the skin, it is possible to obtain an exponential decay current with a time constant of about 3 microseconds due to the capacitive effect of the skin. This occurs when a square wave voltage is applied to the circuit corresponding to the parallel of the resistor and the capacitor.

With this type of circuit, by applying electrical energy equal to the magnetic energy of the transformer 410, only the peak current is increased and the skin is charged to the maximum permissible voltage. This effect is most likely to provide the opening of cell membranes or skin pores over the period of time each pulse is applied to the skin (the pore dilation effect is likely to be achieved).

The effect of applying the probe to the skin is that the skin vibrates due to the electrical pulses applied by the array of electrodes. Electrical pulses are preferably applied at a fixed frequency between 200 and 10,000 Hz (optimally a frequency between 2,500 and 3,000 Hz) and grouped into bursts of pulses (eg, each burst is 100). Corresponds to 1000 individual pulses from, each of which has opposite polarity with respect to adjacent pulses within the burst of the same pulse). The on-time for each burst has a fixed value between 5 and 50 ms, and the off time between two consecutive bursts has a fixed value between 5 and 50 ms (preferred bursts. The on-time is 10 ms, and the preferred burst-off time between consecutive bursts is 10 ms).

As mentioned above, the electrical pulse applied to the skin through the electrodes is preferably an exponential pulse with a peak-peak voltage of 160 V and a frequency fixed at either 2,500 to 3,000 Hz. One way to provide this kind of electrical pulse is to use the electrical structure corresponding to the pulse generator 400 as shown in FIG. 4, in which the transformer 410 is used as an element of the pulse generator 400. Is used.

Other elements of the pulse generator 400, including the transformer 410, are preferably housed in the probe 500 shown in FIG.

Returning to FIG. 4, the primary winding 420 of the transformer 410 is driven by a transistor 430 that switches on and off, and the secondary winding 440 of the transformer 410 is directly coupled to the array of electrodes (see Figure 1A or 1B). , An electrical resistance 450 is provided between them. The electrical resistance 450 is a value within 200 kiloohms or within a predetermined range (eg, 100 kiloohms to 500 kiloohms), and the array of electrodes is not applied to the skin, which results in an open circuit. It is provided to avoid high voltage when it will be done. In such situations, the peak-peak voltage will be at or near 400V.

Along with the electrical pulse applied to the skin, in the first embodiment, mechanical vibration is also applied to the skin to increase the absorption of the substance applied onto the skin.

The absorption effect is enhanced by the simultaneous increase in pore expansion, in which the absorption effect is maximized when the mechanical vibrations are synchronized with the application of electrical pulses in phase and frequency. Thus, in the example described above, the vibrating plate also causes the skin to be subjected to a burst of electrical pulses (2,200 Hz) through an array of electrodes, for example at a burst on / off frequency of 50 Hz. It is mechanically oscillated at the same frequency, for example 50Hz. The application of this mechanical vibration and electrical pulse is preferably provided in phase with each other in order to increase the absorption effect of the skin. There are several well-known methods for achieving this frequency and phase synchronization. In the preferred embodiment described herein, the motion of the eccentric ring of a motor used to provide mechanical vibration (see, eg, FIGS. 1A and 1B) is detected by an optical sensor (not shown). It gates a burst of electrical pulses based on the detected motion.

Thus, in the example described above, the skin is mechanically vibrated at the same frequency through the vibrating plate while a burst of electrical pulses is applied to the skin through the array of electrodes. This mechanical vibration and application of electrical pulses are preferably provided in phase with each other in order to increase the absorption effect of the skin.

In addition, the absorption effect is further increased when mechanical vibrations are applied perpendicular to the surface of the skin. Applicants are not intended to be limited to any particular theory of motion, but one possible description of a physical phenomenon in one or more embodiments of the invention is that electrical pulses apply to the skin. "Stretching", resulting in a periodic increase in the diameter of the pores in the skin, while at the same time mechanical vibrations "push" a substance (gel, liquid, or cream) into the skin (through the open pores). ]. The synchronization of mechanical and electrical stimuli has a "feeding" effect (due to mechanical stimuli to the skin) at the same moment the holes are at maximum "open" diameter (due to electrical stimuli to the skin). Achieve the effect that occurs.

A device according to the first embodiment of the present invention includes a probe having two main parts shown below: (A) a handle containing a power source (eg, a battery) and a pulse generator; and (B) vibration. A vibrating head that contains components to generate and also contains an array of electrodes.

In a preferred configuration of the first embodiment, the vibration head comprises a DC electric motor for generating vibrations against the skin. FIGS. 1A and 1B show the DC electric motor 110 from two different directions, where the rotating shaft of the DC electric motor 110 is an eccentric ring 120 that provides eccentric motion. This eccentric motion is on the vibrating plate 130 (which is directly coupled to the DC electric motor 110) during the rotation of the DC electric motor 110 at the same frequency as the rotation of the DC electric motor 110 (eg 50Hz or 60Hz or otherwise). Generates vibrations of the desired frequency). Other methods of producing vibrations synchronized with the provision of electrical pulses are also conceivable, but ultimately fall within the scope of the present invention. It should be noted that, as mentioned above, the use of mechanical pulses that are the same as or substantially the same as the burst rate of the electrical pulses, but do not require synchronization with each other, results in the use of mechanical pulses that are brought about by receiving only electrical pulses to the skin. It is to provide a positive effect in reducing the patient's discomfort level associated with a tingling sensation. Also, the use of adjacent pulses of opposite polarity within each burst does not result in any accumulation of current on the patient's skin, but the use of identically polar electrical pulses, which are given to the patient's skin. In conventional devices, it can be a detrimental effect.

As already described, FIG. 4 shows a circuit for providing electrical pulses to the array of electrodes shown in FIGS. 2A and 2B. The circuit of FIG. 4 corresponds to the pulse generator 400 and is preferably located within the housing of the probe 500 of FIG. The electrical pulses generated by the pulse generator 400 are exponential pulses, preferably with a peak-peak voltage of 160 V and a frequency between 2,500 Hz and 3,000 Hz, when those pulses are applied to the skin. Of course, other peak-peak voltages (eg 100V to 200V) and operating frequencies (50Hz to 15,000Hz) may be employed, but ultimately within the scope of the invention as described herein. Return. Alternatively, sawtooth or sinusoidal pulses may be provided to the electrodes, but exponential pulses are expected to provide better skin pore dilation results.

Figures 1A and 1B show the vibrating plate 130 physically coupled to the DC electric motor 110. The vibrating plate 130 is preferably of a size of 50 x 50 mm (other sizes are possible but ultimately fall within the scope of the present invention), and as shown in FIG. 2A, there are electrodes on it. Parallel metal strips are arranged to form an array of. The vibrating plate 130 is vibrated in the same phase and frequency as the electrical pulses provided to the skin via an array of electrodes (placed on the vibrating plate) to enhance the absorption effect of the skin.

FIG. 2A shows a first embodiment of the electrode array 210 provided on the skin side surface of the vibrating plate 130, each preferably having a size of 50 mm × 4 mm 5 as shown. A parallel metal strip 220 of the book is provided. A distance of preferably 6 mm is provided between each of the five electrodes 220 from the adjacently arranged electrodes. The electrodes 220 are alternately electrically connected (eg, rows 1, 3, and 5 are electrically connected to each other by electrical lines 250, with rows 2 and 4 being electrically connected. , Electrically connected to each other by electrical lines 260). Other electrode array configurations with more than 2 electrodes, such as having 7 or 8 electrodes, are possible, but ultimately fall within the scope of the present invention.

