JPH0966111A - Power supply device for iontophoresis and its electric current control method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To reduce the influence of individual differences of impedance of skin or mucosa by an easy constitution, by providing an electric current detecting part in which the difference between an applied electric current value and a discharged electric current value is measured as an active current value, a feedback control part by which the active current value is controlled by making an amplitude of pulse voltage variable. SOLUTION: Medication of a set amount of a drug is initiated by setting an active current value on a medication site by setting a standard voltage of a standard voltage generating part 4, and setting frequency of an oscillating circuit 6, a duty ratio, and electricity supplying duration of pulse voltage. Then, the active current value is measured by an electric current detecting circuit part 9, is electric current /voltage-converted by means of a voltage converting circuit part 10, the electric-current/voltage-converted active voltage value is inputted into a voltage control part 5, and feedback control is performed in the voltage control part 5. A depolarizing circuit part 8 detects the last/first transition of the pulse voltage which is outputted from the oscillating circuit part 6, and is turn on/off automatically, and electricity is discharged between a related conductor and a non-related conductor through a resistant body and thereby, the polarized potential is depolarized when the depolarizing circuit part is turned on.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a power supply device for iontophoresis for stably delivering a physiologically active substance into a living body from a percutaneous or transmucosal membrane, and a current control method thereof.

[0002]

2. Description of the Related Art In recent years, iontophoresis utilizing electric driving force has been studied as a method for promoting absorption of a drug from the skin or mucous membrane into the living body. In iontophoresis, a conductor having an electrode containing a drug storage layer and a non-conductor having a counter electrode not containing a drug are attached to the skin or mucous membrane, and current is applied between the electrodes to absorb the drug into the body. It promotes. There are two types of energization: constant current type energization that keeps the power consumption of the entire circuit including skin and mucous membrane constant, and constant voltage type energization that keeps the voltage applied to the entire circuit constant. There is. As the energization method, an energization method using direct current or pulse is adopted. The equivalent circuit of skin will be described below. FIG. 8 is an equivalent circuit showing the skin electrically. R1 is ohmic resistance, R2 is polarization resistance, C
Is the polarization capacity. In the case of direct current or pulse, the current flows through the ohmic resistance R1 and the polarization resistance R2 or is accumulated in the polarization capacitance C at the initial stage of energization, but when the current is accumulated in the polarization capacitance C,
After that, almost no current flows through the ohmic resistor R1. That is, a current substantially equal to the applied current flows between the skins. Since the electric current flowing between the skin and the permeation amount of the drug have a proportional relationship, the permeation amount of the drug can be predicted to some extent from the applied current value. However, when the polarization capacity C is charged, the energization method using direct current or pulse cannot apply a high current because electrical current is concentrated on the ohmic resistance R1 and electrical stimulation is generated on the skin and mucous membrane. There is a problem that the dose of the drug is also limited. Further, by using a pulse, by setting the duty ratio of the pulse such that the effective application time of the pulse is shortened and the off time of the pulse is lengthened, the polarization capacitance C
Although there is a method of sufficiently discharging the electric charge stored in the medicine, it has a problem that the medicine administration time is long and it does not work effectively. Therefore, various methods of improving electrical stimulation and smoothly administering a drug have been studied. For example, there are pulse depolarization energization methods shown in Japanese Patent Publication No. 2-45461, Japanese Patent Publication No. 3-49589, and Japanese Patent Publication No. 4-1634. In this energizing method, the current accumulated in the polarization capacitor C is discharged by short-circuiting the conductor and the indifferent conductor in the pulse application rest period for each pulse. Therefore, the skin circuit returns to the initial state, and the next pulse current flows through the ohmic resistance R1, the polarization resistance R2, and the polarization capacitance C again. Therefore, electrical stimulation to the skin or mucous membrane can be reduced. In this energization method, a part of the loaded current flows through the resistors R1 and R2, but the remaining current is charged / discharged in the polarization capacity C of the skin or mucous membrane. The current measurement when pulse depolarizing current is applied to the skin using the conventional power supply for iontophoresis will be described below. FIG. 9 is a measurement schematic diagram of current detection in a conventional constant current control type pulse depolarization type power supply for iontophoresis. A
1, A2 is an ammeter for measuring the current flowing in the living body, SW
Is a switch for performing pulse depolarization. In the conventional pulse depolarization, an ammeter is arranged at either A1 or A2 to measure the current flowing during energization. During energization, the load current value (applied current value), which is the sum of the current value of the charge stored in the polarization capacitor C and the current value flowing through the ohmic resistance R1 and the polarization resistance R2, was measured. At the time of a short circuit, the electric charge accumulated in the polarization capacitor C is discharged, and a small amount of the current flows into the ohmic resistance R1 and the polarization resistance R2, but most of it is discharged through the switch SW on the power supply side. Conventionally, the load current value measured at the time of energization controls the amount of energization flowing in the living body to control the drug delivery amount.

