JPH0767971A - Device for iontophoresis - Google Patents

Abstract

PURPOSE:To remarkably increase the current quantity without giving a pain or an uncomfortable stimulus and apply efficient endermism by providing a depolarizing means performing depolarization between therapeutic pulse output terminals during the rest period of therapeutic pulses formed based on specific insensible band pulses having a specific frequency and a specific duty ratio. CONSTITUTION:A pulse output means 1 outputs pulses, and an input means 3 outputs the signal indicating the duty ratio compatible with the insensible band. A duty-variable means 2 outputs the pulses adjusted to the pulse width according to this signal, and the pulses outputted by the duty-variable means 2 are converted into the pulses having the desired current, voltage, and power by a depolarizing means 4 and outputted to an output terminal 5. The pulse frequency outputted by the pulse output means 1 is set in a range of about 1kHz-100kHz, and the duty ratio is set to a specific insensible band in a range of 55-85%. A sufficient medication effect can be attained in the no-pain state or in the insensible state.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a device for iontophoresis.

[0002]

2. Description of the Related Art Iontophoresis (iontophoresis) has recently been attracting more and more attention as an effective topical administration method for promoting percutaneous absorption of ionic drugs (Glass JM et al., International Journal).
Observatory (GlassJM et al., Int. J. Derm
atol.) 19 519 (1980); Russo Jay. , American Journal of Hospital Pharmacy (Russo J., Am.J. Hosp. Pharm.) 37 8
43 (1980); Gangarasa Elpie et al. ， Journal of Pharmacologic Experiment
And Therapy (Gangarosa LPet al., J. Pharmaco
l. Exp. Ther.) 212 377 (1980); Kwanbies et al. , Journal of Infectious Dishes (Kwon BS et al., J. Infect. Dis.) 14
0 1014 (1979); Hill JM et al. , Annual of New York Academia of Science (Hill JM et al., Ann. NY.Acad. Sci.) 284
604 (1977); Tannebaum Em. , Physical Therapy (Tannebaum M., Phys. Ther.) 607
92 (1980) and Earl H. Guy ed. Advanced Drug Delivery Reviews (RHGuy
Advanced Drug Delivery Reviews) 9 (1992) 11
9-607, etc.). The iontophoresis in these prior arts is usually a function of an output terminal of a continuous normal flow generator or an intermittent normal flow generator and a conductor formed by coating a conductor such as a metal plate with absorbent cotton impregnated with a chemical solution or the like. Since it is made by connecting with a non-insect child, its implementation is quite complicated, and although it is an extremely effective dosing method, its widespread use must be limited. However, recently, it has been disclosed that a transdermal administration without burns can be performed by using a pulse output means having a depolarizing function as an electric output for administration (Japanese Patent Laid-Open No. Sho 60).
No. 156475). However, there are still some parts that have not been clarified in various aspects, such as the relationship between electric output and medication efficiency.

[0003]

In view of the above, the present inventors have earnestly studied and as a result, have found that the frequency is about 1 KHz to 100 KH.
z, a pulse generation means for generating a specific dead zone pulse in a duty ratio range of 55 to 85%, and a treatment pulse output terminal during a rest period of a treatment pulse formed based on the pulse generated by the pulse generation means. Surprisingly, a device for iontophoresis having a depolarizing means for depolarizing the space allows the patient to receive a current amount for energizing the living body without feeling pain, unpleasant stimulation, or the stimulation itself. We have dramatically increased the number and achieved efficient transdermal administration.

The pulse frequency output by the pulse generating means is set in the range of about 1 KHz to 100 KHz. In a range other than this, for example, at about 1 KHz or less, the frequency band is used by the low-frequency therapeutic device, and the frequency band is easily felt by the living body, which is not suitable for medication. On the other hand, if the frequency is 100 KHz or more, the energy consumption of the circuit itself and the increase of loss resistance due to the heat generation of each part become significant, which is not preferable. The duty ratio of the pulse output by the pulse generation means is set to a specific dead zone in the range of 55 to 85%. With this value, the patient himself does not feel any pain or uncomfortable stimulus even though the pulse is close to direct current. At a duty ratio other than this dead zone, as in the case of using a direct current, the user feels a jarring pain or an uncomfortable feeling, and is unable to administer medication. Iontophoresis by direct current is a means that has been studied so far, but it is a low-practical means because it causes burns and pain even at low voltage. On the other hand, however, it is also reported that the drug administration efficiency is good, partly because the effective current amount flowing in the living body is large. The duty ratio indicating the dead zone slightly varies depending on the electrode material forming the conductor. For example, the dead zone when using mainly carbon and titanium as electrodes is 7
In the range of 5 to 80%, the dead zones when Ag / AgCl is used as the electrode exist in the duty ratio of 60 to 75%, respectively. Further, since this dead zone may slightly vary depending on the individual, it is also useful to further provide a duty ratio adjusting means.

The depolarizing means shown in the present invention is disclosed in JP-A-60
No. 156475 discloses a circuit or an output pulse that electrically short-circuits between output terminals connected to a pair of conductors that form an interface with the skin between pulse pauses between pulse intervals. For example, the one provided with a circuit for outputting a pulse of opposite polarity is exemplified.

