JP2004065812A - Method and apparatus for transdermal introduction of medicine using ultrasonic vibration - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To efficiently perform the penetration of the skin and absorbing into blood of a medicine by the working of a voltage or an electric current together with working of ultrasound. <P>SOLUTION: A metal vibrator 11 ultrasonically vibrating is applied to the surface of the skin HF and is arranged so that the medicine YZ may exist between the vibrator 11 and the skin HF, the vibrator 11 is used as one electrode, the medicine YZ is ionized by impressing the voltage between one electrode and the other electrode DK in contact with sections other than the section to which the vibrator 11 is applied, and hence the ionized medicine YZ is permeated into the skin HF in a condition of giving to the skin HF ultrasonic vibration by the vibrator 11. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method and an apparatus for transdermally introducing a drug using ultrasonic vibration.
[0002]
[Prior art]
Conventionally, oral administration, injection into muscle or vein, and the like have been used as general methods of drug administration. Injection can cause pain and tissue damage, and oral administration has a difference in efficacy depending on factors such as diet. In addition, since only a part of the drug that has entered the blood reaches the affected area by these methods, it is necessary to administer a larger amount of the drug than necessary, which is a factor that causes an adverse effect due to the excessive amount.
[0003]
Therefore, a method of administering a drug from the skin, that is, a transdermal introduction method (a transdermal absorption method) has been proposed in order to deliver a necessary amount of the drug to a necessary place.
In the conventional transdermal introduction method, ultrasound is applied to a drug placed on the surface of the skin, and the drug is moved by the ultrasonic vibration to penetrate the skin.
[0004]
[Problems to be solved by the invention]
However, in the conventional transdermal introduction method, the drug permeates the skin due to the movement of the drug by the action of ultrasonic waves, but the permeation efficiency and absorption into the blood are not always sufficient. Further, the secondary effect of activating the skin cannot be expected much.
[0005]
The present invention has been made in view of the above-mentioned problems, and has as its object to ionize a drug together with the action of ultrasonic waves so that skin permeation and absorption into blood are efficiently performed.
[0006]
[Means for Solving the Problems]
In the method according to the present invention, a metal vibrator vibrating by an ultrasonic wave is applied to the surface of the skin, and the medicine is disposed between the vibrator and the skin, and the vibrator is moved to one side. And the drug is ionized by applying a voltage between the other electrode in contact with a portion other than the portion to which the vibrating body is applied, thereby applying ultrasonic vibration to the skin by the vibrating body. The ionized drug penetrates the inside of the skin in the closed state. As described above, the method is based on the vibrating electrode method in which the electromagnetic action of ultrasonic vibration is superimposed.
[0007]
Preferably, a first step of maintaining a state in which the ultrasonic vibration by the diaphragm and the voltage are applied to the skin for a predetermined time, a second step of turning off the ultrasonic vibration and the voltage by the diaphragm, And the first step and the second step are executed alternately. In this manner, the introduction treatment can be performed by selectively switching the compatible polarity on the introduction side.
[0008]
In addition, a metal first vibrator that vibrates by ultrasonic waves is applied to the surface of the skin, and the first vibrator and the skin are arranged so that a drug is present between the first vibrator and the skin. The vibrating body is used as one electrode, and the drug is ionized by applying a voltage between the vibrating body and the other electrode that is in contact with a part other than the part to which the first vibrating body is applied. In a state where ultrasonic vibration by the vibrator is applied to the skin, the ionized drug penetrates into the skin, and the second vibrator made of metal that vibrates with the ultrasonic wave is applied to the skin to which the first vibrator is applied. The first vibrating body is applied to a portion of the surface of the skin different from the surface and arranged so that a drug is present between the second vibrating body and the skin; By applying a voltage between them as the other electrode The serial drug ionize, thereby infiltrating ionized drug in the state where an ultrasonic vibration by the second vibrator gave the skin within the skin.
[0009]
In addition, a first vibrator made of metal vibrating by ultrasonic waves is applied to the surface of the skin, and the first vibrator is arranged so that a drug is present between the first vibrator and the skin. A second electrode made of a metal that applies a first voltage between the electrode and the other electrode in contact with a part other than the part to which the first vibrating body is applied, and vibrates by ultrasonic waves; Applying a vibrating body to a portion of the skin surface different from the skin surface to which the first vibrating body is applied, and disposing a drug between the second vibrating body and the skin; A second voltage is applied between the first vibrator and the second vibrator.