[0003]

However, in the above-described conventional power supply device for iontophoresis using pulse depolarization energization, the polarization capacitance C, the ohmic resistance R1, and the polarization resistance R2 vary from individual to individual, and the values vary. Because of the difference, in the energization by pulse depolarization, even if the same load current was passed, the current for effectively administering the drug was different, and the drug delivery amount could not be accurately predicted from the load current. That is, in the past, the drug delivery amount was predicted by a constant current measurement value such as a load current, but in reality, the drug delivery amount absorbed by each individual is different, and there is a problem in that there is variation and lack of reliability. Had. In addition, there is a problem in that when the treatment is performed regularly, the variations are overlapped, and the drug delivery amount and the treatment effect are different from each other, which is extremely unreliable. In particular, it is necessary to be extremely careful when administering a drug with a blood concentration close to the therapeutic range and a toxicity range (such as a drug with a narrow therapeutic window), because the drug delivery amount cannot be accurately determined. I had a problem.

The present invention solves the above-mentioned problems of the prior art, has a simple device construction, reduces the influence of individual differences in impedance of the skin and mucous membranes, and smoothes a certain amount of physiologically active substance into the living body. Iontophoresis power supply with excellent pharmacological effect, safety, reliability and mass productivity, and reduce the influence of individual difference of impedance of skin and mucous membrane, and put a certain amount of physiologically active substance in the body. An object of the present invention is to provide a current control method for a power supply device for iontophoresis, which is smoothly delivered and has an excellent pharmacological effect.

[0005]

In order to achieve this object, a power supply device for iontophoresis according to claim 1 of the present invention comprises a gate conductor and a non-gate conductor, and a gate conductor. A pulse depolarization type iontophoresis power supply device for applying a pulse voltage / current between a living body and an indifferent conductor,
When the pulse voltage / current is applied, the applied current value flowing between the gate and the indifferent conductor and when the pulse voltage / current is stopped, the gate and the indifferent conductor are short-circuited and charged in the living body. And a feedback control unit that controls the active current value by varying the amplitude of the pulse voltage. ing. The power supply device for iontophoresis according to claim 2 is the power supply device for iontophoresis according to claim 1, wherein the current detection unit converts the effective current value into an effective voltage value, and the feedback control unit changes the pulse voltage / current according to the effective voltage value. It has a configuration for performing feedback control on the amplitude of. The power supply device for iontophoresis according to claim 3 is the power supply device for iontophoresis according to claim 2, wherein the current detector includes a smoothing resistor that smoothes the effective voltage value converted from the effective current value to a substantially constant value. have. The iontophoresis power supply device according to claim 4 is the power supply device for iontophoresis according to any one of claims 1 to 3, wherein the feedback control unit variably controls a pulse cycle of the pulse voltage / current or a pulse duty ratio. are doing. The power supply device for iontophoresis according to claim 5 is the power supply device for iontophoresis according to any one of claims 1 to 4, wherein a resistor is provided between the gate conductor and the non-gate conductor when application of a pulse voltage / current is stopped. It has a configuration including a depolarizing circuit portion that short-circuits via the. The current control method for a power supply device for iontophoresis according to claim 6, comprising a gate conductor and a non-gate conductor, and a pulse voltage / current in the living body between the gate conductor and the non-hall conductor. A method for controlling a current of a pulse depolarization type iontophoresis power supply device for applying a pulse voltage, comprising: an applied current value flowing between a gate conductor and an indifferent conductor when a pulse voltage / current is applied; Effective current measuring step of measuring the difference between the discharge current value at which the electric charge charged in the living body is discharged by short-circuiting the conductor and the indifferent conductor when the current application is stopped, and the pulse voltage And a feedback control step for controlling the effective current value by changing the amplitude of the.