FIG. 2B shows a second embodiment of the electrode array provided on the skin side surface of the vibrating plate. In FIG. 2B, there are 25 circular electrodes 230, each with a diameter of 4 mm, each spaced at least 6 mm from the adjacent circular electrodes. These circular electrodes 230 are alternately electrically connected to each other (for example, the electrodes in the first, third, and fifth rows are electrically connected to each other by an electric line 270, and the second row. The electrodes in rows and 4 are electrically connected to each other by an electrical line 280). The spacing between the circular electrodes 230 shown in FIG. 2B can vary from 1 to 20 mm, and the size of the circular electrodes 230 can vary from 1 to 20 mm in diameter.

FIG. 2C shows an array of electrodes mounted on the skin-facing outer surface of a vibrating plate according to a third embodiment of the invention. In Figure 2C, electrodes 233 located on the periphery of the vibrating plate are shown, which are electrically coupled to each other and further to the first output of the pulse generator 400 via the first electrical connection 235. To be combined. Figure 2C also shows a centered electrode 237, which of the pulse generator 400 via a second electrical connection 239, without being electrically coupled to any of the other electrodes. It is electrically coupled to the second output.

FIG. 3 shows a vibrating head 310 of a probe used according to an embodiment of the present invention that provides both electrical and mechanical stimulation to the skin for better absorption of pre-applied material. It is a side view. As shown in FIG. 3, the vibrating head 310 includes an electrode array 320 provided on its surface on the skin side. The electrode array 320 can be provided, for example, in the manner shown in either FIG. 2A or 2B. Between the electrode array 320 and the skin 330, a substance 340 to be absorbed is provided, in which the substance 340 is previously applied to the skin 330 (eg, 30 before the probe is applied to the skin 330). It is applied to the skin between seconds and 2 minutes). The application of mechanical vibrations and electrical pulses enhances the absorption of substance 340 into the skin 330.

FIG. 5 shows one configuration of a hand-held probe 500 that can be used to apply both electrical and mechanical stimuli to the skin according to one or more embodiments of the invention. The probe 500 is configured so that the user can easily hold it with one hand. The bottom portion of the probe 500, which the user holds in his hand to hold the probe 500, may include an outlet 510 for connecting an electrical cable to an electrical outlet (eg, a wall outlet) and supplying AC voltage to the probe 500. it can. Alternatively, battery power can be used via a battery (not shown) located within the housing of the probe 500. Battery power can be used when AC power is not readily available. The pulse generator 400 of FIG. 4 is preferably housed in the handle portion of the probe 500.

The head portion of the probe 500 is the portion provided with the vibrating plate 130 (see FIG. 1A or 1B), and the DC electric motor 110 (also see FIG. 1A or 1B) that provides mechanical vibration to the vibrating plate 130 is preferred. Is also the part that is housed. An array of electrodes (see FIG. 2A or 2B) is provided on the outer surface of the vibrating plate 130, thus facing the user's skin to be treated by probe 500.

The general time for applying the probe to the skin can range from tens of seconds to minutes.

In a fourth embodiment, as shown in FIG. 6, the output of the pulse generator 400 (see FIG. 4) is connected to the DC current generator 610, which, in addition to the skin absorption / pore dilation effect described above. Induces the iontophoresis effect. The iontophoresis effect is well known to those of skill in the art, and there are several iontophoresis electric generators currently on the market, either DC or pulsed DC. The DC output from the DC current generator 610 is applied between the electrodes of the probe and the ground plate connected to the patient's body. Depending on the substance to be absorbed into the patient's skin, the patient ground plate connection is coupled with either the positive or negative of the DC current generator 610 in a manner well known to those of skill in the art. Instead of using continuous DC current, a DC current pulse with a duty cycle between 5 and 50% and a frequency between 10 and 5000 Hz, with an average current value equal to that for continuous DC current. It is also possible to provide. In such cases, the peak current of the DC current pulse becomes higher over the time it is pulsed (on).

In a fifth embodiment, as shown in FIGS. 7 and 8, a dispenser or chamber 710 configured to hold the cream or gel 720 is incorporated within the vibrating head of the probe. A dispenser or chamber 710 is provided between the electrode array 705 and the vibrating plate 130. A burst of electrical pulses is applied by a conductor roller 740 and an electrode array 705 that apply the liquid. As in the third embodiment, a DC current can be added between the electrode array 705 and the patient's body to further induce an iontophoresis effect. When the vibrating head is moved over the patient's skin, the roller 740 applies a liquid or cream or gel 720 to the patient's skin.

The chamber 710 in which the rollers 740 are located in the vibrating head is filled with liquid, cream or gel material 720 via a removable cap (not shown). More specifically, the user removes this cap (eg, turns it in the direction to open the cap to remove it from the probe head) and chambers 720 substance 720, which will be delivered to the patient's skin through the liquid spout 760. Fill in. The user then closes the cap (eg, turns the cap in the closing direction and tightens it again into the liquid spout 760), thereby the probe chamber until the substance 720 is ready to be applied to the patient's skin by the roller 740. Keep it in the 710.

FIG. 8 shows a front view of the electrode 705, in which the electrodes are shown as bands of two electrodes electrically connected to each other by an electrical connection 820. Of course, instead, other types of electrode arrays, such as those shown in FIGS. 2A and 2B, can also be used in this fifth embodiment. Referring to FIG. 8, the exposed surface 830 of the roller 740, which applies the substance to the patient's skin, is shown. The application gap 840 is also shown in FIG. 8, which allows the liquid, cream or gel material 720 in the chamber 710 to gradually exit the chamber 710, resulting in the roller 740. Allows it to be applied to the patient's skin.

In a sixth embodiment of the invention, a device for enhancing skin absorption comprises an array of electrodes and a pulse generator that is electrically coupled to the array of electrodes. For the arrangement of the array of electrodes, for example, any of the arrangements shown in FIGS. 2A to 2C may be used. In a preferred embodiment of the sixth embodiment, the electrical pulse output from the pulse generator 400 towards the array of electrodes becomes an exponential pulse train such as the pulse train shown in FIG. 4B. Exponential electrical pulses are applied to the skin through an array of electrodes and, as shown in Figures 4, 4A, 4B, the secondary winding of a high voltage transformer with a primary winding driven by a square wave voltage. Is generated by.

In this sixth embodiment, unlike previous embodiments, no vibrating head is used and increased skin absorption is obtained only by providing electrical pulses to the skin through an array of electrodes. An array of electrodes according to the sixth embodiment is provided on a plate at the head of the probe, in which the head as well as the plate do not vibrate. Thus, in the sixth embodiment, the structure as shown in FIGS. 1A and 1B is not used, but only the plate is needed to hold the electrode in the proper position of the probe head.

In the seventh embodiment, the vibrating head is used as in the first to fifth embodiments, but the vibrating head can be turned on or off by a control (for example, a switch) provided on the probe. Is. This control can be easily manipulated by the probe operator to treat the patient.

Next, an eighth embodiment of the present invention will be described with reference to FIGS. 9 to 11. FIG. 9 shows a front view of the probe head 800, in which the portion of the probe that is applied to the patient's skin is shown. FIG. 10 is a cross-sectional view cut along one belt axis, and FIG. 11 is a cross-sectional view cut along the center of the probe head.

Eighth embodiment provides very uniform subcutaneous absorption of a substance pre-applied to the skin, such as collagen pre-applied to the skin. In an eighth embodiment, the probe head 800 applied to the skin includes a vibrating plate 810, a vacuum chamber 820, a roller 830, and a belt 840 placed around the roller 830. The roller 830 is a conductor roller in which the roller 830 is electrically coupled to electrodes provided on the vibrating plate 810 (see, eg, FIGS. 2A-2C). As in other embodiments, a pulse generator (see, eg, FIG. 4) with electrodes on the vibrating plate 810 to deliver electrical pulses (via conductor rollers) to the patient's skin. It is electrically coupled.