[0010]
Preferably, the first voltage is a voltage at which the first vibrator is negative and the electrode is positive, and the second voltage is a voltage at which the second vibrator is negative and the second voltage is negative. One vibrator has a positive voltage.
[0011]
Further, the first vibrator has a plate shape and is provided with a hole, and the second vibrator is arranged in the hole.
An apparatus according to the present invention includes a first vibrator made of metal that vibrates with an ultrasonic wave for application to the surface of the skin, and an ultrasonic wave for applying to a surface of the skin different from the first vibrator. Voltages are respectively applied between the vibrating metal second vibrator, the electrode member, the first vibrator and the electrode member, and between the second vibrator and the first vibrator. And a voltage generating circuit for applying the voltage.
[0012]
Preferably, the first vibrator has a plate shape and is provided with a hole, and the second vibrator has a shape that can be arranged in the hole.
In addition, in the arrangement of the active system of the drug in the percutaneous introduction device, the conventional type is operated directly through an aqueous solution permeation (cancer) layer by direct application with an aqueous solution drug or by the higase method, and the quantitative Although there was a drawback that waste and the chemical reaction of the aqueous solution were fast, the apparatus of the present invention dipped in water immediately before the need, using a dry, drug, or paper-pate-like drug discovery method, and made it into a Japanese paper form. Paper tape is a drug discovery that acts as a drug aqueous solution impregnated layer as it is, and Washi tape propagates ultrasonic vibrations well to the front and back surfaces, and also contains an aqueous solution as an electrically conductive layer, resulting in conductivity. As a layer that protects the skin even in the form of an aqueous solution layer, it is possible to use a paper tape drug discovery that can form an indirect contact method that is not directly in contact with the skin opposite to the vibrating body and the electrode body. is there. (Dry-drug type paper tape agent in which a drug is held between layers in advance) It is used as a drug material that is advantageous in terms of storage stability and cost.
[0013]
In other words, a drug holding material applied between the vibrating body vibrating by ultrasonic waves and the surface of the skin, characterized in that the drug is held in a layer of Japanese paper tape and dried. I do.
[0014]
BEST MODE FOR CARRYING OUT THE INVENTION
[First Embodiment]
FIG. 1 is a view for explaining a method for transdermally introducing a drug according to the first embodiment of the present invention, FIG. 2 is an enlarged view showing a state when an ultrasonic head TH is applied to the surface of the skin, FIG. 3 is a diagram illustrating the timing of applying ultrasonic vibration and voltage.
[0015]
As shown in FIGS. 1 and 2, the apparatus 1 for transdermally introducing a drug includes an ultrasonic head TH, a grip electrode DK, a drive circuit 30, and a voltage generation circuit 40. The ultrasonic head TH holds the diaphragm 11 against an appropriate part of the body, for example, the surface of the skin HF of the arm HD, and presses the diaphragm so that the drug YZ exists between the diaphragm 11 and the skin HF. 11 or skin HF.
[0016]
As the drug YZ, for example, a solution of various nutrients such as vitamin A, vitamin C or vitamin E, collagen or carbohydrate, a solution of a physiologically active substance such as antibiotics, hormones, neurotransmitters, magnesium or sodium For example, solutions of various substances, other pharmacological raw materials having pharmacological action, anesthetics, insulin, and other various chemicals can be used. These exist as an ionized solution or aqueous solution by being applied in the present embodiment.
[0017]
The gripping electrode DK is a cylindrical rod or cylinder made of a metal such as iron, copper, or titanium, or carbon, and the surface thereof is in electrical contact with the skin HF, for example, by gripping with a hand. Instead of such a gripping electrode DK, a metal plate may be attached to the surface of skin HF, a metal needle may be driven from the surface of skin HF, or the electrode may be embedded in the subcutaneous tissue.
[0018]
An ultrasonic signal (ultrasonic driving power) is applied to the ultrasonic head TH, and the diaphragm 11 is ultrasonically vibrated. At the same time, a voltage is applied between the diaphragm 11 and the grip electrode DK. The voltage includes a positive DC voltage, a negative DC voltage, a voltage including an AC component, and the like. Details will be described later.