Here, the effective current is the value of the applied current flowing in the living body between the gate conductor and the non-barrel conductor when the pulse voltage / current is applied, and the gate conductor when the pulse voltage / current application is stopped. And the indifferent conductor are short-circuited, and the difference between the discharge current value at which the charge charged in the polarization capacitance C in the living body is discharged is defined as the effective current value. That is, the applied current value is the sum of the charging current value stored in the polarization capacitance C in the living body and the effective current value flowing through the ohmic resistance R1 and the polarization resistance R2 when the pulse voltage / current is applied. The discharge current value is the ohmic resistance R1,
Although there is a current flowing to the polarization resistor R2, it is extremely small, and most of the current is discharged through the switch SW on the power supply side. In short, all of the applied current value Im that is the applied current is not an effective current flowing in the living body between the skin,
The effective current Ie that effectively flows in the living body is Ie = Im-I
It can be represented as c. However, Ic is a charging current value with which the polarization capacitance C is charged. Therefore, the effective current value Ie
By measuring, it is possible to reduce variations due to individual differences, and actually measure the drug arrival amount in the living body with high accuracy.

[0007] Examples of physiologically active substances used in the power supply for iontophoresis include morphine, fentanyl,
Central analgesics such as pethidine, codeine, buprenorphine, butorphanol, eptazocine, pentazocine and insulin, calcitonin, calcitonin-related gene peptides, vasopressin, desmopressin, protyrelin (TRH), adrenocorticotropic hormone (ACTH),
Luteinizing hormone releasing factor (LH-RH), growth hormone releasing hormone (GRH), nerve growth factor (NGF) and other releasing factors, angiotensin (angiotensin), parathyroid hormone (PTH), thyroid stimulating hormone (TSH, Thyrotropin), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, serum gonadotropin, placental gonadotropin (HCG), growth hormone, somatostatin, somatomedin, glucagon, oxytocin, gastrin, secretin , Endorphin, enkephalin, endothelin, cholestokinin, neurotensin, interferon, interleukin, transferrin, erythropoietin, superoxide desmutase (SO
D), granulocyte stimulating factor (G-CSF), vasoactive intestinal polypeptide (VIP), muramyl dipeptide, corticotropin, urogastrone, hA
Peptides such as NP, carmazepine, chlorpromazine, diazepam, tranquilizers such as nitrazepam, pleomycin, adreamycin, 5-fluorouracil,
Antineoplastic drugs such as mitomycin, digitalis, digoxin, cardiotonics such as digitoxin, estradiol,
Sex hormones such as testosterone, reserpine, clonidine and other antihypertensive agents are considered, but not limited thereto.

As the power source of the power supply for iontophoresis, manganese dry batteries, alkaline dry batteries, lithium batteries, unicad batteries, silver oxide batteries, mercury batteries, air batteries, alkaline manganese batteries, plastic batteries, etc., and buttons for them. A button-shaped battery or a sheet-shaped battery processed into a sheet shape or a paper shape is preferably used.

The feedback control section of the iontophoresis power supply device converts the effective current value measured in the current detection circuit section into a voltage based on a reference voltage set using the voltage from the power supply section. Feedback control is performed by controlling the voltage to the inside of the living body to control the effective current flowing in the living body to be substantially constant. Further, by variably controlling the reference voltage using a CPU (central processing unit) or the like, it is possible to control the reference voltage according to the difference in the drug or individual capacity, resistance value, symptom, etc., which is extremely effective. An oscillator circuit unit that performs pulse oscillation is used as the pulse modulation of the voltage of the output circuit, and the effective current value can also be controlled by changing and controlling the pulse period or the duty ratio of the pulse. Further, the pulse oscillator may be provided with an output limiting circuit for limiting a large peak current flowing through the human body when the pulse voltage rises and falls.

The switch used in the depolarization circuit section is for removing the polarization potential generated in the living body such as the skin by pulse depolarization when the application of the pulse voltage / current is stopped, and a transistor switch such as an FET switch is used. Used. As the resistor used in the depolarizing circuit part, a resistor having a low resistance value is used which measures a current value by voltage conversion.

