JPH06327777A - Electrical chemical introducing device - Google Patents

Abstract

PURPOSE:To increase the amt. of chemical to be introduced per unit time and to suppress dermatopathy by providing the electrical chemical introducing device for impressing a voltage on electrode pair surfaces, one of which contains the chemicals, and making the chemical penetrate with plural electrode pairs. CONSTITUTION:This electrical chemical introducing device is provided with, for example, two sets of the electrode pairs. Exploring electrodes 3, 5 are electrodes contg. the chemical and indifferent electrodes 4, 6 are electrodes which do not contain the chemical. The voltage supplied by a DC power source 1 is impressed between the electrode pairs 3 and 4 to introduce the chemical from the exploring electrode 3 into an organism 9. The impression of the voltage is changed over to between the electrode pairs 5 and 6 by a timer switch 2 to stop the chemical introduction from the exploring electrode 3 and to introduce the chemical into the organism 9 from the exploring electrode 5 before polarization begins to be generated between electrode the pairs 3 and 4. The impression of the voltage is changed over to between the electrode pairs 3 and 4 by the timer switch 2 to stop the introduction of the chemical from the exploring electrode 5 and to introduce the chemical again from the exploring electrode 3 to the organism 9 before the polarization begins between the electrode pairs 5 and 6. The polarization state is averted by repeating the operation described above and the chemical are continuously introduced.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an electric drug introduction device. More specifically, the present invention relates to an electric drug introduction device, which is one means of a drug delivery system, which enables highly efficient drug introduction while suppressing skin disorders.

[0002]

2. Description of the Related Art In recent years, an electric drug introduction device has attracted attention as a non-invasive drug administration method, and various studies have been made. However, this method has a problem that when a direct current voltage is applied to the skin, a polarized state occurs due to the capacitive component of the skin, and a current for introducing the drug hardly flows. Therefore, as a method for solving this problem, an apparatus having a depolarizing function has been proposed. For example, Japanese Unexamined Patent Publication No. 60-156475 discloses a method of performing depolarization by providing a switch mechanism that short-circuits both electrodes or a mechanism that applies a pulse of opposite polarity between both electrodes during a drug introduction suspension period. . Further, Japanese Patent Laid-Open No. 64-11565 discloses a constant voltage device with a voltage of 5 to 20V.
Is applied for 1 to 60 seconds to reduce the electric resistance of the skin, and then a voltage of 0 to 5 V is applied to increase the absorption rate of the drug. Further, JP-A-3-4527
Japanese Unexamined Patent Publication No. 2 (1994) discloses a method of applying an AC voltage having a predetermined frequency between electrodes to prevent polarization from occurring.

[0003]

However, in spite of the above improvements, in the conventional drug introduction device, the depolarization operation is performed at the time when the drug introduction is stopped. Therefore, the drug is introduced into the living body during the depolarization operation. The current situation is that none of this has been done.
For this reason, the amount of the drug introduced per unit time is limited, and it is not suitable for administration of the drug for the treatment that requires rapid-acting. Further, it has been pointed out that when a high voltage is used, even a high frequency pulse causes skin damage.

Therefore, the present invention solves the above-mentioned drawbacks of the prior art, provides a new electric drug introduction device capable of increasing the amount of drug introduced per unit time and suppressing skin disorders. The purpose is to do.

[0005]

That is, the present invention is
In order to solve the above-mentioned problems, at least one is an electric drug introduction device for applying a voltage between electrode pairs containing a drug to permeate the drug, wherein the device has a plurality of such electrode pairs. A drug introduction device is provided. Further, one aspect of the present invention is to include a timer switch mechanism for sequentially switching and applying a voltage to each of the plurality of electrode pairs.

