JP3761201B6 - Device for iontophoresis - Google Patents

Description

表１（１）で示すようにデューティ比を上げることにより、有効電流（Ｉｅ）が上昇すると同時に被験者も次第に強く刺激を感じる様になるがデューティ比７５％、有効電流１．３（ｍＡ）で不感状態となった。出力電圧を１２Ｖとして同様のことを行った所、表１の（２）で示すようにデューティ比７５％、有効電流１．３６（ｍＡ）で９（Ｖ）の出力電圧の時と同様、被験者は刺激を感じることがなく、やはり不感状態となった。この様に不感状態であるにも拘らず投薬効率に直接影響を与える有効電流が、非常に増加していることが示されている。
【００１１】
【発明の効果】
上述した通り、本発明は周波数１ＫＨｚ〜１００ＫＨｚ、デューティ比を５５％〜８５％とした脱分極パルスを出力することによって痛みが無い状態あるいは、不感状態で充分な投薬効率を上げることができる等の効果を有する。
【図面の簡単な説明】
【図１】本発明の実施例を示す図。
【図３】本発明の実施例を示す図。
【図２】図１の動作を説明する為の図。
【図４】図３の動作を説明する為の図。
【符号の説明】
１ パルス出力手段
２ デューティ可変手段
３ 入力手段
４ 脱分極パルス生成手段
５ 出力端
６ マイクロコンピュータ[0001]
[Industrial application fields]
The present invention relates to a device for iontophoresis.
[0002]
[Prior art]
Iontophoresis (iontophoresis) has been gaining increasing attention recently as an effective topical dosage method that promotes transdermal absorption of ionic drugs (Glass JM et al., International Journal of Dermatology (Glass JM et al , Int. J. Dermatol.) 19 519 (1980); Russo J., American Journal of Hospital Pharmacy (Russo J., Am. J. Hosp. Pharm.) 37 843 (1980); Gangarasa Elpe et al., Journal Of Pharmacologic Experiment and Therapy (Gangarosa LPet al., J. Pharmacol. Exp. Ther.) 212 377 (1980); Kwanbies et al., Journal of Infectious Dishes (Kwon BS et al., J. Infect. Dis. 140 1014 (1979); Hill JM et al., Annual of New York Academic of Science (Hill JM et al., Ann. NY. Acad. Sci.) 284 604 (1977); Tannebaum M., Phys. Ther. 60 792 (1980) and Earl. Etch Guy Hen Advanced Drug Delivery Reviews 9 (1992) 119-607, etc.). In the iontophoresis in these prior arts, normally, an output terminal of a continuous flat flow generator or an intermittent flat flow generator, a conductor formed by covering a conductor such as a metal plate with a liquid impregnated absorbent cotton, and the like are used. Since it is made by connecting an indifferent conductor, its implementation is quite complicated, and although its administration method is extremely effective, its spread has to be limited. However, recently, it has been disclosed that transcutaneous medication without burns can be performed by using pulse output means having a depolarization function as electrical output for medication (Japanese Patent Laid-Open No. Sho 156475). . However, there are still parts that have not been elucidated in various aspects, such as the relationship between electrical output and dosing efficiency.
[0003]
[Means for Solving the Problems]
In view of the above, as a result of intensive research, the present inventors have generated pulse generation means for generating a specific dead zone pulse in a frequency range of about 1 KHz to 100 KHz and a duty ratio in the range of 55 to 85%, and generation of the pulse generation means. Surprisingly, a patient with pain, unpleasant stimulation, by means of an iontophoresis device having a depolarization means for depolarizing between the therapeutic pulse output terminals during the rest of the therapeutic pulse formed on the basis of the pulse Alternatively, the current amount for energization of the living body is dramatically increased without feeling the stimulation itself, and an efficient transdermal medication has been realized.
[0004]
The pulse frequency output by the pulse generation means is set in a range of about 1 KHz to 100 KHz. In other ranges, for example, below about 1 KHz, it is a frequency band used by the low-frequency treatment device, and is a frequency band that is easily felt by the living body. On the other hand, when the frequency is 100 kHz or more, the energy consumption of the circuit itself or the increase in loss resistance due to heat generation of each part becomes remarkable, which is not preferable.