In the eighth embodiment, the rollers 830 are separated from each other by about 40 mm. Of course, other separation distances are possible, but ultimately fall within the scope of the present invention (eg, 20mm-80mm separation). The roller 830 is located at one end of the vacuum chamber 820, in which the vacuum chamber 820 has an opening through which the pipe 845 is coupled and which is further coupled to the vacuum pump 855.

When the vacuum pump 855 is activated, the vacuum chamber 820 provides a suction effect on the skin 850, which allows for stronger contact between the rollers 830 and the skin 850, which is further produced by the vibrating plate 810. In addition to the vibrating vibration, an additional massage effect on the skin 850 is created. Belts 840 are provided on both ends of the roller 830, preferably rubber belts. Belt 840 is used to avoid direct friction between the skin 850 and the body of the vacuum chamber 820.

This eighth embodiment provides good skin absorption results and reduces cellulite in the skin after application of a substance to reduce cellulite to the skin. A substance for reducing cellulite that can be applied to this type of skin can be, for example, jalulon acid. This type of substance can be pre-spread on the skin and absorbed by the skin using one of the embodiments described above.

Further, the eighth embodiment is described as having a vibrating plate as in the first to fifth embodiments, but in the alternative configuration, the sixth embodiment and (the vibrating plate is A non-vibrating plate can be used as in the seventh embodiment (when off). In that case, the plate placed above the vacuum chamber is non-vibrating, but the electrodes placed there are included.

Next, the ninth embodiment will be described in detail with reference to FIGS. 12 to 14. A ninth embodiment is a motor 1, a screw 2, a slide 3, a frame 4, a piston 5, a syringe 6, a pipe (or tube) 7, and a center electrode 8 and a peripheral electrode 9 on the head 10 (outside the center electrode 8). Is located in). The head 10 is a head portion of the probe, eg, the head of the probe shown in FIG. 5 of the above embodiment (in the fifth embodiment, material is contained in a chamber in the head adjacent to the electrode plate. The exception is that it will be contained, in which case the syringe will not be needed).

In this ninth embodiment, the syringe 6 is preferably a disposable single-use syringe, located adjacent to the probe (FIG. 12 shows only the probe head 10). The rest of the probe is hidden behind the head 10 in the figure provided in Figure 12). The syringe 6 is inserted or fitted into the frame 4 and does not move relative to the frame 4. For example, the frame 4 can be placed on a table adjacent to the bed where the patient to be treated is located.

The piston 5 is movable relative to the frame 4, in which the movement is provided by the motor 1, the screw 2, and the slide 3, which act as a unified means of transportation. Using the configuration shown in FIG. 12, the probe is self-supporting and relative to the frame 4 (while maintaining the bond with the syringe 6 via the tube 7 that connects the syringe 6 with the probe head 10). It is possible to make a predetermined amount of movement (eg, 1-10 feet, depending on the length of the tube 7). That is, the probe can be moved with the frame containing the syringe 6 placed on a table adjacent to the bed to treat different areas of the patient's skin lying on the bed. In the alternative configuration, both the probe and the syringe 6 can be mounted on the frame 4 as a single block configuration. In that configuration, the entire frame can be moved to different areas of the patient's skin and the patient treated via a probe inserted within the frame. The probe head extends outward from one end of the frame so that it can be placed against the patient's skin.

In a preferred embodiment, the motor 1 is powered by a different power source than the one supplied to the probe. However, in another embodiment, the motor 1 and the probe are powered by the same power source.

The pipe or tube 7 is used to connect the syringe 6 to the probe head 10. The tube 7 is preferably a disposable single-use component, for example a flexible plastic tube. The head 10 is preferably a vibrating head as described above for other embodiments. In the alternative configuration, the head 10 does not vibrate and in that alternative configuration only electrical pulses are provided to the skin (thus electroporation of the skin takes place and the skin via syringe 6 and tube 7). The substance provided to is absorbed). The tube 7 is preferably 0.5 to 3 millimeters in diameter, and a second, opposite the first end of the tube 7, where a liquid or creamy substance flows through the tube 7 and is combined with the syringe 6. It is sized to drain it from pipe 7 at the end of the pipe. This type of substance applied to the skin can include many such as aqueous collagen, aqueous elastine, and other types of agents.

As shown in FIG. 14, the tube 7 and the head 10 are connected by a groove 12 which is arranged at the end of the head 10 and is provided between the groove 11 and the groove 11 which surrounds the center electrode 8. To. The groove 12 is sized to accommodate the tube 7 and provide a sliding fit, in which the tube 7 preferably inserts the tube 7 into the groove 12 from the end of the head 10 where one end of the groove 12 is located. It is fitted into the groove 12 by feeding. In this ninth embodiment, the tube 7 does not reach over the upper surface of the head 10 (the surface on which the electrodes 8 and 9 are located), or the tube 7 is on the upper surface (plate) of the head 10. Groove 12 is sized to reach just below. That is, the patient does not perceive tube 7 when moving the probe head 10 along the patient's skin during treatment. Preferably, the tube 7 does not come into contact with the patient's skin during treatment of the patient via the method and / or device according to the ninth embodiment. The top surface of the head 10 preferably has a plate-like structure to provide a smooth sensation to the patient's skin.

On the top surface of the head 10, one center electrode 8 and a plurality of peripheral electrodes 9 arranged around the center electrode 8 are provided. The groove or trough 11 surrounding the center electrode 8 is preferably 1 mm wide, in which the groove 11 is coupled to one end of the groove 12 in which a portion of the tube 7 is located. That is, when material is delivered from syringe 6 (via the movement of motor 1, screw 2, and slide 3), the material flows through tube 7 (located in groove 12), thereby. It flows into groove 11. The material collects in the groove 11 surrounding the center electrode 8 and is absorbed by the skin during electroporation treatment (using electrical pulses and mechanical vibrations) via the ninth embodiment. To. When the top surface (plate) of the head 10 comes into contact with the patient's skin, the material in the groove 11 comes into contact with the patient's skin and is absorbed by that skin.

Although eight peripheral electrodes 9 are shown in FIG. 12, the invention according to a ninth embodiment can operate with a different number of peripheral electrodes 9. For example, in different configurations, a minimum of two peripheral electrodes 9 can be used that are located opposite each other (with a center electrode 8 between them). Also, in another different configuration of the ninth embodiment, four peripheral electrodes 9 are used, or more than eight peripheral electrodes 9 (eg, 16 electrodes surrounding the center electrode 8). , 32 electrodes, or an odd number of peripheral electrodes such as 3, 5, or 7) can also be used.

An electrical pulse can be delivered to electrodes 8 and 9 located on the probe head 10 using a pulse generator as shown in Figure 4 (see also Figures 4A and 4B). it can. As described above, the preferred shape of the electric pulse is an exponential shape as shown in FIG. 4B. Alternatively, a sinusoidal or sawtooth wave may be supplied, but exponential pulses provide a better skin pore dilation effect. The operation of the pulse generator that can be used in the ninth embodiment has been described in detail in relation to the first embodiment described above, and for the sake of brevity, it will not be repeated here.

One of the two outputs of the pulse generator (see Figure 4) is connected to the center electrode 8 and the other of the two outputs of the pulse generator is connected to one of the peripheral electrodes 9. The peripheral electrodes 9 are electrically coupled to each other on the back side of the head (see dashed line in Figure 2C), resulting in the electrical pulse delivered over the other of the two outputs of the pulse generator. Each is supplied simultaneously to all of the peripheral electrodes 9.

The voltage of the electrical pulse provided to the skin from each of the eight peripheral electrodes 9 can be thought of as the "ground" for the voltage of the electrical pulse delivered to the skin from one center electrode 8. Since the center electrode 8 carries more current than each of the eight peripheral electrodes 9, the peripheral electrode 9 acts like a ground connection, in which the current carried by each of the eight peripheral electrodes 9 is the center electrode. It is about one-eighth of the current carried by 8.