[0019]
For example, the ultrasonic signal and the voltage are applied continuously for about 1 to 10 minutes for applying the ultrasonic signal. Further, the application and the pause may be repeated plural times at appropriate intervals. In other words, as shown in FIG. 3, the first step of maintaining the state in which the ultrasonic vibration and the voltage by the vibration plate 11 are applied to the skin for a certain time T1, and turning off the ultrasonic vibration and the voltage by the vibration plate 11 And the second step of maintaining the state described above for the time T2 is alternately repeated. In this case, the period is Ts. For example, a pause of 0.1 to 2 minutes is performed every 0.1 to 2 minutes and this is repeated a plurality of times. A pause of 2 minutes is performed every 5 minutes and repeated a plurality of times.
[0020]
The drug YZ applied on the surface of the skin HF is ionized. It may be a negative ion (anion) or a positive ion (cation). These ions permeate into the skin with the help of the voltage (or current) applied between the diaphragm 11 and the grip electrode DK. This phenomenon itself is known as iontophoresis (ion introduction method). Then, the ionized drug YZ moves more effectively by the ultrasonic vibration, penetrates the skin and enters the subcutaneous tissue. It is considered that this is because the penetration force of the skin HF is increased several times to several tens times by the ultrasonic vibration.
[0021]
That is, the drug YZ effectively penetrates the skin by the electric current flowing on the surface of the skin HF, and the active ingredient is efficiently absorbed into the blood. It is considered that the current flowing through the skin HF causes the ionization or esterification of the drug YZ to proceed, thereby improving the uniformity of the surface of the skin HF to which the drug YZ is applied, and improving the diffusion and dispersibility of the drug YZ. . Further, the skin HF is ultrasonically vibrated and the stimulation current flows through the skin HF, thereby activating the skin.
[0022]
The details will be described below.
FIG. 4 is a front sectional view of the ultrasonic head TH, and FIG. 5 is an exploded perspective view of the ultrasonic head TH.
[0023]
4 and 5, the ultrasonic head TH includes a vibration plate 11, an insulating plate 12, an ultrasonic vibrator 13, a cover plate 14, a buffer support member 15, a mounting plate 16, a screw 17, and the like.
[0024]
The diaphragm 11 includes a disc-shaped bottom portion 11a, a cylindrical portion 11b surrounding the bottom portion 11a, and a flange portion 11c provided on an outer peripheral edge of an upper end of the cylindrical portion 11b which is an opening of the diaphragm 11. Has a substantially cylindrical shape with a bottom. The boundary between the bottom 11a and the cylindrical portion 11b is formed in a smooth radius. The diameter of the bottom 11a is, for example, 20 to 50 mm.
[0025]
As a material of the diaphragm 11, a metal material such as carbon steel, a stainless alloy, an aluminum alloy, a nickel alloy, and various other alloys is used.
Specifically, for example, Hastelloy superalloy C-22 manufactured by Mitsubishi Materials Corporation is suitably used. This alloy does not contain chromium Cr and has excellent corrosion resistance. A thickness of a fraction of a millimeter to 1 millimeter, for example, 0.5 millimeter or 0.6 millimeter is used.
[0026]
The vibration plate 11 is vibrated by ultrasonic waves by the ultrasonic vibrator 13. When the ultrasonic transducers 13 are sequentially driven in the circumferential direction, the center of vibration of the diaphragm 11 moves in the circumferential direction. As described above, the vibration plate 11 functions as a rotating wave vibration body. Diaphragm 11 is used as one electrode for flowing a current to skin HF.
[0027]
The insulating plate 12 has a disk shape having an outer diameter slightly smaller than the bottom 11 a of the diaphragm 11. As a material of the insulating plate 12, an elastic material having good insulating properties is used. For example, a synthetic resin such as a hard epoxy resin, in particular, a synthetic resin called a polymer metal can be used. Specifically, for example, “Kepler” manufactured by GE can be used.
[0028]
The insulating plate 12 is provided on its front and back surfaces with a conductive layer made of copper foil having a thickness of about 30 microns and having good conductivity. The conductive layers on the front and back surfaces are electrically independent of each other. Such a conductive layer is formed by lamination, plating, coating, sticking, or any other appropriate method.