The effective current value of the power supply for iontophoresis is usually 0.01 to 10 mA / cm ² , preferably 0.05 to 1 mA / cm ² , and the voltage is the skin and the conductor or the barrier. Depending on the contact area with the conductor, it is about 1 to 20V, preferably 3 to 12V. This makes it possible to effectively inject the drug into the living body while suppressing the pain caused by the electric current passed through the living body.

The material of the electrodes used for the conductor and the non-conductor is not particularly limited, but for example, platinum, titanium, carbon or the like of the polarizable electrode can be used, and the material of the non-polarizable electrode can be used. You may use silver / silver chloride etc.

With this configuration, the applied current value flowing between the gate and the indifferent conductor when the pulse voltage / current is applied and the gate and the indifferent conductor are short-circuited when the pulse voltage / current application is stopped. A current detection unit that measures the difference between the discharge current value at which the electric charge charged in the living body is discharged as an effective current value, a feedback control unit that controls the effective current value by varying the amplitude of the pulse voltage, With the above, the measurement of the effective current value can be grasped as the current value flowing in the living body very accurately, and the feedback control unit significantly reduces the individual difference in the drug delivery amount. In particular, since a preset drug delivery amount can be accurately controlled, it is possible to safely and effectively administer a physiologically active substance, the pharmacological effect can be remarkably improved, and the drug delivery amount can be accurately controlled. It is possible to realize various drug administrations. Especially,
When administering a drug having a blood concentration near a therapeutic range and a toxicity range (a drug having a narrow therapeutic window, etc.), the drug delivery amount can be accurately grasped, and safety and reliability can be improved. In addition, since the pulse depolarization type can significantly reduce electrical stimulation to the skin and mucous membranes, the drug can be effectively administered. Furthermore, the current detection unit converts the effective current value into an effective voltage value, and the feedback control unit provides feedback to the amplitude of the pulse voltage / current according to the effective voltage value, so that voltage comparison by generating a reference voltage is possible, The circuit configuration is extremely simple, and the device can be downsized. Since the current detection unit includes a smoothing circuit that smoothes the effective voltage value obtained by converting the effective current value to a substantially constant value, in the feedback control, when using a comparator or the like, the active voltage value is constantly compared. Stable feedback control can be performed, local fluctuations such as the amplitude of the pulse voltage are small, and electrical stimulation to the skin and mucous membrane can be significantly reduced. The feedback control unit variably controls the pulse amplitude of the pulse voltage, the pulse period, or the pulse duty ratio to control the time for charging the polarization capacitor C during energization and the time for discharging the charge accumulated in the polarization capacitor C during the suspension of application. It can be optimized according to the size of the polarization capacity C in the living body, the accuracy of measuring the effective current can be suppressed within a predetermined range, the drug delivery amount can be accurately measured, and the safety and reliability can be improved. Therefore, the drug delivery amount can be improved and the drug delivery amount can be quickly controlled. Converting the current flowing through the resistor into a voltage by providing a depolarizing circuit that short-circuits the gate conductor and the non-barrel conductor via the resistor when the pulse voltage / current is not applied. And the circuit can be easily configured,
It is possible to reduce the size of the device. When the pulse voltage / current is applied, the applied current value flowing between the gate and the indifferent conductor and when the pulse voltage / current is stopped, the gate and the indifferent conductor are short-circuited and charged in the living body. By including a current detection step of measuring the difference between the discharge current value at which the electric charge is discharged as an active current value, and a feedback control step of controlling the active current value by varying the amplitude of the pulse voltage, Since the preset drug delivery amount can be accurately controlled, it is possible to safely and effectively administer a physiologically active substance, the pharmacological effect can be remarkably improved, and the drug delivery amount can be accurately controlled. Administration can be achieved.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is a block circuit diagram showing the configuration of an active current control type pulse depolarization type power supply for iontophoresis in one embodiment of the present invention. 1 is an active current control type pulse depolarization type iontophoresis power supply device of one embodiment of the present invention,
When the pulse voltage is applied, the applied current value flowing between the gate and the indifferent conductor and the charge charged in the living body due to the short circuit between the gate and the indifferent conductor when the pulse voltage is stopped. The effective current value, which is the difference from the discharge current value to be discharged, is measured, and the amplitude of the pulse voltage is varied to perform feedback control so that the effective current value is substantially constant. Reference numeral 2 is a power supply unit composed of a small battery such as a coin battery or a button battery for applying a voltage between the electrodes of the gate conductor and the non-gate conductor, and 3 is a voltage booster for the power supply unit 2 if necessary, which is equal to or higher than the power supply voltage. To obtain an output of the reference voltage generator 4, a reference voltage generator 5 for controlling the active current value to a substantially constant value, and a voltage controller 5 which is a feedback controller. Voltage value is input to the output circuit unit 7 described later based on the voltage value set by the reference voltage generation unit 4, and the effective current value is within the range of 70% to 150% of the set value. Feedback control is automatically performed so that Reference numeral 6 denotes an oscillation circuit unit that pulse-modulates the voltage supplied from the booster circuit unit 3 into a pulse voltage of about 1 kHz to 100 kHz, and the pulse frequency and pulse duty ratio can be changed. Reference numeral 7 is an output circuit section that performs switching according to the frequency and pulse duty ratio from the oscillation circuit section 6 and outputs the voltage value output from the voltage control section 5 as a pulse voltage, and 8 is a pulse voltage output from the oscillation circuit section 6. It is a depolarization circuit part that has a switch part that depolarizes the polarization potentials of the gate conductor and the indifferent conductor by short-circuiting between the gate conductor and the indifferent conductor via the resistor at the same time when the application is stopped. . Reference numeral 9 is a current detection circuit unit that measures the value of the effective current flowing in the living body, and 10 is a voltage conversion circuit unit that converts the effective current value measured by the current detection circuit unit 9 into an effective voltage value. Reference numeral 11 denotes a display unit that displays the effective voltage value converted by the voltage conversion circuit unit 10, reference numeral 12 denotes an output terminal that is connected to the conductor and outputs a pulse voltage to the load, 1
An output terminal 3 is paired with the output terminal 12 and is connected to the indifferent conductor. In the present embodiment, the active current value is controlled by converting the active current value measured by the current detection circuit unit 9 into a current / voltage in the voltage conversion circuit unit 10 and performing feedback control to the voltage control unit 5 to bring it into the living body. However, in some cases, the voltage value or the like correlated with the active current value is fed back to the oscillation circuit unit 6, and the pulse frequency and the pulse duty are varied in the oscillation circuit unit 6 for energization. It can also be done by controlling the time.