The piston 5 of the syringe 6 is driven by a motor 1 which, in a preferred embodiment, is a DC electric motor. The motor 1 is connected to a screw 2, which moves the piston 5 at a specific position on the screw 2 via a slide 3 attached to the screw 2. When the probe head 10 is placed on the patient's skin, an electrical pulse is delivered to the electrodes 8 and 9, and the piston 5 of the syringe 6 transfers a liquid or creamy substance (or drug) from within the syringe 6 to the patient's skin. Moved by motor 1 to deliver to. The liquid, cream, or drug is preferably delivered to the patient's skin in a slow and controlled manner, allowing the substances to be properly absorbed into the skin. For example, via a method or device according to a ninth embodiment, aqueous collagen, aqueous elastine, an anesthetic, or other type of drug is fed into syringe 6 and then the patient's skin (which should be absorbed). Can be supplied to.

In the ninth embodiment, the improvement of skin absorption by the application of an electric pulse to the skin and the simultaneous application of mechanical vibration to the skin in synchronization with it (see the description of the vibration plate for other embodiments). Allows absorption of the drug or other type of substance delivered by the syringe 6. A typical drug absorption is 1 cubic centimeter per 1-5 minutes and the method and device according to the ninth embodiment is used. In this regard, the movement of the piston 5 is timed to expel the correct amount of material from the syringe 6 during the treatment of the patient, in which the event when the probe is turned on, A trigger signal for starting the operation will be provided to the motor 1. Subsequently, the operation of the motor 1 pushes the substance in the syringe 6 from the syringe 6 into the groove 12 surrounding the center electrode 8.

The material has been pre-loaded into the syringe, so that the material-supplied syringe 6 is attached to the frame 4 and the tube 7 is joined to form an electrode on the head 10, i.e. the outer surface of the plate. A device is provided capable of directing a drug and / or other substance to the patient's skin using a probe with a head 10 with 8, 9. As described above, the head 10 vibrates, resulting in both electrical and mechanical vibrations being delivered to the patient's skin, while at the same time the drug or other substance is delivered to the patient's skin (patient during patient treatment). Provided (as a substance distributed within a trough or groove 12 that comes into contact with the skin of the patient). Although not as good as using both mechanical vibrations and electrical pulses, in alternative configurations that provide a pore-dilating effect on the skin, only electrical pulses are delivered to the patient's skin (head does not vibrate). This configuration is cheaper to make and may be appropriate in some cases.

Motor 1, screw 2, slide 3, piston 5, syringe 6, frame 4, and tube 7 combine different types of probes to provide equipment for enhancing skin absorption and for transdermal drug administration. be able to. For example, any probe described for other embodiments (except for the embodiment in which the material is stored in a container within the head of the probe) may be used with the above components. Further, the structure for discharging the substance from the syringe 6 can be achieved by a method other than the transportation means of the screw / slide / motor / described in connection with FIG. 12, but in the end, the scope of the present invention. Return to.

FIG. 13 shows the back of the head 10, which is used to provide components used to connect electrodes 8 and 9 to the head and electrical connections to electrodes 8 and 9. Components are also shown. The motor 1310 is used to provide mechanical vibrations to the head 10 including the eccentric ring 1320 coupled to the output of the motor 1310, so that the device produces both electrical and mechanical vibrations. At the same time, it is provided to the patient's skin. Mechanical vibrations are preferably synchronized with electrical pulses, as described for other described embodiments of the present invention.

Electrodes 8 and 9 are preferably screwed onto the face plate of the head 10. Washers 1330 and screws 1340 are used to electrically couple wires 1350, 1355 with electrodes 8 and 9. In particular, the wire 1350 (one end coupled to one of the two outputs of the pulse generator, eg, as shown in FIG. 4) is electrically connected to the center electrode 9 and the wire 1355 (one end, eg, is coupled). (Coupled to the other of the two outputs of the pulse generator, as shown in FIG. 4) is electrically connected to the peripheral electrode 8. In a preferred configuration, resistor 1365 is inserted between wires 1350 and 1355. FIG. 13 also shows housing 1375, which is coupled to head 10 via screw 1380. The eccentric ring 1320 moves within the housing 1375, thereby causing vibrations transmitted to the probe head 10.

Next, a tenth embodiment of the present invention will be described with reference to FIGS. 15 and 16. The tenth embodiment is similar to the ninth embodiment, except that it has a plurality of transformers (see FIGS. 4, 4A, and 4B), including using different configurations for the heads. .. FIG. 15 shows a rear view of the electrode 1500 located on the probe head 1510, and FIG. 16 shows a front (skin side) view of the electrode 1500, in which each electrode is around its own. Has a groove or trough 1530 that surrounds it. Each groove 1530 has an outlet that reaches the edge of the head 1510, which allows the respective tube 1550 to be fitted therein and a predetermined amount of material to be supplied from the syringe 6 to the groove 1530. In that case, tube 1550 does not reach above the top surface of head 1510. As a variant of the multi-port tube configuration shown in FIG. 16, a large number of syringes equal to the number of electrodes can be provided with each syringe and a tube connecting each electrode.

In a tenth embodiment, each electrode 1500 is active and is connected to its own pulse transformers 1560A-1560I, respectively. The material from syringe 6 is fed to the groove 1530 that surrounds each electrode 1500. Electrical pulses are supplied from the respective pulse transformers 1560A to 1560I to the groove 1530, where the transformers 1560C, 1560E, 1560G, and 1560I send positive pulses to the corresponding electrodes in the case of a 9-electrode configuration. At the same time, the transformers 1560A, 1560B, 1560D, 1560F, and 1560H provide negative pulses to their respective electrodes. More specifically, the transformers 1560C, 1560E, 1560G, and 1560I have their primary and secondary windings in-phase coupled, and the transformers 1560A, 1560B, 1560D, 1560F, and 1560H are their primary windings. The windings and secondary windings are coupled with a 180 degree phase difference (see the dots placed on opposite sides for these transformers in Figure 15). When a square wave is applied to the primary windings of all these transformers at the same time, a transformer in which the primary winding and the secondary winding are in-phase coupled to each other when a positive transition from low to high occurs. Will output a positive exponential pulse, and a transformer in which the primary and secondary windings are coupled with each other with a phase difference of 180 degrees will output a negative exponential pulse.

In a tenth embodiment, when the first group of electrodes receives a positive pulse and the second group of electrodes (preferably equal or nearly equal in number to the first group) is a negative pulse. It is preferable that the receiving time is simultaneous in order to provide good skin pore dilation. The pulse type, burst duration, frequency, etc. are similar to the embodiments already described. A tenth embodiment may also include mechanical vibration applied to the patient's skin at the same time as the application of the electrical pulse to the patient's skin, according to the method described above.

In the eleventh embodiment, a plurality of transformers are provided to output electric pulses to a plurality of electrodes arranged in the head portion of the probe, in which the plurality of transformers are sent to the corresponding electrodes. , Provides separate bursts of independent pulses. For example, each pulse generator in the eleventh embodiment can have different phase shift amounts in the range 0 to 360 degrees. In this regard, the output pulses from the transformer are synchronized with each other and have a specific phase shift relationship with respect to each other.

An example of the electrode array according to the eleventh embodiment is shown in FIGS. 17, 18, and 19. This example provides a three-electrode configuration without a center electrode. First refer to FIG. 17, which shows the front side of the head 10, where electrodes 1700 are each coupled to syringe 6 via a tube 1710 and within a groove 1720 that surrounds each electrode 1700. Receive the substance at. Similar to the previous embodiment, as shown in FIG. 14, a groove or path extending to the end of the head 10 is provided for sliding the tube 1710 into it, so that the tube 1710 is It does not reach above the upper surface (plate) of the head 10 that comes into contact with the patient's skin.