[0029]
The insulating plate 12 is adhered to the back surface of the diaphragm 11 with a structural adhesive or the like. The insulating plate 12 electrically insulates the ultrasonic vibrator 13 from the vibration plate 11 and acoustically couples the ultrasonic vibrator 13 and the vibration plate 11 almost completely elastically. That is, the insulating plate 12 functions as an electrical insulating layer for the ultrasonic vibrator 13 and also functions as an elastic matching layer for ultrasonic vibration.
[0030]
A plurality of ultrasonic transducers 13 are provided. In the present embodiment, it is composed of eight ultrasonic transducers 13a to 13h. Each of these ultrasonic transducers 13a to 13h is made of, for example, a PZT-based disc-shaped piezoelectric ceramic plate.
[0031]
Of the eight ultrasonic transducers 13a to 13h, seven ultrasonic transducers 13b to 13h are arranged circumferentially on the back surface (inner surface side) of the bottom 11a of the diaphragm 11, and the remaining one is provided. The ultrasonic transducers 13a are arranged at the center of the circle. These ultrasonic transducers 13 are arranged on the surface of the insulating plate 12 such that their polarization directions are the same, and are bonded by a structural adhesive or the like.
[0032]
One electrode of each ultrasonic transducer 13 is commonly connected to the conductive layer on the surface of the insulating plate 12 directly or via a wire, and the other respective electrodes are individually drawn out via a cable. ing. Therefore, the cable has a total of nine wires, including eight wires individually connected to each electrode of each ultrasonic transducer 13 and one wire commonly connected to the conductive layer on the surface of the insulating plate 12. Consists of electric wires. Note that the number of electric wires of the cable varies depending on the number of ultrasonic transducers 13, the connection method, the driving method, and the like.
[0033]
The cover plate 14 is an annular plate made of stainless steel or the like. The outer diameter of the flange 11c of the diaphragm 11 is the same as that of the flange 11c. A hole 14a for inserting a cable is provided at the center, and screw holes 14b, 14c, and 14d for mounting are provided around the hole 14a.
[0034]
The cover plate 14 is placed over the opening of the diaphragm 11, and is elastically sandwiched and supported integrally with the flange 11 c by the buffer support member 15. By screwing the screw 17 into the screw holes 14b, 14c, 14d, the ultrasonic head TH is mounted on an appropriate mounting plate 16.
[0035]
The buffer support member 15 is formed in an annular shape so as to fit into the opening of the diaphragm 11 and the outer periphery of the edge of the cover plate 14, and supports them elastically. The buffer support member 15 can be manufactured by molding using a synthetic rubber material such as a nitrile rubber type or a silicon rubber type.
[0036]
The mounting plate 16 is made of a synthetic resin or a metal material. The mounting plate 16 may be provided as a part of a gripping member for operation by a doctor or a nurse. The ultrasonic head TH is mounted on the mounting plate 16 by screws 17.
[0037]
FIG. 6 is a diagram illustrating an example of the drive circuit 30, and FIG. 7 is a diagram illustrating an example of the voltage generation circuit 40.
In the drive circuit 30 shown in FIG. 6, the upper circuit in the circuit diagram forms a rectangular wave transmission circuit T using an inverter. By varying the resistance V1, the period of the rectangular wave S1 changes. The circuit below the circuit diagram constitutes an ultrasonic transmission circuit F using an inverter. The frequency of the ultrasonic signal S2 changes by changing the resistance V2 and by switching the switch S to select the capacitance of the capacitor. The frequency is set according to the ultrasonic transducer 13 used.
[0038]
In the gate circuit G, the ultrasonic signal S3 intermittently transmitted is obtained by the logical product of the rectangular wave S1 and the ultrasonic signal S2. This is power-amplified by the transistor U and output as an ultrasonic signal SU. The ultrasonic signal SU is sequentially applied to the ultrasonic transducers 13a to 13h so that they are sequentially driven in the circumferential direction.