The duty ratio of the pulse output from the pulse generating means is set to a specific dead zone in the range of 55 to 85%. At this value, the patient himself does not feel any pain or unpleasant stimuli even though the pulse is close to direct current. At duty ratios other than this dead zone, as in the case of using direct current, the patient feels grief and uncomfortable feeling and does not reach a state where medication can be performed. Although iontophoresis by direct current is a means that has been studied in the past, it is less practical because burns and pain occur even at low voltages. However, on the other hand, it has been reported that the administration efficiency is good due to the large effective current flowing through the living body.
The duty ratio indicating the dead zone varies slightly depending on the electrode material constituting the conductor. For example, the dead zone when mainly using carbon and titanium as an electrode is between 75 to 80% duty ratio, and the dead zone when Ag / AgCl is used as an electrode is between 60 to 75% duty ratio. Each exists.
Furthermore, since this dead zone may vary slightly depending on the individual, it is useful to further provide a duty ratio adjusting means.
[0005]
The depolarizing means shown in the present invention is typically the one shown in Japanese Patent Laid-Open No. 156475, and is connected to a pair of conductors that form an interface with the skin between pulse intervals during pulse intervals. A circuit provided with a circuit for electrically short-circuiting the output terminals is exemplified.
[0006]
【Example】
(1) is a pulse output means, which comprises a self-excited multivibrator or the like, and outputs pulses having a frequency of 1 (KHz) to 100 (KHz) as described above. The pulse output means (1) may have functions such as frequency adjustment.
(2) is a duty adjustment means, which is composed of a monostable multivibrator or the like, and performs duty adjustment on the input pulse and outputs a pulse having a desired dead zone duty ratio. Further, the duty adjusting means (2) is provided with an input means (3) for performing an input for adjusting the duty ratio or an input for starting and stopping the operation. The input means (3) includes a manual rotary volume, a manual push volume, an algorithmized automatic variable volume, a switch, and the like. The input means (3) may be omitted when the duty ratio in the dead zone is a constant value. (4) is a depolarization means, which has a function of short-circuiting between the output terminals during a pause period of pulse output. Examples of means for short-circuiting between the output terminals include one in which two switching elements having different channel configurations are connected complementarily, a totem pole type output switching circuit, and the like. Specifically, it is described in Japanese Patent Publication No. 45461. Further, it may share the operation of converting to a pulse provided with current, voltage or power.
(5) is an output end, which is connected to a conductor that controls the contact interface with the surface of the living body skin. The conductor is divided into a conductor and an indifferent conductor, and a drug is contained in one or both of them.
[0007]
Next, the operation will be described with reference to the drawings.
The pulse output means (1) outputs a pulse as shown in FIG. The input means (3) outputs a signal indicating a duty ratio adapted to the dead zone. The duty variable means (2) outputs a pulse (FIG. 2 (2)) with the pulse width (T) adjusted in accordance with this signal.
The pulse shown in FIG. 2 (2) output from the duty variable means (2) is converted into a pulse having a desired current, voltage and power by the depolarization means (4), and is output to the output terminal (5). Incidentally, the pulse output from the depolarizing means (4) is in a state where the frequency and duty ratio are the same as the input pulse and the pulse amplitude is amplified as shown in FIG. 2 (3). In FIG. 1, the pulse output means (1) and the duty variable means (2) are described separately, but can be replaced by a single circuit such as a variable duty type astable multivibrator.
[0008]
Next, the embodiment of FIG. 2 will be described in detail with reference to FIG.
FIG. 3 shows a combination of a microcomputer and depolarization means.
(6) is a microcomputer, which has a built-in program and has a processing capability of 4 bits, 8 bits, etc., and these performances are appropriately selected depending on the complexity and type of dosage form.
(7) is a battery, which consists of a coin-type, button-type primary or secondary battery of 1.5V to 3V, or an ordinary AA, 006P dry battery.
(4) is depolarization means having the same configuration as that of FIG. 1, but a specific example of the circuit is shown here. (41) is a P-channel FET, and (42) is an N-channel FET. The gate of each FET is connected to the output of the microcomputer (6), but an FET drive circuit may be added if necessary. The other components are the same as those shown in FIG.
