JPS59118167A - Conductor for iontophrese and plaster structure - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a conductor for iontophoresis and a plaster device therefor, and particularly to a conductor or plaster structure for iontophoresis which is extremely easy to operate and lightweight and can be directly attached to human skin.

Iontophoresis has recently received increasing attention as an effective topical administration method to promote transdermal absorption of ionic drugs (Glass JM et al.

Int, J. Dermatol, 19519 (
1980); Ru5so J,.

Am, J, Ho5p, Pharm, 37843
(1980); Gangarosal, P et a.
l,, J, Pharmacol, Exp, The
r, 212377 (1980); Kwon BS
et al., J. Infect, Dis, 14
01014 (1979); Hill JM et
al., Ann, NY, Acad.

Sci, 284604 (1977) and Tanne
Baum M, Phys.

Ther, 60792 (1980), etc.).

The iontophoresis in these prior art is usually
An output terminal of a continuous flow generator or an intermittent flow generator;
It is quite complicated to implement because it is made by connecting a conductor such as a metal plate made of a conductor such as a metal plate with absorbent cotton impregnated with a chemical solution, and a similar structure, so it is quite complicated to implement, but it is extremely effective as a medication method. Despite its popularity, its spread was inevitably limited. In addition, since these conductors are generally fixed to the treatment area with a rubber band or the like to apply transdermal electricity, burns are likely to occur due to poor contact between skin debris and the conductor, and constant care must be taken during the treatment. Since it required monitoring with an ammeter, there was no hope that it would become popular as a general home treatment, even if it was only used by doctors.

Therefore, the main object of the present invention is to provide a novel iontophoresis guide or plaster structure that overcomes the difficulties of these known techniques and is extremely easy to operate and lightweight and can be used by directly attaching it to the human skin. be.

First, regarding the conductor structure of the present invention, 1 shown in attached Figures 1 and 2.
A detailed explanation will be given based on examples.

In the figure, the conductor (2) is made of paper material such as water-absorbing paper, cloth material such as gauze,
A water-absorbing member (4) for retaining impregnated with an ionic chemical or electrolyte solution made of a fibrous material such as absorbent cotton, a sponge or porous material such as a synthetic resin open foam or a water-absorbing resin, a metal foil such as aluminum foil, and a conductive material. A current dispersion conductive member layer (5) made of a rubber or resin film or a resin film deposited with a conductive material, and a hydrophilic adhesive layer (5) having skin adhesive properties formed around the water absorbing member (4). ” to gel layer 0
It consists of υ and a backing layer 0@ such as a synthetic resin film laminated integrally thereon.

In this case, the conductive gel layer (5) may be a backing layer formed by vapor-depositing a metal such as aluminum, and appropriate terminals may be provided as required.

Furthermore, the hydrophilic gel layer (4) and the water absorbent member (4)
A barrier layer made of a synthetic resin material or the like may be provided between the gel and the gel to prevent penetration of a chemical solution or the like into the gel.

The conductor of the present invention having the above structure has a water-absorbing member (4).
The member is impregnated with an ionic chemical solution or the like, or the member pre-impregnated with a drug solution is placed and inserted in a predetermined position, and is directly adhered to the skin for use. Therefore, during use, the drug solution holding part is surrounded by an adhesive and hydrophilic gel layer (4), so the moderate water absorption of the gel layer effectively prevents the drug solution from escaping and leaking onto the skin. In addition, the skin adhesion ability of the entire conductor is not weakened, allowing stable electricity supply and accurate local administration of the drug solution.

In other words, according to the conductor of the present invention, an ideal chemical solution or electrolyte solution storage structure that does not require complicated fixing means such as a band and effectively prevents the outflow of the chemical solution, etc. can be achieved at the same time. Since the conductor of the present invention has the above-mentioned effect, it can be widely used by connecting its terminal to various iontophoresis devices. It can be said that the plaster structure for iontophoresis according to the present invention is particularly useful.

Note that FIG. 1 is a plan view of the conductor of the present invention, and FIG. 2 is a sectional view thereof.