[0039]
The rotation direction of the vibration of the diaphragm 11 can be reversed by reversing the order of the ultrasonic signals SU applied to the ultrasonic transducers 13a to 13h. Further, the duty ratio of the rectangular wave S1 may be variably adjusted. Instead of sequentially driving these ultrasonic transducers 13a to 13h, they may be driven simultaneously and simultaneously. As described above, the number, arrangement, connection method, and the like of the ultrasonic transducers 13 can be determined as appropriate. For example, only one ultrasonic vibrator 13 may be provided, and the vibration plate 11 may be ultrasonically vibrated by the single ultrasonic vibrator 13. Alternatively, about two or three ultrasonic transducers 13 may be provided and driven at the same time to cause ultrasonic vibration. In this case, a plurality of ultrasonic transducers 13 may be arranged so as to be arranged on a straight line.
[0040]
The time width T1, period T2, and (T1 + T3) of the ultrasonic signal SU can be selected according to the compliance of the ultrasonic transducer 13 and the diaphragm 11, the thickness of the skin, and the like. Further, it may be selected so as not to generate a standing wave on the vibration surface of the diaphragm 11.
[0041]
In the voltage generation circuit 40 shown in FIG. 7, a DC power supply is used, and the charging / discharging action of the inductance L and the capacity C is switched by the transistor TR-1. The oscillation frequency of the OSC is controlled by a control signal from the microcomputer control circuit 411. A waveform can be selected by a waveform selection button. Intermittent driving of on / off is performed by a bridge connection circuit of transistors, and a voltage is alternately generated between the electrodes A and B. The electrode A and the electrode B are connected between the diaphragm 11 of the ultrasonic head TH and the grip electrode DK.
[0042]
At this time, for example, a voltage of about 0.8 to 3 volts is applied. The frequency of the AC component is, for example, about 10 to 200 Hz. The commercial power supply may be full-wave or half-wave rectified to leave a pulsating flow to generate a voltage including an AC component. In that case, the frequency of the AC component is 50, 60, 100, or 120 Hz. A pulse having a frequency of about 1 to 200 Hz may be applied. Alternatively, a stimulation pulse having a frequency about three times the frequency of the heartbeat may be applied. Instead of the pulse, a rectangular wave or a square wave may be applied.
[0043]
Various waveforms such as those shown in FIGS. 8 and 9 are used as voltage waveforms.
In FIG. 8, a voltage obtained by superimposing an AC component voltage ACV close to a sine wave and a DC voltage DCV having a voltage larger than half the amplitude of the AC component voltage ACV is applied.
[0044]
FIG. 9 shows, in order from the top, a square wave, a half-wave rectified wave, an exponentially increasing wave, a contrast-type increasing wave, and a spike wave. The voltage of these waveforms is used as an AC component voltage, and a voltage obtained by superimposing a DC voltage on the AC component voltage is applied. Note that, for example, the peak value and the duty ratio of the square wave can be variously appropriate.
[0045]
With the configuration described above, ultrasonic vibration is output from the bottom 11a of the diaphragm 11 in a direction perpendicular to the surface thereof, and is output so as to scan along the circumference of the bottom 11a and rotate. Thereby, the ultrasonic vibration is transmitted to the drug YZ, and the ultrasonic vibration penetrates vertically and deeply into the skin HF, and the drug YZ penetrates the skin HF. By the electric current including the AC component flowing on the surface of the skin HF, the drug YZ effectively penetrates the skin and enters the subcutaneous tissue. A cosmetic effect can also be obtained by the ultrasonic vibration and the stimulation current.
[0046]
According to the above-described embodiment, the drug YZ is transcutaneously introduced by ultrasonic vibration, and the ion implantation is performed by electric current by the combined use of the ultrasonic vibration electrode method, so that the drug YZ effectively penetrates the skin. And is efficiently absorbed into the blood.
[Second embodiment]
FIG. 10 is a view for explaining a method for transdermally introducing a drug according to the second embodiment of the present invention, and FIG. 11 is an enlarged view of a state where two ultrasonic heads THB and THC are applied to the surface of the skin. FIG.
[0047]
As shown in FIGS. 10 and 11, an apparatus 1B for transdermally introducing a drug includes ultrasonic heads THB and THC, grip electrodes DK, drive circuits 30B and 30C, and a voltage generation circuit 40B.