[0006]

The medicine introducing device of the present invention will be described in detail with reference to the drawings. FIG. 1 is a block diagram of the entire configuration showing an example of the device of the present invention in the case of including two pairs of electrodes. In FIG. 1, the gates (3) and (5) are electrodes containing a drug, and the gates (4) and (6) are electrodes containing no drug. The voltage supplied by the DC power supply (1) is applied between the electrode pairs (3)-(4), and the drug is introduced into the living body (9) from the guide (3). Then, in the case of the device example of the configuration of FIG. 1, before the polarization starts to occur between the electrode pairs (3)-(4), the voltage is applied by the timer switch (2) between the electrode pairs (5)-(. 6), the drug introduction from the guider (3) is stopped, and the drug is introduced from the guider (5) into the living body (9). Next, between the electrode pair (5)-
Before polarization begins to occur in (6), the voltage application is switched between the electrode pairs (3)-(4) by the timer switch (2), the drug introduction from the gate conductor (5) is stopped, and the gate conductor is turned on again. The drug is introduced into the living body (9) from (3). Thereafter, in the same manner, voltage is applied between the electrode pairs at the desired voltage switching interval (3).
-By alternately switching to (4), (5)-(6),
The drug is continuously introduced while avoiding the polarized state.

Further, when the number of electrode pairs is more than two, it is possible to sequentially introduce the drug from a plurality of locations by sequentially switching the voltage application between the electrode pairs. Of course, the electrode pair used in this invention is
Any material can be used as long as it has a portion for applying a voltage and at least one of which has a reservoir portion capable of containing an aqueous solution of a therapeutic agent.

The voltage used at that time may be any of DC voltage, pulse DC voltage and AC voltage as long as it is not a high voltage that causes skin damage. The frequencies of the pulse DC voltage and the AC voltage are not particularly limited, but are preferably in the range of 1 Hz to 200 kHz. The current intensity between the electrodes is also not particularly limited, but is preferably 0.01 to 20 mA, more preferably 0.1.
Is in the range of 5 mA. The switching interval of voltage application is not particularly limited because it varies depending on the drug and the energization condition, but is preferably in the range of 0 to 60 minutes.

The conditions such as the type of voltage, the frequency, the current intensity, and the switching interval of voltage application as described above can be the same or different for all electrode pairs. Further, the order of applying the voltage to each electrode pair may be any order. Further, when the timer switch is used, any timer can be used as long as it has a timer having a variable voltage application switching interval and the circuit can be switched by the timer.

FIG. 2 is an example of an external view of an electric drug introduction device produced based on the block diagram of the entire structure shown in FIG. In FIG. 2, the gates (3) and (5) are electrodes containing a drug, and the gates (4) and (6) are electrodes containing no drug. If the desired current value is set in advance with the current value setting knob (10), the power switch (1
After turning on 1), the voltage set by the DC power supply (1) built into this device is applied between the electrode pairs (3)-(4), and the drug is introduced into the living body from the guide (3). To be done. In addition, if the application switching timer (12) is set in advance for the time when the polarization starts to occur between the electrode pairs, the device shown in FIG. 1 installed in the device before the polarization starts between the electrode pairs (3)-(4). The timer switch (2) switches the voltage application between the electrode pair (5)-(6), stops the drug introduction from the guide element (3), and causes the drug to enter the living body (9) from the guide element (5). be introduced. Next, before the polarization starts to occur between the electrode pair (5)-(6), the timer switch (2) applies the voltage at the time set by the application switching timer (12) between the electrode pair (3)-. Switching to (4), the drug introduction from the guide (5) is stopped, and the drug is introduced into the living body (9) from the guide (3) again. Thereafter, similarly, by alternately switching the voltage application between the electrode pairs (3)-(4) and (5)-(6) at desired voltage switching intervals, the polarization state is avoided and the drug is continuously introduced. To do.

An energization display lamp (13) indicates between the electrode pairs to which a voltage is applied, and between the electrode pairs (3)-(4),
Turn on the current indicator lamps (13) of (5)-(6) respectively.
In the case of H1 and CH2, when voltage is applied between the electrode pairs (3)-(4), CH1 lights up, and (5)-
When voltage is applied to (6), CH2 lights up.
FIG. 3 shows an example of introducing a drug from the lower abdomen using an apparatus having two electrode pairs as an example of introducing a drug using the device of the present invention.

The electric drug introducing device (14) is fixed to the lumbar region using the fixing belt (15), and the drug-containing guides (3) and (5) and the drug-free non-conductor ( 4),
(6) is attached to the lower abdomen. The desired current value is set by the current value setting knob (10) installed in the electric drug introduction device (14) and the voltage application switching time to the two electrode pairs is set to the application switching timer (12). ),
When the power switch (11) is turned on, a voltage is applied between the electrode pair (3)-(4), and the drug is introduced into the lower abdomen from (3).