The operation of the active current control type pulse depolarization type iontophoresis power supply device of the present embodiment having the above-described configuration will be described below. First, the sekiko and the non-sekiko are attached to the administration site of the human body. The drug storage layer is built in the conductor at the administration site. Next, the main power source of the iontophoresis power supply device 1 is turned on. next,
The effective current value flowing through the administration site is set by setting the reference voltage of the reference voltage generation unit 4 according to the condition of the drug, the patient, etc., and the physical condition. Next, the frequency and duty ratio of the oscillation circuit unit 6 and the energization time of the pulse voltage are set, and administration of the designed dose is started. Here, in the active current measuring step, the active current value is measured in the current detection circuit unit 9 and the current / voltage is converted in the voltage conversion circuit unit 10. Next, as a feedback control step,
The effective voltage value that is current / voltage converted by the voltage conversion circuit unit 10 is input to the voltage control unit 5 and feedback control is performed by the voltage control unit 5 to control the effective current value to a predetermined value to thereby obtain a predetermined drug. The dose of is controlled. After administration,
The pulse output voltage of the power supply device 1 for iontophoresis is automatically cut off, and the treatment is ended by separating the conductor and indifferent conductor from the administration site. During administration, the depolarization circuit unit 8 is automatically turned on / off by detecting the falling / rising of the pulse voltage output from the oscillation circuit unit 6, and when the depolarization circuit unit 8 is turned on, The polarization potential is depolarized by discharging between the and the indifferent conductor through the resistor. Next, the measurement position of the current detection unit 9 of the power supply device for iontophoresis in one embodiment of the present invention will be described below with reference to FIG. FIG. 2 is a current measurement diagram of the current detector of the power supply device for iontophoresis according to the embodiment of the present invention.