Referring here to FIG. 18 showing the back of the head 10, each transformer 1810A, 1810B, and 1810C combined with each transformer a pulse of the same polarity but delayed by a certain amount from each other. Provided to the corresponding one of the electrodes 1700. FIG. 19 shows the input square wave pulse supplied to each transformer, in which the square wave pulse input to the transformer 1810C is a specific amount (eg, for example) with respect to the square wave pulse input to the transformer 1810B. It is delayed by a certain amount (eg, 30 degrees) with respect to the square wave pulse input to the transformer 1810A. This can be easily done by providing the corresponding transformers 1810A, 1810B, and 1810C with a trigger "IN" signal at the right time. As a result, exponential pulses are output from each of the three pulse generators, in which these exponential pulses are phase-shifted by a certain amount with respect to each other.

When using a three-electrode, three-phase generator configuration as shown in Figures 17-19, for the signals output by the three pulse generators, a 120 degree phase shift (eg, one output at 0 degrees). It is possible to provide a signal, one signal output at 120 degrees, and one signal output at 240 degrees). This provides between the electrodes 1700 the rotation of the electric field in a manner similar to that that occurs with the rotation of a three-phase motor. More generally, those skilled in the art will be treated in an eleventh embodiment using an "n" electrode and an "n" pulse generator, via an apparatus according to the eleventh embodiment. It will be appreciated that it is possible to create any particular type of electric field distribution desired on the surface of the skin.

Next, a twelfth embodiment will be described with reference to FIG. In a twelfth embodiment, probe 2010 is used to provide a skin absorbent to the skin. In that regard, the probe 2010 can be a probe according to any of the previous embodiments of the invention already described herein. As shown in FIG. 20, probe 2010 has a vibrating head 2020 and an electrode array 2030 provided at the end of the vibrating head 2020. In a twelfth embodiment, gauze 2033 is provided between the head 2020 of probe 2010 and the patient's skin 2040. Preferably the gauze 2033 is a pad having the same size (or substantially the same size) as or larger than the vibrating head 2020 of the probe 2010 and covers the treatment area where the vibrating head 2020 is expected to be moved. In a preferred embodiment, gauze 2033 is a commercially available pad (eg, thickness 0. It will be a rectangle or square between 1 and 1 mm). With gauze 2033 between probe 2010 and patient skin 2040, probe 2010 does not come into direct contact with patient skin 2040. Gauze 2033 takes into account that the probe 2010 can be easily moved across the patient's skin 2040 with less friction than when gauze 2033 is not used. The inventor has also found that the use of gauze 2033 provides a more homogeneous application of the skin absorbent 2035 to the patient's skin 2040. As an alternative to gauze, other types of pads, such as cotton tissue or synthetic (eg nylon) tissue, may be used between the patient's skin 2040 and probe 2010. All of these pads are from the vibrating head 2020 of the probe 2010 (the container therein) through the pad 2033 (for embodiments in which the skin absorbent 2035 is stored in the head 2020 of the probe 2010) onto the patient's skin 2040. It has sufficient porosity characteristics that allow the skin absorbent 2035 to be delivered to.

An important feature in the present invention according to the twelfth embodiment is that gauze is provided between the head of the probe and the skin of the patient. In one possible embodiment, the gauze is applied to the probe head rather than the patient's skin. In another possible embodiment, the gauze is applied to the patient's skin rather than the probe head. With either embodiment, a more even distribution of skin absorbents to the skin (compared to when gauze is not used) is obtained, while at the same time less (compared to when gauze is not used). Allows the probe head to move (to treat a specific area of the patient's skin) across the patient's skin with friction. In one possible embodiment of the twelfth embodiment, it is possible to apply gauze to the patient's skin in a variety of removable ways, such as using medical tape. In another possible embodiment of the twelfth embodiment, a rubber band is used to fasten the gauze pad to the probe head (the rubber band grips around the side wall of the probe head), or Use adhesive tape to glue the gauze pad margins to the side walls of the probe head, or gauze an outer (eg plastic) sheath that allows the gauze pad to be easily fitted and removed onto the probe head. It is possible to attach gauze to the probe head in a variety of removable ways, such as preparing for a pad. In any of these cases, the gauze can be easily removed from the patient's skin or from the probe head and discarded after use.

With reference to FIGS. 21-24, in the thirteenth embodiment, the skin treatment device is configured to deliver a defined amount of lidocaine, ascorbic acid, or other skin treatment agent into the skin. With the configuration as described for the third embodiment, ie, the center electrode 2110 and the eight peripheral electrodes 2120 arranged around the center electrode, the center electrode 2110 is connected to one output of the pulse transformer and eight. On the head of the probe, where the peripheral electrode 2120 can be configured to connect to the other output of the pulse transformer, the plate 2210 is coupled to the head (see Figures 23 and 24), and the electrodes 2110 and 2120 are of the probe. It is provided between the head 2130 and the patient's skin.

Preferably the plate 2210 is a plastic layer (300 microns thick in a preferred embodiment) and nine holes corresponding to the nine electrodes placed on the head are bored. The plate preferably has a top surface area of 60 mm × 60 mm (electrodes are placed at different points on the top surface area). Two concentric squares 2230, 2240 made of non-conductive rubber are bonded to the top of the plastic layer 2210 (other bonding methods such as taping can be planned, but ultimately fall within the scope of the present invention). .. Each of the concentric squares 2230, 2240 preferably has a width of 5 mm and a thickness of 5 mm. A first (or outer) gauze pad 2260 is fitted between the outer square 2240 and the inner square 2230. Inside the inner square 2230, a second (or inner) gauze pad 2270 is fitted. Thus, the outer gauze pad 2260 contacts the eight electrodes 2120 and the inner gauze pad 2270 contacts the center electrode 2110. The inner square 2230 provides electrical separation between the inner gauze pad 2270 and the outer gauze pad 2260, and the outer square 2240 provides the outer gauze pad 2270 in the correct position with respect to the top surface of the plate 2210. Provides the ability to hold. The inner gauze pad 2270 and the outer gauze pad 2260 preferably have a thickness of 5 mm, which is the same as the thickness of the inner square 2230 and the outer square 2240.

In a preferred embodiment of the thirteenth embodiment, the outer gauze pad 2240 is inhaled with about 2 ml of saline (1% NaCl) and the inner gauze pad is inhaled with 0.5 ml of 5% lidocaine hydrochloride aqueous solution. .. Plate 2210 is placed between the patient's skin and the vibrating head of the probe.

In experiments performed on mice, the same current x time (where "x" is a multiplication operator) was set to the product value by the system and method according to thirteenth embodiment after microskin ablation treatment. Comparison with the iontophoresis device proves that the same amount of radioactive lidocaine is passed into the skin, where the current of the iontophoresis device is positive in the first positive phase and the second negative phase. The current of the system and method according to the thirteenth embodiment is set so that the average current of the product per pulse for the total time of the positive pulse has the same value as the positive phase of the iontophoresis device. , And the average current of the product per pulse for the total time of the negative pulses was set to have the same value as the negative phase of the iontophoresis device.

The above experiments demonstrated the advantages of the present invention according to the thirteenth embodiment in comparison with the use of iontophoresis devices. One advantage of the present invention is that the use of symmetric pulsed currents, in part, contributes to the absence of chemical reactions at the electrodes. Iontophoresis devices, on the other hand, produce electrolysis with changes in PH on the skin, which can result in adverse effects on the skin (eg, redness of the skin, inflammation of the skin, burns of the skin). There is. The use of the present invention according to the thirteenth embodiment is to apply a skin absorption treatment to the skin after applying microskin ablation to the skin to remove the stratum corneum (the outer layer of the skin exposed to the outside air). Although it is possible to provide, providing skin treatment using an iontophoresis device can result in higher damage if PH changes occur on the skin. This problem does not occur when the thirteenth embodiment of the present invention is used in place of the iontophoresis device. By using both techniques together (microskin ablation and subsequent treatment by use of the system or method according to the thirteenth embodiment), higher dermatological substance flow (higher flow of skin therapeutic material, as demonstrated by experiments on mice). About 50% increase) is obtained.