[0048]
The ultrasonic head THB includes ultrasonic vibrators 13Ba and 13Bb made of piezoelectric ceramics and the like, and a vibrating plate 11B made of metal such as stainless steel. Diaphragm 11B has a spatula-like shape, and its leading edge has a smooth curve. A hole 21 is provided at the center of the tip of the diaphragm 11B. As such an ultrasonic head THB, it is possible to use a vibration mechanism described in International Publication WO98 / 48764.
[0049]
The ultrasonic head THC includes an ultrasonic vibrator 13C made of a piezoelectric ceramic or the like, and a vibrator 11C made of a metal such as stainless steel. The vibrating body 11C is of various shapes, such as a simple rod-like shape with a smooth tip at the tip, and a shape having a sandwiching portion so that absorbent cotton or the like can be sandwiched at the tip. Can be used.
[0050]
The drive circuits 30B and 30B supply ultrasonic vibration signals to the ultrasonic heads THB and THC, respectively. Thus, the vibration plate 11B and the vibration body 11C are ultrasonically vibrated independently of each other. The configuration and the like of the drive circuits 30B, 30B are basically the same as those of the drive circuit 30 described above.
[0051]
The voltage generation circuit 40B generates and supplies voltages that give potentials independent of each other to the ultrasonic head THB, the ultrasonic head THC, and the gripping electrode DK. That is, the voltage generation circuit 40B includes three terminals A, B, and C for supplying voltages to the diaphragm 11B of the ultrasonic head THB, the vibrator 11C of the ultrasonic head THC, and the gripping electrode DK, respectively. Various voltages are output from the terminals A, B, and C by switching modes.
[0052]
FIG. 12 is a circuit diagram showing an example of the voltage generation circuit 40B, and FIG. 13 is a diagram showing a mechanism of the bipolar induction method by the voltage generation circuit 40B.
In FIG. 12, a current from a constant current source is controlled by a switching element and distributed to terminals A to C.
[0053]
In FIG. 13, three terminals A, B, and C are provided, and a current for ionizing a drug YZ in ion introduction is supplied as an ion dissociation power supply.
As an example of the output voltage of the terminals A, B, and C, the terminal A is 0 volt, the terminal B is -1 volt, and the terminal C is -2 volt. Further, the terminal B may be set to minus several volts, and the terminal C may be set to minus several volts to tens of volts lower than that. That is, in this case, the diaphragm 11B is negative with respect to the gripping electrode DK, and the vibrating body 11C is negative with respect to the diaphragm 11B. The voltage between the terminals AB corresponds to the first voltage of the present invention, and the voltage between the terminals BC corresponds to the second voltage of the present invention.
[0054]
A constant current source may be used as the voltage generation circuit 40B. Even in this case, a voltage is generated and supplied.
In FIG. 11, a drug YZ is applied between the diaphragm 11B of the ultrasonic head THB and the skin HF. By pressing skin HF with diaphragm 11B, skin HF at hole 21 of diaphragm 11B rises upward. To the raised portion, a device in which the absorbent cotton DM is gripped by the tip of the vibrator 11C of the ultrasonic head THC is applied. The absorbent cotton DM is impregnated with the drug YZ, and the drug YZ is applied between the vibrating body 11C and the skin HF. The diaphragm 11B and the vibrating body 11C do not come into contact with each other.
[0055]
Therefore, the drug YZ applied to the diaphragm 11B is ionized by the voltage applied to the terminal AB, and transdermal introduction is effectively performed by ultrasonic vibration. In addition, the drug YZ of the absorbent cotton DM applied to the vibrating body 11C is ionized by the voltage applied to the terminal BC at the local portion that is raised inside the hole 21 of the diaphragm 11B. Done effectively. Therefore, by aligning the hole 21 with the portion of the skin HF to be treated, and applying the vibrator 11C thereto, it is possible to locally and efficiently treat the portion.
[0056]
The drug YZ applied to the vibration plate 11B may be different from the drug YZ applied to the vibration body 11C. It may be the same.
The effect of supplying a voltage to the diaphragm 11B and the vibrating body 11C from the terminals B and C, respectively, can also be considered as follows.
[0057]
FIG. 14A shows a state of a current when a voltage is supplied only from the terminal B using only one diaphragm, and FIG. 14B shows a state in which a voltage is supplied from the terminals B and C using two diaphragms. This shows the state of the current when supplied.