[0006]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS (1) is a pulse output means, which comprises a self-excited multivibrator, etc., and has a frequency of 1 (K
Output a pulse of (Hz) to 100 (KHz). The pulse output means (1) may have functions such as frequency adjustment. (2) is a duty adjusting means, which is composed of a monostable multivibrator or the like, which 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 additionally provided with an input means (3) for performing an input for adjusting the duty ratio or an input for starting and stopping the operation. Input means
(3) has a manual rotary volume, a manual push volume, or an algorithmized automatic variable volume, a switch, etc. In addition, input means (3)
May be omitted when the duty ratio of the dead zone is a constant value. Reference numeral (4) is a depolarizing means, which has a function of short-circuiting the output terminals or outputting a pulse having a reverse polarity during a pulse output suspension period. Examples of means for short-circuiting between the output terminals include one in which two switching elements having different channel configurations are connected in a complementary manner, a totem pole type output switching circuit, and the like. For more details, Tokuhoku 2
No. 45461, and depolarization due to reverse pulse output are described in Japanese Patent Publication No. 41185/1990. Further, it may share the operation of converting it into a pulse provided with current, voltage or power. (5) is an output terminal, which is connected to a conductor that controls a contact interface with the surface of the living body skin. The worm is divided into a guan and a non-guan, and a drug is contained in either or both of them.

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 varying means (2) outputs a pulse (FIG. 2 (2)) whose pulse width (T) is adjusted according to this signal. Fig. 2 (2) output by the duty changing means (2)
The pulse indicated by is the depolarizing means (4), and the desired current, voltage,
It is converted into a pulse having electric power and output to the output terminal (5). The pulse output from the depolarizing means (4) is as shown in FIG.
As shown in (3), the frequency and duty ratio are the same as those of the input pulse, and the pulse amplitude is in the amplified state.
Further, in FIG. 1, the pulse output means (1) and the duty varying means (2) are described separately, but they can be replaced by one circuit such as a duty varying type unstable multivibrator.

Next, the embodiment of FIG. 2 will be described in detail with reference to FIG. FIG. 3 shows a combination of a microcomputer and depolarizing means. (6) is a microcomputer, which has a built-in program and has a processing capacity of 4 bits, 8 bits, and the like, and these performances are appropriately selected depending on the complexity and type of the medication mode. (7) is a battery, which is a coin-type or button-type primary of 1.5V to 3V,
To a secondary battery or a normal AA, 006P dry battery or the like. (4) is a depolarizing means, which has the same configuration as that of FIG. 1, but an example of a specific circuit is shown here. (41)
Is a P-channel FET, and (42) is an N-channel FET. The gate of each FET is a microcomputer
Although connected to the output of (6), an FET drive circuit may be added if necessary. Since the other components are the same as those in FIG. 1, the same numbers are given and the description thereof is omitted. Next, the operation will be described. It is assumed that the microcomputer (6) stores a program relating to the electrical output pattern for prescription medication. A start signal is manually and automatically input from the input means (3). The microcomputer (6) executes the above program and outputs a pulse having a duty ratio of 75%, for example. 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 output to the output end (5), Further, it is applied to the skin via the conductor. When the pulse output from the microcomputer (6) is "0", F
At the same time when the ET (41) is turned off, the FET (42) is turned on, and the application of the electric energy of the battery (7) is stopped,
Since (42) is turned off, the output terminals (5) are electrically short-circuited and depolarization is performed. Microcomputer
In (1), it is possible to freely set the pulse period, pulse width, pulse interval, and start / stop of pulse output by the program, so pulse output with variations as shown in FIG. It can be carried out. In FIG. 4 (1), a depolarizing pulse (FP) having a duty of 75% dead zone is continuously applied 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
The frequency of the KHz, 30% depolarization pulse (NP) is, for example, 40 KHz. In FIG. 4 (2), a depolarizing pulse (FP) having a duty of 75% is continued for a predetermined time, and then a depolarizing output (SP) is output for a predetermined time, and a depolarizing pulse having a duty of 30% is output for a predetermined time. To do. Figure 4 (3)
Shows a state in which the operation is further stopped by changing the combination of the 75% depolarization pulse (FP), the depolarization output (SP), and the 30% depolarization pulse (NP) shown in FIG. 4 (2) ( DP) is added. Note that FIG. 4 is merely an example, and the pattern is not limited to this. The frequency is not limited as long as it is in the range of 1 KHz to 100 KHz. This variation is convenient when using a 75% depolarization pulse. That is, in the case of the 75% depolarization pulse (FP), the depolarization time is only 1/4 of one pulse period. Depolarization short-circuits the electric charge accumulated by the pulse output around the transcutaneous area on an electric circuit. Alternatively, a reverse pulse is applied to substantially neutralize, but the electrical path formed at that time has many resistance components,
It may take time to neutralize the short-circuit discharge. Therefore, in the case of the 75% depolarization pulse in which the depolarization time is shortened, it may be necessary to additionally form a stable depolarization pulse output state in the depolarization state or in the state where the depolarization time is long. However, even when the microcomputer outputs only the 75% depolarization pulse, it may be dependent on the type of drug, the condition of the patient, and the like. It should be noted that not only a microcomputer is capable of forming various pulse patterns, but depending on the number of pulse patterns and the like, combinations of one-chip multivibrator and gate array etc.
Even individual ICs can be sufficiently applied.
Further, when the output form of the microcomputer has complementarity such as C-MOS and the current required for the administration is a very small amount, the depolarizing means (7) shown in FIG. Since the complementary output forms themselves are combined, the circuit becomes simpler because it is not necessary. Further, as described above, the gate array can also accommodate the depolarization circuit.