An additional advantage of the present invention according to the thirteenth embodiment when compared to the iontophoresis device is that the present invention according to the thirteenth embodiment uses any type of ionized aqueous substance as a skin therapeutic substance. It does not involve the risk of altering the chemical properties of the applied substance, and thus the risk of chemical reactions at the electrodes that can have adverse effects on the skin. The induction of adverse effects on the skin is a situation that can occur in iontophoresis therapy, which inhibits the application of many substances to the skin. This problem does not occur when a system or method according to the thirteenth embodiment is used instead.

In the alternative embodiment of the thirteenth embodiment, the two gauze pads are replaced with two hydrogel pads, the outer pad contains 1% NaCl and the inner pad contains 5% lidocaine hydrochloride. In addition to NaCl, another type of solution for the outer pad may contain other aqueous ionized conductive material, or the same material used for the inner pad to obtain a larger absorption surface. it can. In addition to lidocaine hydrochloride, as a solution for another type of inner pad: ascorbic acid, jaluronic acid, collagen, elastin, cogic acid, salicilic acid, liposomes, anti-inflammatory steroids , Or local anesthetics can be included.

In this embodiment, the use of mechanical vibrations synchronized with the burst of pulses results in a small increase in absorption rate and further reduces the patient's perception of the pain produced by the current pulse, thereby being tolerated by the patient. It is possible to increase the possible pulse current (ie, the pulse current level that does not cause physical discomfort to the patient).

Although the thirteenth embodiment is described in connection with the electrode configuration as shown in the third embodiment described above, other types of electrode configurations may be used. If the first set of electrodes is covered by a first solution absorption pad as described above, the second set of electrodes that are not electrically connected to the first set of electrodes is on top. Covered by a second solution absorption pad as described.

Experimental application of some of the skin absorption device embodiments described above to the skin has demonstrated significant changes in the results and rates of substance absorption. Analysis was performed over areas of pre-exfoliated skin as well as adjacent areas without pre-exfoliation using standard microskin strips available on the market. From this analysis, the results obtained within the ablated area are extremely constant and reproducible, whereas the unexfoliated area is variable and somewhat inconsistent. It was proved that. This discord acts as a barrier to the absorption of substances applied to the skin by the stratum corneum of the skin (the outermost layer of the keratinized or dead epidermis), which in turn increases the electrical resistance of the skin. As a result, the absorption effect of the skin absorption treatment according to the present invention is somewhat reduced.

The thickness of the stratum corneum varies from individual to individual, and even within the same individual, it varies with time. This causes variability that makes it difficult to find a standard application time for skin absorbers according to various embodiments of the invention. For this reason, according to yet another embodiment of the present invention, the skin absorption therapeutic method comprises performing microskin ablation prior to application of the skin absorbent device, to an embodiment in which microskin ablation is not first performed. By comparison, it provides more consistent and reproducible results. Microskin ablation that should be performed prior to skin absorption treatment is referred to by Mattioli Engineering, Ltd., such as US Pat. No. 6,322,568 and US Pat. No. 6,039,745, which are incorporated by reference in their entirety. It can be as described in various transferred US patents, or any other type of conventionally known skin ablation treatment.

Preferably, to exfoliate the stratum corneum of the skin over a thickness of 100 microns in the area where treatment with the skin absorption increasing device according to one of the embodiments of the present invention will be subsequently applied. A 3-minute exfoliation treatment is performed. Ideally, skin absorption treatment is given immediately after the completion of skin ablation treatment (eg, within 5 minutes). Naturally, the length of time for other skin ablation treatments, the depth at which the stratum corneum is removed, and the time interval between skin ablation treatments and skin absorption treatments are also planned, but as mentioned above, in the end. It is attributed to the scope of the present invention.

Next, the fourteenth embodiment will be described in detail. A fourteenth embodiment of the present invention is directed to methods and devices for increasing skin absorption and reducing cellulite and can be used as a modification of the fifth or eighth embodiment described above. In a fourteenth embodiment, the skin is controlled by the inventor to warm the skin surface and the area underneath the skin surface having cellulite and adipose tissue in order to improve the speed and efficiency of cellulite reduction. It was determined that it would increase the absorption rate of the substance to be introduced into (thus, to the lower area of the skin with cellulite as well as adipose tissue). This results in a faster and more efficient reduction of cellulite and adipose tissue in the patient.

Warming the skin can be achieved in at least two different ways: (a) a 50 W infrared heating lamp placed between the rollers placed on the head of the probe, or (b) a frequency of 13.54 MHz, output. Using a radio frequency of 50W, RF is delivered to the skin via a roller located at the head of the probe.

By way of exemplifying, rather than limiting, warming the skin with control, the skin surface is preferably warmed to a temperature of about 50 ° C at a rate of 5 ° C per second. More generally, it can warm the skin to temperatures of 45 ° C-60 ° C at a rate of 2 ° C-40 ° C per second.

When warming over radio frequencies, the radio frequencies are preferably continuous waves (CW), but instead have waves with a specific duty cycle (eg between 20% and 80%). You can also. In the alternative configuration, a temperature sensor is provided on the head of the probe to determine when the skin reaches the desired temperature. When the desired skin temperature is reached, the heat supply to the skin is controlled so that the desired skin temperature is maintained (and thus does not rise). For example, when it is detected that the patient's skin reaches 50 ° C, the radio frequency is controlled, which is switched from the CW signal to the pulse signal to apply less heat to the skin, during skin treatment. Its desired skin temperature is maintained throughout.

In addition to the use of a 50W infrared heating lamp, an LED (light emitting diode) or laser diode may be used instead, and a visible light range (eg, 300 μm to 10 μm) may be used instead of the infrared range. You may. Moreover, the power output of the lamp does not necessarily have to be 50W (for example, it can be in the range of 25W-100W).

In addition to the use of 13.54MHz, 50W radio frequency signals, 0.5MHz to 27MHz radio frequencies may be used instead, and the power output may be any of 1 to 100W. it can. Low radio frequencies will warm the deeper areas below the skin surface, and high frequencies will warm the shallower areas below the skin surface. Therefore, the particular radio frequency used depends on the area of the patient to be treated.

Here, with reference to FIGS. 25, 26, and 27, one possible embodiment of the fourteenth embodiment is shown. An infrared light emitting diode (LED) 2510 is provided on the probe head, in which the LED 2510 is located on the surface of the vibrating plate 810 facing the skin. When the skin is sucked into the probe head via the vacuum chamber 820 as well as the vacuum pump 855, the skin 850 is warmed via the LED 2510, thereby warming (solubilizing) the cellulite / adipose tissue beneath the skin surface. Occurs). When a substance is applied to the skin via a probe, the substance can easily attach to warmed cellulite / adipocytes, which makes it easier for the patient to metabolize the cellulite / adipocytes. As a result, cellulite and fat are reduced. Figures 25, 26, and 27 also show the rubber belt 840 coupled around the roller 830.

Then, with reference to FIGS. 28, 29, 30, and 31, another possible embodiment of the fourteenth embodiment is shown. In FIGS. 28, 29, and 30, the roller is a conductor roller 830', which provides a means for a burst of electrical pulses that will be applied to the patient's skin. These conductor rollers 830'also provide a mechanism for radio frequency signals for heat supply applied directly to the patient's skin. The roller 830'is preferably a metal roller or a conductive plastic roller. In addition, FIG. 30 also shows coaxial cables 3010, which are the bursts of electrical pulses and radio frequency signals for heat supply that will be provided to rollers 830'placed on the head of the probe. Provide a supply channel for. FIG. 31 shows one possible way in which these signals can be delivered to the roller 830', in which the radio frequency generator 3110 outputs the radio frequency signal, which in turn passes the first filter 3120. As you can see, it is output on the coaxial line 3010. The electrical signal burst generator 3130 outputs a burst of electrical pulses, which then passes through a second filter 3140 and is output onto coaxial line 3010. The first filter 3120 has a bandwidth that prevents bursts of electrical pulses from entering the radio frequency generator 3110, and the second filter 3150 has a radio frequency signal for heat supply that is an electrical signal burst generator. It has a bandwidth that prevents it from entering the 3140. One possible circuit implementation of the electrical signal burst generator 3140 is shown, for example, in Figure 4.