[0058]
In FIG. 14A, the speed of the loaded fluid carrier C, that is, the magnitude of the current, is fixed by the voltage, which is the head, and the distance (resistance) at which the gradient is formed. On the other hand, in FIG. 14B, a running gradient is created in the charged fluid carrier C by the voltage V1, and the carrier flows into the potential slope. Even with the same head, the speed is increased by the pushing of the run-in pressure, and the current flows continuously. By controlling the voltages V1 and V2, the current from the diaphragm 11B and the vibrating body 11C can be controlled.
[0059]
The terminals A, B, and C can be configured to output various voltages or currents. For example, there are a DC voltage whose potential decreases in the order of the terminals A, B, and C, a voltage having various switching waveforms, a DC voltage including an AC component, and the like. These may be selected depending on the type of the drug YZ used, the state of ionization, and the like.
[0060]
FIG. 15 shows a block diagram of an example of a voltage generating circuit for supplying such various waveforms of voltage or current.
For example, the following control is performed or a voltage is output by the voltage generation circuit shown in FIG.
(1) The number of pulsating pulses of a velocity waveform such as alternation, pulsating waves, and intermittent intermittent DC is set and arranged in the number of 1 to 31 pulses according to external setting.
(2) In the treatment, the polarity of the positive and negative sliding sweep moving pole and the bioelectric field pole is reversed by external switching between the anode and the cathodic to provide the correct polarity for the treatment purpose.
(3) Efficient selection of the duty ratio and intermittent adjustment and setting for static discharge of the saturation of the medium and the charge and heat accumulation of the living tissue can be performed by adjusting the duty ratio of the duty ratio and the stationary of the duty ratio.
(4) The switching can be changed up to a high frequency pulse frequency range of 3 to 27 KH by selecting and adjusting a DC intermittent cycle.
(5) The cycle width and the frequency are variably set over a wide range.
[0061]
In the above-described embodiment, two ultrasonic heads THB and THC are used, but one ultrasonic head THB may be provided with two types of electrodes. For example, an electrode is provided in the hole 21 of the diaphragm 11B of the ultrasonic head THB via an insulator such as a ceramic material, and a voltage from the terminal C is applied to the electrode. The electrode ultrasonically vibrates together with the diaphragm 11B via an insulator. Electrodes are applied to the local skin HF via the drug YZ to provide ionization of the drug YZ and ultrasonic vibration of the skin HF. In this case, the configuration is simple and the operation is easy.
[0062]
Further, as the drug YZ used for carrying out the method of the present invention, a drug holding material in which a drug YZ is held in a layer of Japanese paper tape and is in a dry state (dry-drug type paper tape). Can be used.
[0063]
In the above embodiment, the shapes and materials of the diaphragms 11, 11B, 11C, the number of the ultrasonic transducers 13, 13B, 13C, the configuration of the ultrasonic heads TH, THB, THC, the drive circuits 30, 30B, 30C and the stimulus The configuration, the number, the driving method, the voltage value, the current value, the waveform, the period, and the like of the voltage generation circuits 40 and 40B can be appropriately changed according to the gist of the present invention.
[0064]
【The invention's effect】
According to the present invention, the penetration of the drug into the skin and the absorption into the blood are efficiently performed by the action of the voltage or the current together with the action of the ultrasonic wave.
[Brief description of the drawings]
FIG. 1 is a view for explaining a method for transdermally introducing a drug according to the present invention.
FIG. 2 is an enlarged view showing a state when an ultrasonic head is applied to the surface of skin.
FIG. 3 is a diagram illustrating the timing of applying ultrasonic vibration and voltage.
FIG. 4 is a front sectional view of the ultrasonic head.
FIG. 5 is an exploded perspective view of the ultrasonic head.
FIG. 6 is a diagram illustrating an example of a drive circuit.
FIG. 7 is a diagram illustrating an example of a stimulation voltage generation circuit.
FIG. 8 is a diagram illustrating an example of a waveform of a voltage including an AC component.
FIG. 9 is a diagram illustrating an example of a voltage waveform including an AC component.
FIG. 10 is a diagram for illustrating a method for transdermally introducing a drug according to the second embodiment of the present invention.
FIG. 11 is an enlarged view showing a state where two ultrasonic heads are applied to the surface of the skin.