Hereinafter, a first embodiment of the plaster structure of the present invention will be described in detail with reference to FIGS. 3 to 5 south of the drawings. In the figure (Old style plaster structure for iontophoresis, it has a seki conductor (2) and a non-seki conductor (3). Cloth material such as gauze, fiber material such as absorbent cotton 7 A water-absorbing member (4) for retaining ionic drug solution immersion consisting of a synthetic resin open foam or a sponge or porous phase of water-absorbing resin, etc., and a hydrophilic gel. 01) and one layer (5) of a conductive part for current dispersion formed of metal foil such as aluminum foil, conductive rubber or resin film, etc. ) is a skin-adhesive conductive gel layer (6) formed in the form of a flexible sheet or film, and a current dispersion conductive member layer (7) formed of aluminum foil or the like as described above, which are laminated and integrated. It was originally formed. A lightweight battery is installed on the top surface of the Seki Doko (2).
For example, a so-called button-shaped battery (8) is installed such that one of its poles, for example, the (-) pole, contacts the current dispersion conductive material layer (5). Further, the (+) pole of this button-shaped battery (8) is connected to a lead wire (9) made of aluminum foil, for example, whose lower surface except near both ends is coated with an insulating coating, to conduct the current dispersion of the indifferent conductor (3). Sex member layer +71
K is connected. (11 is an insulating backing layer. This insulating backing layer 01 is made of, for example, a non-conductive synthetic resin in the form of a flexible sheet or film. 3) are arranged and fixed to this insulating backing layer Ql at a distance, that is, a seki conductor (2), a seki conductor (3) and a button-shaped battery (8).
) are integrally supported and connected by the insulating backing layer QIK.

Further, in this example, an insulating synthetic resin barrier layer H is provided.

Next, the operation and usage of the plaster structure for iontophoresis of the present invention having the structure I will be explained. 1. The water-absorbing material layer (4) of the Kando inductor (2) is impregnated with a desired ionic chemical solution, and then the Kando inductor (2) is attached to a desired position on the human body so as to come into contact with it.

At the same time, the Kan inductor (2) and the inkan inductor (3) form a closed circuit, and the ionic drug in the water-absorbing material layer (4) for impregnating the ionic drug in the Kan inductor (2) is formed. Expense penetration will be accelerated.

The details of each component of the plaster structure of this example are as follows.

Skin-adhesive hydrophilic (conductive) gel layer This layer is preferably made of natural resin polysaccharides such as karaya gum, tragacanth gum, xanthan gum or partially saponified polyvinyl alcohol, polyvinyl formal, polyvinyl methyl ether and their copolymers polyvinylpyrrolidone. , vinyl resins such as polyvinyl methacrylate, polyacrylic acid and its sodium salts, polyacrylamide and its partially hydrolyzed products, partially saponified polyacrylic esters, acrylic resins such as poly(acrylic acid-acrylamide), and other hydrophilic resins. Various natural or synthetic resins having the following properties are softened and plasticized with water and/or alcohols such as ethylene glycol and glycerin to provide a flexible film or sheet gel having self-shape retention and skin adhesion.

On the other hand, when these are conductive gel layers of uncontained conductors, electrolytes such as sodium chloride, sodium carbonate, potassium citrate, etc. are required in the required amount (usually about 1 to 15%) to impart sufficient conductivity to the conductive gel layer. Be added. The hydrophilic (conductive) gel layer suitable for the present invention obtained in this way is in the form of a flexible film or sheet and can closely adhere to the skin, so it has low skin contact resistance and is free of drug ions. The key is that it is not only effective for percutaneous penetration, but also has the advantage of being able to adhere and support the entire structure to the skin without requiring other skin adhesive means such as adhesive tape. In particular, when a natural resin polysaccharide such as the above-mentioned karaya gum is used as a base material for the gel layer, the pI (buffering property to skin protection property, extremely high water retention capacity, moderate skin adhesiveness, etc.) due to the natural polymer acid structure, etc. This not only provides a gel with good electrochemical conductivity, but also provides suitable skin compatibility.

Some preferred composition ranges (parts by weight) of karaya gum gel are shown in Tables 1 and 2 below.