Next, the operation will be described. It is assumed that the microcomputer (6) stores a program related to the electrical output pattern for medication in advance. A start signal is manually or automatically input from the input means (3). The microcomputer (6) executes the above program and outputs, for example, a pulse with a duty ratio of 75%. This pulse is input to the depolarization output means (4). When the pulse output from the microcomputer (6) is “1”, the FET (41) is turned on, the FET (42) is turned off, and the electric energy of the battery (7) is outputted to the output terminal (5). Furthermore, it is applied to the skin through a conductor. When the pulse output from the microcomputer (6) is “0”, the FET (41) is turned off, the FET (42) is turned on, and the application of electric energy to the battery (7) is stopped. Since (42) is turned off, the output terminals (5) are electrically short-circuited to cause depolarization.
Since the microcomputer (1) can freely set the pulse period, pulse width, pulse interval, and pulse output of the pulse output by the program, there are variations of pulses as shown in FIG. Output can be done.
FIG. 4 (1) shows a case where a depolarizing pulse (FP) having a 75% dead zone duty is continued for a predetermined time and then changed to a depolarizing pulse (NP) having a duty ratio of 30%. The frequency of the 75% depolarization pulse (FP) is, for example, 5 KHz, and the frequency of the 30% depolarization pulse (NP) is, for example, 40 KHz.
In FIG. 4 (2), a depolarization pulse (FP) having a 75% duty is continued for a predetermined time, then a depolarization output (SP) is output for a predetermined time, and a depolarization pulse having a duty of 30% is output for a predetermined time. To do.
FIG. 4 (3) shows a further operation by changing the combination of 75% depolarization pulse (FP), depolarization output (SP), and 30% depolarization pulse (NP) shown in FIG. 4 (2). This is a state where a stopped state (DP) is added.
Note that FIG. 4 is merely an example, and the present invention is not limited to this pattern. The frequency is not limited as long as it is in the range of 1 KHz to 100 KHz. This variation is advantageous when using 75% depolarizing pulses. That is, in the case of 75% depolarization pulse (FP), the depolarization time is only 1/4 of one pulse period. Depolarization is to short the charge accumulated by the pulse output to the peripheral percutaneous on electrical circuit, the electrical path formed when the resistance component is numerous and takes time to short-circuit discharge neutralization In some cases. Accordingly, in the 75% depolarization pulse whose depolarization time is shortened, it may be necessary to additionally form a depolarization pulse or a stable depolarization pulse output state with a long depolarization time.
However, even when the microcomputer outputs only a 75% depolarization pulse, it may be depending on the type of medicine, the patient's condition, and so on.
Note that not only a microcomputer can form a variety of pulse patterns, but depending on the number of pulse patterns, etc., a single IC such as a combination of one-chip multivibrators or a gate array may be sufficient. Applicable. In addition, when the output form of the microcomputer has a complementarity such as C-MOS and the current required for administration is a minimum amount, the depolarization means (7) shown in FIG. The complementary output form itself also serves as an unnecessary circuit, which makes the circuit simpler. Further, as described above, the depolarization circuit can be accommodated in the gate array.
[0009]
The output terminal (5) in FIGS. 1 and 3 is connected to a conductor formed of an indifferent conductor and an inductive conductor that forms an interface with the skin. The conductor is composed of an electrode made of a conductive member, a drug and a drug holding layer, and if necessary, supplies moisture to the drug holding layer to form a stable conductive path. A pressure-sensitive adhesive member layer is added for imparting. The drug is contained or added to either or both of the guide conductor and the indifferent conductor, but in either case, the other conductor does not need to form a drug holding layer, For example, you may replace with the laminated structure of an electroconductive gel and an electrode. Moreover, as a conductive member which comprises an electrode, what has reversibility (non-polarization property) is preferable, for example, silver (Ag) and silver chloride (AgCl) are suitable. Specific examples of the structure of the conductor are shown in Japanese Patent Application No. 174645 and Japanese Patent Application No. 158939.
Next, drug examples used in the present invention are shown below.