As mentioned in connection with the embodiments described above, the preferred frequency of each electrical pulse within a burst of electrical pulses is between 2500 and 3000 Hz, so the first filter 3120 blocks this particular frequency range. It can be configured to (but pass frequencies above 1MHz). Similarly, the second filter 3150 blocks the frequency range above 1MHz, but can be configured to allow the passage of lower signals (eg, low-pass filters).

Next, a fifteenth embodiment of the present invention will be described with reference to FIGS. 32A to C, 33A, 33B, and 33A to C. This fifteenth embodiment provides an alternative method of supplying material to the patient's skin via a component coupled to the head of the probe that provides electrical pulses and / or mechanical vibrations to the patient's skin. In this regard, the fifteenth embodiment is similar to the thirteenth embodiment described above, but the method of applying the skin therapeutic substance to the skin is different.

FIG. 32A shows a cross-sectional view of the head 3210 of the probe coupled to the head attachment 3220. The head attachment 3220 is preferably made of polypropylene (which can be a brass component) and has nine cylindrical openings 3222 into which nine independent cylindrical sponges can be fitted. .. FIG. 32B shows a front view of the head attachment 3220, FIG. 32C shows one cross-sectional view of the cylindrical opening 3222 of the head attachment 3220 with the cylindrical sponge 3224 fitted into the cylindrical opening 3222. It is shown as a state. Instead of using a cylindrical sponge, a cotton gauze or hydrogel pad can be fitted into the cylindrical opening 3222, or a combination of these components can be used (eg, 3 gauze pads, 3). Use a sponge and 3 hydrogel pads). The attachment head 3220 is shown as having nine cylindrical openings 3220 for the case where nine electrodes are placed in front of the probe, and the side view of FIG. 32A shows of those electrodes 3230. Three are shown (the remaining electrodes on the front of the probe are not shown blocked, but see Figure 2C for the placement of the nine electrodes).

Each of the nine electrodes on the front of the probe is located at one end of the cylindrical opening 3222, where the sponge 3224 is the other end of the cylindrical opening 3222, as best shown in FIG. 32B. It protrudes slightly from. The sponge is thus configured to contact the area on the skin of the patient to be treated via this probe. Each sponge 3222 can be immersed in a substance that will be applied to the patient's skin, for example, a hydrogel pad can be inhaled with 4% lidocaine. An electrical pulse was applied to the patient's skin via an electrical pulse (these are indirectly connected to the patient's skin via the sponge 3222) and / or supplied to the sponge 3222 by mechanical vibration. The substance is easily absorbed into the patient's skin.

In a preferred configuration, the attachment head 3220 is a disposable component that can be discarded after treatment of the patient. The attachment head 3220 can be detachably coupled to the probe head 3210 using a variety of methods, such as snap fit coupling or another method described in connection with other embodiments. Not surprisingly, if the placement and number of electrodes on the probe head 3210 are different, the placement and number of openings on the attachment 3220 will be modified to accommodate that particular placement.

Figures 33A and 33B show a second type of electrode arrangement, in which the center electrode 3310 is located below the centered sponge 3320 and the peripheral electrode 3330 is located around the sponge 3340. It is provided on the underside. In this configuration, the probe head 3305 is circular and the attachment head 3350 accommodates an inner cylindrical opening 3360 for accommodating a centrally located sponge 3320 and a surrounding sponge 3340. It has an outer cylindrical opening 3370. FIG. 33A shows a cross-sectional view of the probe head 3305 with the attachment head 3350 attached, and FIG. 33B shows the attachment with a sponge fitted into each opening of the attachment head 3350. -The front view of the head 3350 is shown.

Figures 34A-34C show a third type of electrode arrangement on the probe head 3405. This arrangement corresponds to, for example, those shown in FIGS. 17 and 18, in which there is no centered electrode on the probe head 3405. In this configuration, three electrodes 3410 are provided under each of the three cylindrical openings 3420 of the attachment head 3430, which can be made of, for example, polypropylene. Each of the cylindrical openings 3420 can be filled with a sponge or gauze that has inhaled a substance applied to the patient's skin. FIG. 34A shows a cross-sectional view of the probe head 3405 with the attachment head 3430 detachably attached, and FIG. 34B is a front view of the attachment head 3430 (no sponge in opening 3420). State), FIG. 34C shows one cross-sectional view of the cylindrical opening 3420 with the sponge 3450 fitted inside.

The various embodiments of the present invention have been described above in accordance with the present invention. Many modifications and modifications can be made to the techniques and structures described and illustrated herein without departing from the scope of the invention. Therefore, it should be understood that the devices described herein are merely exemplary and do not limit the scope of the invention. For example, frequency of the mechanical vibration frequency of the bursts and the number electrical pulses, as described in connection with several different embodiments, if also be the same, and they are an integral multiple or submultiple of each other You can also do it. Thus, for example, the burst frequency of an electrical pulse of 50 Hz may be used with mechanical vibration of 100 Hz, which also increases the absorption of the patient's skin and reduces sensitivity (eg, reduces pain). The effect is achieved. Alternatively, the burst frequency of an electrical pulse of 200 Hz may be used with mechanical vibration of 100 Hz, which also achieves the effect of increasing absorption and reducing sensitivity. In addition, the plate of the probe on which the electrodes are located can be a sterilized disposable part (eg, a part that is removed from the sterilized container and then attached to the probe head). In this embodiment, after completing the treatment of the patient, the disposable plate is removed from the probe and discarded, and then a new sterile plate (with electrodes on top) is used to treat another patient. Attach to the probe. This type of embodiment significantly reduces contamination between different patients because the portion of the probe that comes into direct contact with each patient is discarded after each patient's treatment.