Table 1 Karaya gum 41.4 20-70 Glycerin 54.0 80-30 Water (*
4.6 3 to 40*) When using this as a conductive gel layer for indifferent conductors, use the same amount of saturated saline instead of water.

Table 2 Karaya gum 22 5-4゜Poly(acrylic acid-acrylamide-P) 12 5-50゜Glycerin 60 50-7゜Water
0 5~3゜EVA
Emulsion type adhesive 6 5-15*
) Hercules Co., Ltd. "Reten ■ 521PX" If the conductor of the present invention is made of a hydrophilic polymer material such as those exemplified above, it will absorb a small amount of drug solution at the boundary when it is applied to the skin, but its adhesiveness will be further strengthened by this. Therefore, it constitutes a medicinal liquid part that seals and holds the medicinal liquid on the skin, and it can be said to be extremely simple to use in that it does not particularly require fixing means such as a band.

In addition, when formulating the composition of these gel layers, it is natural that consideration should be given to TE gas chemistry in the same manner as in the case of so-called electrophoretic gels, but the Type of drug and required dose (dosage), duration of use of the patch,
The test is carried out as appropriate so that the amount of conductive dust reaches the required value depending on the output of the battery used, the skin contact area, etc.

Here, other suitable hydrophilicity (conductivity) in this example
More specifically, some of the gel layers are as follows: 1. By a conventional method, the average molecular weight is 440,000, and the degree of saponification is about 60'.
% of polyvinyl alcohol powder was prepared, and 40% of distilled water containing 10% NaCl preheated to 80°C was added to this.
Then, the resulting mixture was heated to 80°C and heated and pressed at a pressure of 0.6 Kq/d for about 20 minutes using a hot press machine to form a flexible sheet with a thickness of 3 mm. I got something. This flexible sheet-like material has sufficient skin adhesion and has a specific resistance of 0.8.
It was KΩ・Vice.

2. A flexible sheet-like conductive gel layer was manufactured using the following composition in the same manner as in 1 above.

(Composition example A) Polyvinylpyrrolidone (PVP-90 manufactured by GAF; average molecular weight 360,000)
...2Or101NaC1-containing distilled water...
・・・・・・・・・402 Glycerin・・・・・・・・・
・・・・・・・・・・・・・・・・・・・・・・・・
40? The obtained sheet had strong skin adhesion and its specific resistance was 0.2 KΩ·F.

(Composition example B) Polyvinyl formal (average molecular weight 1.6 million.

Degree of formalization: 15%; Degree of formalization of raw material polyvinyl alcohol: 60%)・・・・・・・・・・・・・・・152
Distilled water containing 5% NaCl・・・・・・・・・・・・・・・・
・70? Propylene glycol ··········
...151 The obtained sheet has excellent skin adhesion and its specific resistance is 1. It was OKΩ・m.

(Composition Example C) Polyvinyl acetoacetal (average molecular weight 440,000, degree of acetalization 30%; degree of saponification of starting polyvinyl alcohol 70%) 40P 15% Na
C1-containing distilled water ・・・・・・・・・・・・・・・50
7 Ethylene glycol ・・・・・・・・・・・・・・・
......It has skin adhesiveness equivalent to 10 grams of light, and has a specific resistance of 0.75 Ω・α.

3. Sodium polyacrylate (Aronbis SS manufactured by Nihon Tsumugi Co., Ltd.; average molecular weight 3 million to 5 million) 207 with 5% Na
The mixture was uniformly mixed with 1.2 y of C1-containing distilled water and 68 g of glycerin solution, and heated and pressed at 80° C. for 10 minutes to obtain a flexible sheet. This sheet had appropriate skin adhesion and its specific resistance was 0.5 KQ after being left for one day and night.

4. Karaya gum 302 and distilled water 30 containing 5% NaCl
1 and 40 g of glycerin were mixed and heated and pressed to prepare a sheet in the same manner. Specific resistance 0, 6 5 KΩ fist m.