When the time set in the application switching timer (12) of FIG. 2 elapses, the timer switch (2) of FIG.
The voltage is applied between the electrode pairs from (3)-(4) to (5).
-Switching to (6), the drug is introduced into the lower abdomen from (5). After that, the voltage is similarly applied between the electrode pairs (3)-
Since it is switched to (4) and (5)-(6), the drug is continuously introduced from the lower abdomen.

The drug used in the present invention is not limited in kind, and any suitable drug can be used. For example,
Anticancer agents such as cisplatin, mitomycin C and adriamycin are preferably used for cancer treatment. For regulating blood pressure, antihypertensive agents such as reserpine, guanethidine sulfate, chlorothiazide and hydrochlorothiazide, and pressor agents such as norepinephrine are preferably used.

For the treatment of arrhythmia, heart disease, cardiac function, and regulation of pulse wave, cardiotonic agents such as dichitoxin ouabain, arrhythmic therapeutic agents such as quinidine sulfate, procainamide hydrochloride, propranolol and the like are preferably used. Body temperature regulation, fever reduction,
For analgesia, antipyretic analgesics such as sodium salicylate, aspirin and acetaminophenone are preferably used.

To control the water content in the body and promote diuresis, diuretics such as azosemide, furosemide, acetoazolamide and solductone are preferably used. For the treatment of urinary incontinence, agents capable of controlling contraction or relaxation of bladder muscle or urethral sphincter such as terodiline hydrochloride, oxybutynin hydrochloride, flavoxate hydrochloride and ubretide are preferably used.

For the treatment of diabetes, peptide drugs such as insulin are preferably used. One or more of these drugs may be dissolved or dispersed in water or an aqueous solution adjusted to a desired pH and then charged into a drug reservoir in the electrode. At this time, different types of chemicals may be contained in the respective electrodes, or the same may be contained therein. The drug concentration at that time can be arbitrary. For example, it can be used as a dispersion by increasing the solubility or higher,
It is desirable to adjust appropriately according to the required skin permeation rate.

The site to which the electrode of the present invention is applied is not particularly limited, but the upper limb, lower limb, abdomen, waist and the like are preferable. In addition, a conductor that is an electrode containing a drug,
The distance to the indifferent conductor, which is an electrode containing no drug, is not particularly limited, but a distance of 0.5 to 10 cm is preferable.

The present invention will be described in more detail below with reference to examples.

[0020]

Example 1 Insulin was dissolved in distilled water at a concentration of 10 mg / ml,
1.5 ml thereof was loaded into each of the electrodes (3) and (5) of the electric drug delivery device equipped with the two pairs of electrodes shown in FIG. 1, and they were shaved. Male,
200 g) was attached to the back together with the electrodes (4) and (6). The positive electrode is connected to the electrodes (3) and (5), the negative electrode is connected to the electrodes (4) and (6), and the direct current power source (1) such as a dry battery is used.
5 mA current for a total of 120 minutes between electrode pairs (3)-
Power was supplied while switching to (4) and (5)-(6) alternately. Switching of voltage application to each electrode pair was performed using a timer switch (2), and switching was performed at intervals of 0.05 seconds.

As a result, the blood glucose level was significantly lowered, and no significant skin damage was observed at the electrode-attached site despite the use of high current. FIG. 4A is a waveform diagram of the voltage supplied by the DC power supply at that time, and FIGS. 4B and 4C show between the electrodes (3)-(4), (5)-(6). )
It is a waveform diagram of the voltage supplied to. Example 2 Example 1 was repeated except that one set of electrode pairs was further added to the apparatus of Example 1 and the electrical drug introduction apparatus of FIG. 5 provided with a total of three sets of electrode pairs was used and the energization time was 30 minutes. The drug was introduced according to