The output end (5) of FIGS. 1 and 3 is connected to a conductor consisting of an indifferent conductor and an indirect conductor forming an interface with the skin. The conductor is composed of an electrode made of a conductive member, a drug and a drug-retaining layer, and if necessary, supplies water to the drug-retaining layer to form a stable conductive path. An adhesive member layer is added to have the above. The drug is contained or added to either or both of the gate conductor and the non-barrel conductor, but in the case of either one, the other conductor does not need to form a drug holding layer, For example, it may be replaced with a laminated structure of a conductive gel and electrodes. The conductive member forming the electrode is preferably a reversible (non-polarizable) material such as silver (A
g) and silver chloride (AgCl) are preferred. Specific examples of the structure of the Michiko are shown in Japanese Patent Application No. 174645/1993 and Japanese Patent Application No. 158939/1992. Next, examples of drugs used in the present invention are shown below. Local anesthetic Lidocaine hydrochloride Antitussive expectorant Sodium cromoglycate, Ketotifen fumarate Bronchodilator Formoterol fumarate Analgesic Nalbuphine hydrochloride, Pentazocine lactate, Diclofenac sodium cardiotonic agent, Sentenyl, Fentanyl tartrate, Dopamine feline nervine hydrochloride Phenothiazine Antibiotic cefotetani sodium, dibekacin sulfate, amikacin sulfate, netilmycin sulfate, sisomycin sulfate Anti-neoplastic agent Madriamycin, mitomycin C, bleomycin hydrochloride, lentinan, picibanil, vincristine sulfate, cisplatin circulatory function improver nicotinate citrate, hydrochloride Meclofenoxate, lisuride maleate, calcium fopantenate Gout remedy allopurinol Other peptides LHRH, enkephalin, endorphin, interferon, insulin, calcitonin, TRH, oxytocin, lipresin, vasopressin, glucagon, pituitary hormone (HGH, HMG, HCG, desmopressin acetate), luteinizing hormone, growth hormone secretory factor, etc. And so on.

Experimental Example A depolarizing pulse output device capable of varying the duty (9% to 80%) at an output voltage of 6 V and 12 V and a frequency of 5 KHz, and a conductive member in which a titanium sheet material is coated with a carbon material 1
A laminate with 0% PVA gel was used as a conductor (area 22 cm ² ). This conductor is attached to the forearm of a human body, and the feeling and the peak current (Ip), the average current (Im) of the skin stimulation when the electric output with the changed duty ratio is applied,
The effective current (Ie) value was measured. The feel of the stimulus was set such that, when the stimulus was stronger, the number was larger, with 10 being one unit, according to the judgment of the subject. In the case of no feeling, it is 0. The results are shown in Table 1.

[Table 1] As shown in Table 1 (1), by increasing the duty ratio, the effective current (Ie) rises and at the same time, the subject gradually feels stronger stimulus, but with the duty ratio of 75% and the effective current of 1.3 (mA). I became blind. When the output voltage was set to 12 V and the same operation was performed, as shown in (2) of Table 1, the duty ratio was 75% and the effective current was 1.36 (m
As in the case of the output voltage of 9 (V) in A), the test subject did not feel any stimulus, and was also insensitive. It has been shown that the effective current, which directly affects the medication efficiency in spite of such a dead state, is greatly increased.

[0011]

As described above, the present invention has a frequency of 1 KHz.
By outputting a depolarizing pulse having a duty ratio of ˜100 KHz and a duty ratio of 55% to 85%, there is an effect such that sufficient medication efficiency can be achieved in a painless state or in a dead state.

[Brief description of drawings]

[Figure 1]

FIG. 3 is a diagram showing an embodiment of the present invention.

FIG. 2 is a diagram for explaining the operation of FIG.

FIG. 4 is a diagram for explaining the operation of FIG.

[Explanation of symbols]

 1 pulse output means 2 duty variable means 3 input means 4 depolarization pulse generation means 5 output terminal 6 microcomputer

Claims (1)

[Claims] 1. A pulse generating means for generating a pulse in a dead zone at a frequency of about 1 KHz to 100 KHz and a duty ratio of 55 to 85%, and a treatment pulse formed on the basis of the pulse generated by the pulse generating means. A device for iontophoresis, comprising depolarizing means for depolarizing between treatment pulse output terminals during the rest period.