5. Sodium polyacrylate (Aronbis S manufactured by Nippon Junkei Co., Ltd.; average molecular weight 3 million to 5 million) 207 with 7% NaC
1-containing purified water 807, and heated and pressurized to prepare a sheet in the same manner. Specific resistance: 0.47 to 90cm0 As is clear from the above, the composition or range of the gel base material of the hydrophilic (conductive) gel layer of the present invention is not limited to a specific one, and a wide range of hydrophilic polymers can be used. It can be used after being softened and plasticized with alcohol and/or alcohol.
Usually, in order to have shape retention, the hydrophilic polymer has a molecular weight of 10 to 70%.
Selection is made within the composition range of Shigetakano and the remainder water and/or alcohol. Each of the above-mentioned conductive gel layers has a certain level of skin adhesion by itself, but if desired, it may be applied with a sensitive adhesive such as an acrylic adhesive or a vinegar-based adhesive. A pressure adhesive component may also be added.

The above example was explained with reference to the conductive gel layer of the Inkan doshi, but when these are used as the Kando's hydrophilic gel layer or the adhesive layer in the integrated plaster described later, the addition of electrolyte components is only necessary. Of course, that's fine.

Although any ionic drug can be used as long as it is an ion release drug, there are some that have already been widely used in the field of iontophoresis.
Examples of the parts are as follows: iodopotassium, prohydroline hydrochloride, melicol, vitamin B1=B2. pfi
, C and various skin vitamins and skin nutrients such as various amino acids, histamine.

Sodium zalycylate, dexamethacin, epinephrine, hydrocortisone, idoctulidine, insulin, undecylenate, various antibiotics, etc.

Any type of battery can be used as long as it is lightweight and can be attached to the skin, such as lightweight batteries, output button-shaped batteries, sheet-shaped batteries, etc., but the above two types are usually preferred due to their small size and flexibility. .

On the other hand, the current value required to perform iontophoresis is usually on the order of several μA to several 100 μA/i, and the contact resistance between the conductor and the skin is on the order of several ohms to several 10K ohms, so the battery output Although it depends on the contact area between the skin and the conductor, it is approximately 0°5 to 18V. Therefore, if necessary, an amplification element may be used in which several of these lightweight batteries are disposed or stacked or formed into a chip.

Further, if necessary, a constant current element or a light emitting element to indicate energization may be added.

Water-absorbing member Any material can be used as long as it is capable of impregnating and retaining an aqueous ionic drug solution, and suitable examples include water-absorbing paper materials, cloth materials, sponge materials, porous materials, and the like.

USE EXAMPLE One of the usage examples of the structure shown in the attached FIGS. 3 to 5 will be described in more detail as follows.

That is, the conductive gel layer is made of the aforementioned Karaya gum gel or sodium polyacrylate (Aronbis 5), 20% by weight,
Distilled water containing 0% NaCl 15% by weight and glycerin 65%
It is a viscoelastic gel with skin adhesion and has a thickness of 1.5 y and an area of about 24 d, consisting of a N content of The sexual member layer is made of gauze material or polyvinyl formal sponge material with a thickness of about 1.7 mm and an area of about 3 d (hydrophilic gel 19 d).

On the other hand, conductive members for current distribution (51, (71 in this case use aluminum foil), connect the cathode of the button-shaped battery (8) (output voltage 3VX2) directly to the conductor (2), and connect the anode to the lead wire ( 9) is connected to the indifferent conductor (3), and furthermore, the whole is integrally laminated with polyethylene film OI by heat sealing method to provide the plaster structure (1). .

In use, a 10% vitamin C (Na ascorbic acid) containing aqueous solution (stored in ampoules) is added to the water-absorbent layer (4).
The treatment is started by dripping one to several drops and then applying the entire structure to the affected area.

As is well known, vitamin C (ascorbic acid) and its derivatives (sodium ascorbate, etc.) are effective for pigmentation disorders such as melasma, melasma, and various melasma.
Treatments using iontophoresis are already known to be useful in the field of beauty and dermatology, but as mentioned above, they are not widely used due to the complicated operation. However, this example allows the treatment to be performed with extremely simple operations, and can be said to be revolutionary as a treatment or beauty treatment.

In addition, when using the configuration of this example on the face, the amount of current is usually 10 to 80 μA/ffl, and the time it takes for vitamin in C to reach the melanocyte-containing epidermal basal cell layer is about 20 μA/ffl.
~60 minute root degree.