<figref num="1A">It is a side view of the vibration mechanism arranged in the apparatus according to this invention.</figref><figref num="1B">It is a front view of the vibration mechanism of FIG. 1A.</figref><figref num="2A">FIG. 5 is a plan view showing an array of electrodes provided on the outer surface of a vibrating plate facing the skin according to a first embodiment of the present invention.</figref><figref num="2B">FIG. 5 is a plan view showing an array of electrodes provided on the outer surface of a vibrating plate facing the skin according to a second embodiment of the present invention.</figref><figref num="2C">FIG. 5 is a plan view showing an array of electrodes provided on the outer surface of a vibrating plate facing the skin according to a third embodiment of the present invention.</figref><figref num="3">FIG. 5 is a side view of a probe head used to provide both electrical and mechanical stimuli to the skin for better absorption of substances pre-applied to the skin in accordance with the present invention.</figref><figref num="4">An electrical circuit of a pulse generator that supplies electrical pulses to an array of electrodes placed on a vibrating plate provided at the end of the probe head according to one of the possible configurations of the device according to the present invention. It is a figure.</figref><figref num="4A">It is a waveform diagram which showed the square pulse train input to the pulse generator of FIG.</figref><figref num="4B">It is a waveform diagram which showed the exponential pulse train output from the pulse generator of FIG.</figref><figref num="5">FIG. 5 is a side view showing one configuration of a hand-held probe used to provide both electrical and mechanical stimuli to the skin according to one or more embodiments of the present invention.</figref><figref num="6">It is an electric circuit diagram which showed the connection of the current generator according to the 4th Embodiment of this invention.</figref><figref num="7">It is a side view which showed the element provided in the head part of the probe according to the 5th Embodiment of this invention.</figref><figref num="8">It is a front view of the head part of the probe according to the 5th Embodiment of this invention.</figref><figref num="9">It is a front view of the head part of the probe according to the 8th embodiment of this invention.</figref><figref num="10">It is a 1st cross-sectional view which showed the place where suction is not applied to the skin of the head part of the probe according to 8th Embodiment of this invention.</figref><figref num="11">It is the 2nd sectional view which showed the place where the suction is applied to the skin of the head part of the probe according to 8th Embodiment of this invention.</figref><figref num="12">It is explanatory drawing which showed the structure of the electroporation device according to the 9th Embodiment of this invention.</figref><figref num="13">FIG. 6 is an exploded perspective view showing components used to connect electrodes and wires to the head of an electroporation device according to a ninth embodiment of the present invention.</figref><figref num="14">It is a side view of the head of the probe used in the apparatus according to the 9th Embodiment of this invention.</figref><figref num="15">It is explanatory drawing which showed the back surface of the head of the probe in the apparatus according to the tenth embodiment of this invention together with a transformer.</figref><figref num="16">It is a front view of the head of the probe used in the apparatus according to the tenth embodiment of this invention.</figref><figref num="17">FIG. 5 is a front view of the head of a probe having three electrodes used in an apparatus according to the eleventh embodiment of the present invention.</figref><figref num="18">It is explanatory drawing which showed the back surface of the head of the probe which has three electrodes used in the apparatus according to eleventh embodiment of this invention, together with the transformer which provides the electric pulse to three electrodes.</figref><figref num="19">FIG. 5 is a waveform diagram showing a square wave input pulse and an exponential pulse with deviations for three transformers used in the apparatus according to the eleventh embodiment of the present invention.</figref><figref num="20">It is explanatory drawing which showed the gauze pad provided between the probe according to the twelfth embodiment of the present invention (the probe according to any one of the embodiments of the present invention) and the skin of a patient.</figref><figref num="21">It is explanatory drawing which showed the skin treatment device according to the thirteenth embodiment of this invention from various directions.</figref><figref num="22">It is explanatory drawing which showed the skin treatment device according to the thirteenth embodiment of this invention from various directions.</figref><figref num="23">It is explanatory drawing which showed the skin treatment device according to the thirteenth embodiment of this invention from various directions.</figref><figref num="24">It is explanatory drawing which showed the skin treatment device according to the thirteenth embodiment of this invention from various directions.</figref><figref num="25">It is explanatory drawing which showed one possibility of materialization of the skin treatment device according to 14th Embodiment of this invention.</figref><figref num="26">It is explanatory drawing which showed one possibility of materialization of the skin treatment device according to 14th Embodiment of this invention.</figref><figref num="27">It is explanatory drawing which showed one possibility of materialization of the skin treatment device according to 14th Embodiment of this invention.</figref><figref num="28">It is explanatory drawing which showed another possibility of materialization of the skin treatment device according to 14th Embodiment of this invention.</figref><figref num="29">It is explanatory drawing which showed another possibility of materialization of the skin treatment device according to 14th Embodiment of this invention.</figref><figref num="30">It is explanatory drawing which showed another possibility of materialization of the skin treatment device according to 14th Embodiment of this invention.</figref><figref num="31">It is explanatory drawing which showed another possibility of materialization of the skin treatment device according to 14th Embodiment of this invention.</figref><figref num="32A">It is explanatory drawing which showed one possibility of materialization of the skin treatment device according to the fifteenth embodiment of this invention.</figref><figref num="32B">It is explanatory drawing which showed one possibility of materialization of the skin treatment device according to the fifteenth embodiment of this invention.</figref><figref num="32C">It is explanatory drawing which showed one possibility of materialization of the skin treatment device according to the fifteenth embodiment of this invention.</figref><figref num="33A">It is explanatory drawing which showed another possibility of materialization of the skin treatment device according to the fifteenth embodiment of this invention.</figref><figref num="33B">It is explanatory drawing which showed another possibility of materialization of the skin treatment device according to the fifteenth embodiment of this invention.</figref><figref num="34A">It is explanatory drawing which showed still another possibility of materialization of the skin treatment device according to the fifteenth embodiment of this invention.</figref><figref num="34B">It is explanatory drawing which showed still another possibility of materialization of the skin treatment device according to the fifteenth embodiment of this invention.</figref><figref num="34C">It is explanatory drawing which showed still another possibility of materialization of the skin treatment device according to the fifteenth embodiment of this invention.</figref>

Code description

1 Motor 2 Screw 3 Slide 4 Frame 5 Piston 6 Syringe 7 Pipe (or Tube) 8 Center Electrode; Electrode 9 Peripheral Electrode 10 Head 11 Groove or Trough 12 Groove 110 DC Electric Motor 120 Eccentric Ring 130 Vibration Plate 210 Electrode Array 220 Electrode; Parallel metal strip 230 Circular electrode 233 Electrode 235 First electrical connection 237 Electrode 239 Second electrical connection 250 Electrical line 260 Electrical line 270 Electrical line 280 Electrical line 310 Vibration head 320 Electrode array 330 Skin 340 Material 400 Pulse generator 410 Transformer 420 Primary winding 430 Transistor; Switching transistor 440 Secondary winding 450 Electrical resistance 500 Hand-held probe; Probe 510 Outlet 610 DC current generator 705 Electrode array 710 Chamber; Dispenser or Chamber 720 Cream or Gel; Material 740 Roller; Conductor Roller 760 Liquid Spout 800 Head; Probe Head 810 Vibration Plate 820 Vacuum Chamber; Electrical Connection 830 Roller; Exposed Surface 830'Conductor Roller 840 Belt; Rubber Belt; Gap 845 Pipe 850 Skin 855 Vacuum Pump 1310 Motor 1320 Eccentric Ring 1330 Washer 1340 Screw 1350 Wire 1355 Wire 1365 Resistance 1375 Housing 1380 Screw 1500 Electrode 1510 Head 1530 Groove; Groove or Trough 1550 Tube 1560A Pulse Transformer 1560B Pulse Transformer 1560C Pulse Transformer 1560D Pulse Transformer 1560E Pulse Transformer 1560F Pulse Transformer 1560G Pulse Transformer 1560H Pulse Transformer 1560I Pulse Transformer 1700 Electrode 1710 Tube 1720 Groove 1810A Transformer 1810B Transformer 1810C Transformer 2010 Probe 2020 Vibration Head 2030 Electrode Array 2033 Gauze; Pad 2035 Skin Absorbent 2040 Patient Skin 2110 Center Electrode 2120 Peripheral Electrode 2130 Probe Head 2210 Plastic Layer; Plate 2230 Concentric Squares; Inner Squares 2240 Outer Gauze Pads; Outer Squares; Concentric Squares 2260 Outer Gauze Pads; First (or Outer) Gauze Pads 2270 Second (or Inner) Gauze Pads; Inner Gauze Pads Pad 2510 Infrared Light Emitting Diode (LED) 3010 Coaxial Cable; Coaxial Line 3110 Radio Frequency Generator 3120 First Filter 3130 Electrical Signal Burst Generator 3140 Second Filter 3150 Second Filter 3210 Probe Head 3220 Attachment Head; Head Attachment 3222 Sponge; Cylindrical Opening 3224 Cylindrical Sponge 3230 Electrode 3305 Probe Head 3310 Center Electrode 3320 Centered Sponge 3330 Peripheral Electrode 3340 Peripheral Sponge 3350 Attachment Head 3360 Inner Cylindrical Opening 3370 Outer Cylindrical Opening 3405 Probe Head 3410 Electrode 3420 Cylindrical Opening 3430 Attachment Head 3450 Sponge