Local anesthetics lidocaine hydrochloride antitussive expectorant cromoglycate sodium, ketotifen fumarate bronchodilator formoterol fumarate analgesic agent nalbuphine lactate, pentazocine lactate, diclofenac sodium cardiotonic agent, centaneil, fentanyl tartrate, dopamine psychostimulant perphenazine hydrochloride, Phenothiazine antibiotic cefotetanni sodium, dibekacin sulfate, amikacin sulfate, netilmycin sulfate, sisomycin sulfate antineoplastic agent madriamycin, mitomycin C, bleomycin hydrochloride, lentinan, picibanil, vincristine sulfate, cisplatin circulatory function improver nicamethate citrate, hydrochloric acid Meclofenoxate, Lisuride maleate, Calcium hopantenate ventilator Allopurinol and other peptides LHRH, enkephalin, endorphin, interferon, insulin, calcitonin, TRH, oxytocin, repressin, vasopressin, glucagon, pituitary hormone (HGH, HMG, HCG, desmopressin acetate), follicular luteal hormone, growth hormone secretion factor, etc. .
[0010]
Experimental example Output voltage 6V, 12V, depolarization pulse output device capable of variable duty (9% to 80%) at frequency 5KHz, and laminate of conductive member coated with carbon material on titanium sheet and 10% PVA gel Was used as a conductor (area 22 cm ² ). Wearing this conductor on the human forearm and measuring the skin irritation and peak current (Ip), average current (Im), and effective current (Ie) values when applying electrical output with varying duty ratio . The feeling about the stimulus was set so that the number increased as the stimulus became stronger with 10 as a unit according to the judgment of the subject. 0 for insensitive. The results are shown in Table 1.
[Table 1]

As shown in Table 1 (1), by increasing the duty ratio, the effective current (Ie) increases, and at the same time the subject gradually feels a stimulus, but at a duty ratio of 75% and an effective current of 1.3 (mA). I became insensitive. When the output voltage was set to 12V and the same thing was done, as shown in Table 1, (2), the subject was the same as when the output voltage was 9 (V) with a duty ratio of 75% and an effective current of 1.36 (mA). Never felt irritation and was insensitive. It has been shown that the effective current that directly affects the dosing efficiency is greatly increased in spite of being insensitive.
[0011]
【The invention's effect】
As described above, the present invention can increase the dosing efficiency in a painless state or insensitive state by outputting a depolarizing pulse with a frequency of 1 kHz to 100 kHz and a duty ratio of 55% to 85%. Has an effect.
[Brief description of the drawings]
FIG. 1 is a diagram showing an embodiment of the present invention.
FIG. 3 is a diagram showing an embodiment of the present invention.
FIG. 2 is a diagram for explaining the operation of FIG. 1;
4 is a diagram for explaining the operation of FIG. 3; FIG.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Pulse output means 2 Duty variable means 3 Input means 4 Depolarization pulse production | generation means 5 Output terminal 6 Microcomputer

Claims (2)

After a dead zone depolarizing pulse having a frequency of about 1 KHz to 100 KHz and a duty ratio of 60 to 75% and continuously generating a dead zone depolarizing pulse that forms a depolarized state in the pulse interval of the dead zone pulse is output for a predetermined time. ,
It is formed by outputting a depolarization pulse that forms a depolarized state at a pulse interval of a pulse output of 30% duty and a frequency of 40 KHz between the terminals that output the dead zone depolarization pulse. An iontophoresis device having a pulse output means for outputting a therapeutic pulse and a conductor including a conductive member made of Ag / AgCl that outputs the therapeutic pulse. A non-sensitive area pulse having a frequency of about 1 KHz to 100 KHz and a duty ratio of 75 to 80%, and continuously outputting a non-sensitive area depolarizing pulse that forms a depolarized state in the interval between the non-sensitive area pulses for a predetermined time. ,
It is formed by outputting a depolarization pulse that forms a depolarized state at a pulse interval of a pulse output of 30% duty and a frequency of 40 KHz between the terminals that output the dead zone depolarization pulse. An iontophoresis device comprising a pulse output means for outputting a therapeutic pulse, a conductor including a conductive member made of carbon and titanium for outputting the therapeutic pulse.

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