In FIG. 2, A1, A2, A3, A4
A5 is a current detection unit capable of measuring an effective current value in the living body,
SW is a switch for performing pulse depolarization. The switch SW is connected to A when energized, and is connected to B when depolarized. The currents are measured by the current detectors A1 and A3 or A2 and A3 to calculate the effective current, or the effective current value is measured at A4 or A5. In particular, by measuring with the A4 or A5 current detecting unit, it is possible to configure the current detecting unit with one, and the device can be extremely simplified, and downsizing can be realized. Hereinafter, the voltage and current waveforms of the output terminal 12 of the power supply device for iontophoresis in one embodiment of the present invention will be described. 3A is an output voltage waveform diagram of an output terminal of the iontophoresis power supply device according to the embodiment of the present invention, and FIG. 3B is a current waveform diagram of the output terminal. In FIG. 3B, the area A is the applied current value flowing in the living body when the pulse voltage is applied, and the area B is the discharge current accumulated in the polarization capacitance C discharged in the pulse depolarization. It is a value. The difference between the applied current value of A and the discharge current value of B is the effective current value. By controlling this effective current value, the preset drug delivery amount can be accurately controlled, and safe and effective physiological activity can be achieved. It makes it possible to administer the substance and can significantly improve the pharmacological effect.

[0017]

An embodiment of the present invention will be described below with reference to the drawings. FIG. 4 is a circuit diagram of an active current control type pulse depolarization type power supply for iontophoresis according to one embodiment of the present invention. Here, FIG. 4 is a circuit diagram specifically showing the block diagram of FIG. Reference numeral 21 is a circuit power supply battery which is the power supply unit 2, 22 is a power supply smoothing capacitor, 2
Reference numeral 3 is a current limiting resistor for generating a reference voltage, 24 is a Zener diode for generating a reference voltage which is the reference voltage generating unit 4, 25 is a voltage comparison comparator for performing voltage control, and 26 and 27 are booster circuits. A voltage doubler generating diode that configures the unit 3 and boosts the voltage of the circuit power supply battery 21, and 28 is an oscillator circuit that includes the oscillator circuit unit 6 using an inverter, a resistor, and a capacitor. , The duty ratio of the pulse voltage is determined. 29 and 30 are output control transistors that configure the voltage control unit 5 that controls the amplitude of the pulse voltage applied to the living body based on the output voltage from the voltage comparison comparator 25, and 31 and 32 are output control transistor voltages. 29,
It is a pulse output transistor that constitutes the output circuit unit 7 that switches the voltage controlled by 30 or the like to a pulse and applies the pulse voltage to the living body. Reference numeral 33 is a depolarizing transistor that constitutes the depolarizing circuit unit 8 that performs pulse depolarization. Reference numeral 34 is a load inside the living body that administers the drug, 35 is a resistance for current / voltage conversion for measuring an effective current value as a voltage, 36 is an effective current measuring capacitor for accumulating and measuring an effective current, and 37 is effective It is a smoothing resistor that smoothes the effective voltage value charged and discharged in the current measuring capacitor 36 to a substantially constant value, and forms a smoothing circuit together with the effective current measuring capacitor 36 and the current / voltage converting resistor 35. Here, the effective voltage value of the active current measuring capacitor 36 is input to the voltage comparison comparator 25. Thus, the active current value is feedback-controlled to the output voltage by comparing the reference voltage value by the Zener diode 24 and the active voltage value by the active current measuring capacitor 36, and the active current value is controlled to be substantially constant.

The voltage / current waveforms observed in the circuit diagram of the effective current control type pulse depolarization type iontophoresis power supply device of the embodiment of the present invention constructed as above will be described below. . 5A is a voltage waveform diagram at point A in the circuit diagram (FIG. 4) of the iontophoresis power supply device according to the embodiment of the present invention.
5 (b) is a current waveform diagram at point A, and FIG. 5 (c) is B
FIG. 5D is a voltage waveform diagram at a point, and FIG. 5D is a voltage waveform diagram at a point C. Thus, the voltage waveform at point C is
The effective voltage value is measured to be substantially constant by the smoothing resistor.
The active current control type pulse depolarizing iontophoresis power supply device and the conventional constant current control pulse depolarizing iontophoresis power supply device of one embodiment of the present invention configured as described above are as follows. Iontophoresis of calcitonin was administered, and a comparative experiment was conducted on the serum concentration of calcitonin.