As a result, the blood glucose level of the hyperglycemic hairless rats was significantly lowered despite shortening the energization time. No skin damage was observed at the electrode attachment site. Figure 6
FIG. 6A is a waveform diagram of the voltage supplied by the DC power supply at this time, and FIGS. 6B, 6C, and 6D show interelectrode electrodes (3)-(4), 5)-(6), (7)-(8)
It is a waveform diagram of the voltage supplied to. Example 3 , Comparative Example 1 In accordance with Example 2, oxybutynin hydrochloride was charged into electrodes (3), (5) and (7), respectively, and they were shaved on the back of hairless rats (male, 225 g). Electrode (4),
It was attached together with (6) and (8). Electrode (3),
(5) and (7) are connected to the positive electrode and electrodes (4), (6) and (8) are connected to the negative electrode, and a current of 2 mA is applied for a total of 60 minutes between the electrode pairs (3)-(4), ( Power was supplied while alternately switching to 5)-(6) and (7)-(8). The voltage application switching interval for each electrode pair was set to 10 minutes.

As a comparative example, a hairless rat (male, 225 g) was shaved by charging oxybutynin hydrochloride into the electrode (3) using the electric drug introduction device of FIG. 7 equipped with a pair of electrodes. It was attached together with the electrode (4) on the back of the. Connect the positive pole to the electrode (3) and the negative pole to the electrode (4), and
A current of mA was applied for 60 minutes. FIG. 8 is a waveform diagram of the voltage supplied from the DC power supply to the electric drug introduction device of FIG. 7.

In each case, after administration, blood was collected over time, serum was obtained by centrifugation (2000 rpm, 10 minutes), and then the drug concentration in the serum was quantified by gas chromatography. The results are shown in Table 1. As is clear from Table 1, a significant increase in blood concentration was observed with the device of the present invention.

[0025]

[Table 1]

[0026]

EFFECT OF THE INVENTION With the electric drug introducing device of the present invention,
By sequentially applying a voltage between two or more pairs of electrodes, the drug can be introduced while avoiding the polarized state, and the amount of the drug introduced per unit time significantly increases. In addition, since the drug is introduced from multiple locations, the required amount of drug can be introduced even at low current, and when a high current is applied, the required amount of drug can be introduced in a short time, and the skin The obstacles can be reduced.

In addition, it is possible to administer a drug that requires rapid-acting, which has been thought to be difficult in the past, and to eliminate discomfort due to injection, and to administer a drug to a patient who cannot be orally administered. Is also effective.

[Brief description of drawings]

FIG. 1 is a block diagram of the entire configuration of an electric drug introduction device used in Example 1 of the present invention.

FIG. 2 is an external perspective view illustrating an electric drug introduction device used in Example 1 of the present invention.

FIG. 3 is a schematic view exemplifying a case where the electric drug introduction device of the present invention is attached to a human.

4 (a), (b) and (c) are waveform diagrams of the voltage supplied between the electrodes from the DC power supply according to the first embodiment of the present invention.

FIG. 5 is a block diagram of the entire configuration of the electrical medicine introducing device used in Embodiment 2 of the present invention.

6 (a), (b), (c), and (d) are waveform diagrams of a voltage supplied between electrodes from a DC power supply in Embodiment 2 of the present invention.

FIG. 7 is an overall configuration block diagram of an electrical medicine introducing device used in Comparative Example 1.

FIG. 8 is a waveform diagram of a voltage supplied between electrodes from a DC power supply in Comparative Example 1.

[Explanation of symbols]

 1 DC power supply 2 Timer switch 3 Guan Guo 4 Non-gu Guo 5 Gu Gu Guo 6 Guan Gu Guo 7 Gu Gu Guo 8 Gu Gu Guo 9 Living body 10 Current value setting knob 11 Power switch 12 Application switching timer 13 Energization Indicator lamp 14 Electrical drug introduction device

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Izumi Sakamoto 23, Uji Kozakura, Uji City, Kyoto Prefecture Unitika Ltd. Central Research Laboratory

Claims (2)

[Claims] 1. An electric drug introducing device, wherein at least one of the electrode pairs contains a drug and a voltage is applied between the electrode pair to penetrate the drug. The electric drug introducing device comprises a plurality of electrode pairs. . 2. The electrical medicine introducing device according to claim 1, further comprising a timer switch mechanism for sequentially switching and applying a voltage to each of the plurality of electrode pairs.