In addition, the plaster structure in this usage example is applied as an analgesic and anti-inflammatory plaster when sodium salicylate or the like is used, but in this case, the so-called flattening method (Ga1 vanization), which has a vasodilatory effect, is also performed. Therefore, it can be understood that it shows a synergistic effect on diseases such as neuralgia, arthralgia, and rheumatoid arthritis.

Some preferred examples of the gel base material for the hydrophilic (conductive) gel layer or adhesive layer of the present invention are as described above, but there are also various hydrophilic polymer materials known as so-called bioelectrode materials, etc. It is once again pointed out that it can be used selectively at will. For example, JP-A-52-95895. 54-774
89゜56-15728. 56-36939 and 56-36940. 57-115252, etc., can be used as the gel base material of the hydrophilic (conductive) gel layer of the present invention by appropriately adjusting the sweetness ratio, etc.

As described above, the gel base material of the hydrophilic (conductive) gel layer of the present invention is a hydrophilic polymer that can be softened and plasticized with water and/or alcohol to give a viscoelastic gel that is adhesive to skin debris. Any material is sufficient, and it is not limited to a specific material, and the composition of the base material is determined by taking into consideration skin adhesion compatibility (and conductivity), etc. Father, these gel layers can be disposable or replaced with other husbands.

Incidentally, it is also possible to add a polarity switching means to the structure in order to freely change the yin and yang of the conductor according to the yin and yang of the effective drug ion species.

Next, a second embodiment of the plaster structure for iontophoresis according to the present invention will be described in detail with reference to FIG. 6 of the drawings. In this embodiment, a sheet battery 09 is used as a lightweight battery. For example, copper foil is placed on one side of this sheet-shaped battery α9.

A current dispersion conductive layer αe (17) made of carbon fiber nonwoven fabric or the like is disposed, and a water absorbent layer (4) for impregnating and retaining an aqueous ionic drug solution is provided at one pole. It is surrounded by a hydrophilic gel layer αB, and a conductive gel layer (6) is laminated on the other pole.

According to the configuration of this embodiment, the sheet battery is 0.5
Since it is extremely thin (m~2m), the thickness of the entire plaster structure ffl is also extremely thin, and a smart plaster structure with no single bulges can be obtained.

Note that the output terminal of the sheet-like battery may be formed into a planar shape, and each output terminal may be used as a conductive layer for distributing current.

In this way, by arranging the skin-adhesive and conductive gel layer around the periphery and edges of the structure in addition to the adhesive properties of the Kando, there is no need for any other fixing means such as adhesive tape. The entire structure is securely fixed to the skin.

If necessary, the water-retentive member layer may be made removable, and the member impregnated with a chemical solution may be placed at a predetermined position in the structure at the time of use and used for treatment. Also, instead of the water-absorbing material, agar gel,
It is clear that non-adhesive hydrogels commonly used in the field of electrophoresis, such as gelatin gels, may also be used. An example of an agar water gel composition is as follows.

This type of hydrogel piece may be placed in advance on the structure, or may be placed in use as described above.

Furthermore, each side above shows the case where a non-conductor is provided at the periphery of the structure, but if sufficient skin adhesion is imparted to the hydrophilic gel layer of the non-conductor, the two can be separated to the left and right, creating a backing. It may be a simple form connected by.

Furthermore, in both of the above two examples, the hydrophilic gel layer (
If the conductivity of Il+ is made relatively small, or as a barrier 4
By providing this, it may be connected and integrated with the conductive gel layer (6) without separating it.

In addition, it is clear that the indifferent conductor may also have the same structure as the inventive conductor.

In this case, since a conductive gel is no longer required, two water-absorbing members are attached to one sheet of a hydrophilic gel material (adhesive material) with low conductivity through an insulating barrier tJs, a. It is sufficient if they are spaced apart from each other, as shown in FIG. 7.

That is, FIG. 7 shows an insulating barrier (IL) having water absorbing members (41, +41) on one sheet of hydrophilic gel material (4).
This is an example in which two drug reservoirs formed by α2 are arranged, and the conductive members (5) and (7) [on the aqueous member of both eyes are electrically connected to each other's poles of the button battery 8. There is.