(Experimental Example) Using the active current control type pulse depolarization iontophoresis device of the embodiment, energization was performed for 2 hours so that the effective current was substantially constant at 0.7 mA. Three beagle dogs (body weight: about 10 kg) were anesthetized with sodium pentobarbital, and then salmon calcitonin was administered by iontophoresis. The administered derivative (+ electrode) preparation was composed of a silver electrode, a drug holding membrane, a non-woven fabric, and a cation exchange membrane, and contained salmon calcitonin (250 units) on the drug holding membrane. This Kanko side preparation was administered to the oral cavity of dogs. On the other hand, a non-inclusion side preparation comprising a silver / silver chloride electrode and polyvinyl alcohol containing salt was applied to the dog's ear. After conducting effective current-controlled pulse depolarization with an iontophoresis device, blood was sampled over time, and salmon calcitonin concentration in serum was measured with a commercially available radioimmunoassay kit. FIG. 6 shows the measurement results.
Here, the measurement data shows a change in salmon calcitonin concentration value in serum up to 3 hours in a non-energized state after being energized for 2 hours.

(Comparative Example) As a comparative example, a constant current (constant current control type pulse depolarization iontophoresis device was used instead of the effective current control type pulse depolarization type iontophoresis power supply device of the experimental example). The electric current was applied for 2 hours at 1.5 mA), and the maximum serum concentration of calcitonin (0.5 hours at any individual) was measured. The measurement result is shown in FIG. As is apparent from FIGS. 6 and 7, in the experimental example, the highest serum concentration (0.5 hours in any individual) was 860 pg / ml in the highest individual and 691 pg / ml (780 ± 49 in the lowest individual). (Mean ± SE (variance), n (number of samples) = 3)) and the difference is about 1.2
The individual difference was extremely small. Regarding the salmon calcitonin concentration in serum at other times, the difference between individuals was extremely small as shown in FIG. On the other hand, when electricity was applied by the conventional constant current method (1.5 mA) of the comparative example, as shown in FIG. 7, the highest serum concentration (0.5 hours in any individual) was 1059 pg / ml,
The lowest individual had an extremely large individual difference of 95 pg / ml (525 ± 283 (mean ± SE, n = 3)), which was 10 times or more. From this, the effective current control type pulse depolarization type iontophoresis device reduces individual difference in absorption of physiologically active substance as compared with the conventional constant current control type pulse depolarization type iontophoresis device. It proved to be extremely effective as a method. As described above, according to this example, the measurement of the effective current value is grasped as the current value flowing in the living body very accurately, and the feedback control unit significantly reduces the individual difference in the drug delivery amount, and the preset drug Since the delivery amount can be reliably controlled, it is possible to safely and effectively administer the physiologically active substance, so that the pharmacological effect can be remarkably improved.

[0021]

As described above, according to the present invention, a current detector for measuring an effective current value flowing between a gate and a gate.
Since the feedback control unit that controls the effective current value by varying the amplitude of the pulse voltage is provided, the individual difference in the drug delivery amount can be significantly reduced, and the preset drug delivery amount can be reliably controlled, which is safe and effective. It is possible to provide a power supply device for iontophoresis having a superior pharmacological effect by administering a physiologically active substance to the. In particular, for the administration of drugs with a blood concentration near the therapeutic range and toxicity range (drugs with a narrow therapeutic window, etc.), it is possible to accurately grasp the drug delivery amount, and a highly safe power supply for iontophoresis. Can be realized. Further, the configuration of the device is simple, downsizing can be realized, and an iontophoresis power supply device excellent in mass productivity can be realized. Since the current detection step of measuring the effective current value flowing between the gate conductor and the non-barrel element and the feedback control step of controlling the active current value by varying the amplitude of the pulse voltage are provided, drug delivery is achieved. It is possible to accurately grasp the amount and to realize a current control method for the iontophoresis power supply device having an excellent pharmacological effect.

[Brief description of drawings]

FIG. 1 is a block circuit diagram showing a configuration of an active current control type pulse depolarization type iontophoresis power supply device according to an embodiment of the present invention.

FIG. 2 is a schematic diagram of current measurement of a current detection unit of an active current control type pulse depolarization type iontophoresis power supply device according to an embodiment of the present invention.

FIG. 3A is a voltage waveform diagram at the output terminal of the active current control type pulse depolarization type power supply for iontophoresis in one embodiment of the present invention. FIG. 3B is the active current control in one embodiment of the present invention. Waveform diagram at the output terminal of the pulse-depolarized iontophoresis power supply

FIG. 4 is a circuit diagram showing a configuration example of an active current control type pulse depolarization type iontophoresis power supply device in one embodiment of the present invention.