FIG. 12 is a circuit diagram illustrating an example of a voltage generation circuit.
FIG. 13 is a diagram illustrating a structure of a bipolar induction method using a voltage generation circuit.
FIG. 14 shows a state of a current when a voltage is supplied from a terminal.
FIG. 15 shows a block diagram of an example of a voltage generation circuit for supplying voltages or currents of various waveforms.
[Explanation of symbols]
1,1B transdermal introduction device
11 diaphragm (vibrator, one electrode)
11B diaphragm (vibrating body)
11C vibrator
30, 30B drive circuit
40, 40B voltage generation circuit
TH, THB, THC ultrasonic head
DK grip electrode (the other electrode)
HF skin
YZ drug

Claims (9)

Applying a metal vibrating body that vibrates by ultrasonic waves to the surface of the skin, and disposing a drug between the vibrating body and the skin,
The vibrating body as one electrode, the drug is ionized by applying a voltage between the other electrode in contact with a site other than the site where the vibrating body is applied,
This allows the ionized drug to penetrate into the skin in a state where the ultrasonic vibration by the vibrator is applied to the skin, based on the vibration electrode method in which the electromagnetic action of the ultrasonic vibration is superimposed.
A method for transdermally introducing a drug, comprising: A first step of maintaining a state in which the ultrasonic vibration and the voltage are applied to the skin by the vibrator for a predetermined time;
Providing a second step of turning off the ultrasonic vibration and the voltage by the vibrating body, and performing an introduction treatment by selectively switching a suitable polarity on the introduction side.
Performing the first step and the second step alternately,
A method for transdermally introducing the drug according to claim 1. Applying a first vibrator made of metal that vibrates by ultrasonic waves to the surface of the skin, and disposing a drug between the first vibrator and the skin,
The first vibrating body is used as one electrode, and the drug is ionized by applying a voltage between the first vibrating body and the other electrode in contact with a part other than the part to which the first vibrating body is applied,
This allows the ionized drug to penetrate into the skin while the ultrasonic vibration by the first vibrator is applied to the skin,
Applying a metal second vibrating body that vibrates by ultrasonic waves to a portion of the skin surface different from the skin surface to which the first vibrating body is applied, and applying the second vibrating body to the skin Place so that there is a drug in between,
The second vibrating body is used as one electrode, and the drug is ionized by applying a voltage between the first vibrating body and the other as the other electrode,
This allows the ionized drug to penetrate into the skin while the ultrasonic vibration by the second vibrator is applied to the skin,
A method for transdermally introducing a drug, comprising: Applying a first vibrator made of metal vibrating by ultrasonic waves to the surface of the skin, and disposing a drug between the first vibrator and the skin;
The first vibrating body is used as one electrode, and a first voltage is applied between the first vibrating body and the other electrode in contact with a part other than the part to which the first vibrating body is applied,
Applying a metal second vibrating body that vibrates by ultrasonic waves to a portion of the skin surface different from the skin surface to which the first vibrating body is applied, and applying the second vibrating body to the skin Place so that there is a drug in between,
Applying a second voltage between the first vibrator and the second vibrator;
A method for transdermally introducing a drug, comprising: The first voltage is a voltage at which the first vibrator is negative and the electrode is positive,
The second voltage is a voltage at which the second vibrator is negative and the first vibrator is positive.
A method for transdermally introducing the drug according to claim 4. The first vibrator is plate-shaped and provided with a hole, and the second vibrator is disposed in the hole.
A method for transdermally introducing the drug according to claim 4 or 5. A first vibrator made of metal that vibrates with an ultrasonic wave for application to the surface of the skin;
A metal second vibrator that vibrates with ultrasonic waves for application to a surface of the skin different from the first vibrator;
An electrode member;
A voltage generation circuit for applying a voltage between the first vibrating body and the electrode member, and between the second vibrating body and the first vibrating body,
A transdermal drug delivery system, comprising: The first vibrator has a plate shape and is provided with a hole, and the second vibrator has a shape capable of being arranged in the hole.
The transdermal drug delivery system according to claim 7. A drug holding material applied between a vibrating body that vibrates with ultrasonic waves and the surface of the skin,
A drug holding material characterized in that a drug is held in a layer of Japanese paper paper tape and is dried.

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