Furthermore, in this example, as the hydrophilic gel layer α1), a general hydrophilic adhesive (JP-A-49-15731, JP-A-54) is used.
-70340, etc.) can be used, and the present invention also encompasses these.

In addition, in FIG. 7, the punching a1 other than the drug solution reservoir portion is made thicker to form a drug solution reservoir space,
The surface may be coated with a relatively thin hydrophilic adhesive to form the gel layer α1).

Alternatively, the insulating barrier layer a may be integrally molded with the backing.

Furthermore, the hydrophilic gel layer (111) may be formed only around the chemical reservoir, and the remaining portion may be replaced with an ordinary non-hydrophilic adhesive.

Although we have described in detail an example in which both conductors are placed close to each other, there may be cases where it is more convenient to separate the conductor and the conductor from each other depending on the attachment site. In this case, it is sufficient to simply electrically connect the two using lead wires and stack the lightweight batteries on either or both of them. Therefore, in the present invention, the terms ``integral molding'' and ``integral connection'' include not only the case where they are disposed on the same backing, but also the case where they are connected in a sleepy manner in general. It is.

Furthermore, as the water-absorbing member of the present invention, gels such as the aforementioned poly(acrylic acid-acrylamide) gel, vinyl alcohol gel, polyvinylpyrrolidone gel, etc., which have a substantially high resistance (for example, 100Ω·α or more) may be used. may also be used; in this case, impregnation with the chemical solution lowers the resistance value of the gel, making it possible to perform iontophoresis efficiently. Particularly in this case, since these gels have skin adhesive properties (σ), they may be used to form a hydrophilic gel layer, and one continuous gel layer may constitute the skin contact surface of the Kando element.

As is clear from the above, the conductor or plaster structure of the present invention allows iontophoresis, which is an effective method for promoting casting, to be performed with a significantly simple operation, does not require complicated and large equipment, and is safe. It is highly effective in ensuring that people can provide relief.

[Brief explanation of the drawing]

1 and 2 are explanatory schematic diagrams of the conductor of the present invention, and FIG. 1 is a plan view thereof, and FIG. 2 (a cross-sectional view of the core). 5 shows a bottom view. FIG. 6 shows a sectional view of the second embodiment. FIG. 7 shows a sectional view of the third embodiment. (1 )・・・Plaster structure for iontophoresis (2)・・・Seki conductor, (3)・・・・・・Inkan conductor. (4)・・・・・・Water-absorbing material layer for impregnating with ionic liquid. (5), αe... Conductive material layer for current dispersion of seki conductors. (6)... Skin adhesive conductive gel layer (71, (17)... Conductive material layer for current dispersion of the indifferent conductor. (8)... Button-shaped battery (lightweight battery). 09... Sheet battery (lightweight battery) and (Ill...hydrophilic gel layer) Patent applicant: Advance Development Institute Co., Ltd. Figure 1 Figure 2 Figure 3 Upper Figure 4

Claims (3)

[Claims] (1) A water-absorbing member for impregnating an ionic chemical solution or an electrolyte solution that is brought into contact with the conductive member layer for current dispersion, and a water-absorbing member for impregnating the medicinal solution impregnated with this member and surrounding it at least around the area in order to seal and hold the drug solution impregnated on the skin. An iontophoresis conductor comprising a hydrophilic adhesive or gel layer having skin adhesive properties and a backing layer integrally laminated thereon. (2) Combination of the above conductor as a conductor, a conductor formed by integrally laminating a conductive gel layer with skin adhesion and a conductive material layer for current dispersion, and a lightweight battery. The combined structure has a structure in which each conductor is arranged so as to be integrally adhered and fixed to the skin by the skin adhesive property of the conductive gel layer, and the conductor is arranged to be fixed to the skin by the skin adhesion of the conductive gel layer. A plaster structure for iontophoresis, characterized in that each of the conductors is electrically connected to the lightweight battery so as to form a closed circuit. (3) Claim No. (11) A Branuter structure for iontophoresis, which is formed by integrally connecting the two conductors and a lightweight battery.