5A is a voltage waveform diagram at point A in the circuit diagram of the active current control type pulse depolarization type iontophoresis power supply device in one embodiment of the present invention. FIG. 5B is one embodiment of the present invention. Current waveform diagram at point A in the circuit diagram of the active current control type pulse depolarization type iontophoresis power supply device in (c) Active current control type pulse depolarization type iontophoresis in one embodiment of the present invention Voltage waveform diagram at point B in the circuit diagram of the cis power supply device (d) Voltage at point C in the circuit diagram of the active current control type pulse depolarization type iontophoresis power supply device in one embodiment of the present invention Waveform diagram

FIG. 6 is a serum concentration of calcitonin measured using an effective current control type pulse depolarization type iontophoresis power supply device in Experimental Example 1.

FIG. 7: Calcitonin serum concentration measured using a constant current controlled pulse depolarization type iontophoresis power supply device in Comparative Example 1

FIG. 8 is an equivalent circuit showing the skin electrically.

FIG. 9 is a schematic diagram of measurement of current detection in a conventional constant current control type pulse depolarization type iontophoresis power supply device.

[Explanation of symbols]

1 Power Supply Device for Iontophoresis of One Embodiment of the Present Invention 2 Power Supply Section 3 Booster Circuit Section 4 Reference Voltage Generation Section 5 Voltage Control Section (Feedback Control Section) 6 Oscillation Circuit Section 7 Output Circuit Section 8 Depolarization Circuit Section ( Switch section 9 Current detection circuit section 10 Voltage conversion circuit section 11 Display section 12, 13 Output terminal 21 Circuit power supply battery 22 Power supply smoothing capacitor 23 Current limiting resistor 24 Zener diode 25 Voltage comparison comparator 26, 27 times voltage generation Diode 28 Oscillation circuit 29, 30 Output control transistor 31, 32 Pulse output transistor 33 Depolarization transistor 34 Load 35 Current / voltage conversion resistor 36 Active current measurement capacitor 37 Smoothing resistor

Claims (6)

[Claims] 1. A pulse depolarization type iontophoresis device comprising a gate conductor and a gate conductor, wherein a pulse voltage / current is applied in the living body between the gate conductor and the gate barrier. A power supply device, comprising: an applied current value flowing between the gate and the indifferent conductor when the pulse voltage / current is applied; and the barrier and the barrier when the pulse voltage / current is stopped. A current detector that measures the difference between the discharge current value at which the charge charged in the living body is discharged by short-circuiting with the conductor as an effective current value, and the effective current value by varying the amplitude of the pulse voltage. A power supply device for iontophoresis, comprising: a feedback control unit for controlling the. 2. The current detection unit converts the effective current value into an effective voltage value, and the feedback control unit performs feedback control on the amplitude of the pulse voltage / current based on the effective voltage value. The power supply device for iontophoresis according to claim 1. 3. The iontophoresis device according to claim 2, wherein the current detection unit includes a smoothing resistor that smoothes the effective voltage value obtained by converting the effective current value to a substantially constant value. Power supply for lathes. 4. The iontophoresis according to claim 1, wherein the feedback control unit variably controls a pulse cycle or a pulse duty ratio of the pulse voltage / current. Power supply. 5. A depolarizing circuit unit for short-circuiting the pulse voltage / current through a resistor when the application of the pulse voltage / current is stopped is provided between the gate conductor and the indifferent conductor. 1
5. The power supply device for iontophoresis according to any one of 1 to 4. 6. A pulse depolarization type iontophoresis, comprising a gate conductor and a non-gate conductor, and applying a pulse voltage / current in the living body between the gate conductor and the gate conductor. A method for controlling a current of a power supply device for a power supply, comprising: an applied current value flowing between the gate conductor and the indifferent conductor when the pulse voltage / current is applied; Active current measurement step of measuring the difference between the discharge current value at which the charge charged in the living body is discharged by short-circuiting the child and the indifferent conductor, and the amplitude of the pulse voltage is varied. And a feedback control step of controlling the effective current value. The current control method of the power supply device for iontophoresis, comprising: