Biodegradable iontophoretic patch and manufacturing method therefor

Abstract

The present invention relates to a biodegradable iontophoretic patch and a manufacturing method therefor, the iontophoretic patch comprising a drug-loading gel and a buffering gel, wherein the addition of a pH regulator to the buffering gel can prevent an excessive increase in PH value according to the use of the iontophoretic patch, and thus the present invention can be used for manufacturing an iontophoretic patch for skin absorption of a cosmetic composition or a pharmaceutical composition.

Description

Biodegradable ion patch and method for manufacturing the same

[0001] The present invention relates to a biodegradable ion patch and a method for manufacturing the same, and more particularly, to a technology for providing an ion patch manufactured from a biodegradable material, which comprises a drug-loading gel and a buffering gel, and by adding a pH adjusting agent to the buffering gel, the pH value can be prevented from increasing excessively due to use of the ion patch.

[0002]

[0003] Iontophoresis is a technology that uses microcurrents to flow through the skin, allowing charged substances of interest to penetrate the skin through electrical repulsion. Iontophoresis patches utilize this electrical repulsion to penetrate substances of interest, such as drugs or cosmetic ingredients, into the skin. When a patch loaded with a substance of interest is attached to the skin, a circuit is formed, causing current to flow, and the substance of interest penetrates the skin through electrical repulsion. The rate of penetration of the substance of interest is known to be directly affected by the amount of current flowing through the skin.

[0004] Conventional iontophoresis devices typically attach two electrodes to the skin, each connected to an electrical device via a wire. The substance of interest is placed on the electrode surface, and when the device is activated, the substance penetrates the body. The device is designed to control the amount and duration of the current. However, the problem with these systems is that the patient is connected to the device via a wire, restricting their daily movements and activities.

[0005] In addition, it is vulnerable to the preservation of the installed battery, and the assembly process is complicated, resulting in low productivity and increased prices. In addition, because it goes through a multi-step reaction process, its efficacy is low, limiting the penetration of cosmetics or drugs into the skin.

[0006] Recent patch-type iontophoresis systems have been developed to integrate electrical circuitry and current supply into a single patch. These systems consist of an iontophoresis patch and a battery electrically connected to form a single patch. This is considered a significant advancement over the existing method of supplying power externally via wires.

[0007] Accordingly, the inventors of the present invention confirmed that the drug is loaded into a drug-loading gel laminated on the cathode, and a pH regulator is included in a buffering gel laminated on the anode to lower the pH value and simultaneously buffer the pH change, thereby having an excellent effect of suppressing an excessive increase in the pH value when used by attaching an ion patch.

[0008] Accordingly, an object of the present invention is to provide an ion patch comprising a plate-shaped frame; an electrode layer including electrodes laminated on the frame; and a gel layer including a gel laminated on the electrodes.

[0009] Another object of the present invention is to provide a method for manufacturing an ion patch comprising the following steps:

[0010] An electrode layer forming step of laminating electrodes on a plate-shaped frame; and

[0011] A gel layer forming step of laminating a gel on the above electrode.

[0012]

[0013] The present invention relates to a biodegradable ion patch and a method for manufacturing the same. The ion patch according to the present invention comprises a drug-loading gel and a buffering gel, and by adding a pH regulator to the buffering gel, the pH value can be prevented from increasing excessively due to use of the ion patch.

[0014] Hereinafter, the present invention will be described in more detail.

[0015]

[0016] One aspect of the present invention is an ion patch comprising: a plate-shaped frame; an electrode layer including electrodes laminated on the frame; and a gel layer including a gel laminated on the electrodes.

[0017] Another aspect of the present invention comprises an electrode layer including a pair of positive and negative electrodes; and gel layers performing different functions, each of which is laminated on the positive and negative electrodes; wherein the gel laminated on the positive electrode may be a buffering gel including a pH adjusting agent, and the gel laminated on the negative electrode may be a drug-loading gel.

[0018] The above ion patch may further include a frame positioned below the electrode, and the frame may include a biodegradable polymer. The biodegradable polymer constituting the frame may include polybutylene adipate-co-terephthalate (PBAT).

[0019]

[0020] The following means may be added to each of the above aspects one or more times to form each embodiment.

[0021] In the present invention, the electrode layer may include a cathode and an anode disposed spaced apart from the cathode.

[0022] In the present invention, the cathode and anode may each independently have a thickness of 50 to 400 μm.

[0023] Preferably, the cathode may have a thickness of 50 to 350 μm, 50 to 300 μm, 100 to 400 μm, 100 to 350 μm, 100 to 300 μm, 150 to 400 μm, 150 to 350 μm, 150 to 300 μm, 200 to 400 μm, or 200 to 350 μm, for example, but not limited to, 200 to 300 μm.

[0024] Also preferably, the anode may have a thickness of 50 to 350 μm, 50 to 300 μm, 50 to 200 μm, 50 to 150 μm, 100 to 400 μm, 100 to 350 μm, 100 to 300 μm, 100 to 250 μm, or 100 to 200 μm, for example, but not limited to, 100 to 150 μm.

[0025] In the present invention, the gel laminated on the cathode and the gel laminated on the anode may be arranged spaced apart from each other.

[0026] In the present invention, the gel layer laminated on the cathode and the gel layer laminated on the anode may each independently have a thickness of 0.4 to 2 mm, preferably a thickness of 0.4 to 1.5 mm, 0.4 to 1.2 mm, 0.4 to 1 mm, 0.8 to 2 mm, 0.8 to 1.5 mm, or 0.8 to 1.2 mm, and for example, a thickness of 0.8 to 1 mm, but is not limited thereto.

[0027] In the present invention, the cathode comprises a biodegradable material capable of a skin-friendly reduction reaction, and may comprise at least one of a transition metal oxide, a metal, and a biodegradable polymer. The cathode may be made of molybdenum trioxide (MoO3), but is not limited thereto.

[0028] Since the above molybdenum trioxide is formed by inserting Na+ ions, etc. into the lattice structure during the electrochemical reaction process, side reactions such as pH changes can be suppressed because H+ or OH- are not consumed. Therefore, these reactions can be defined as skin-friendly reduction reactions. In the present invention, not only molybdenum trioxide, but also any material that suppresses side reactions can be used as an anode material.

[0029] In the present invention, the negative electrode may include a biodegradable polymer and a crosslinking agent.

[0030] Because the biodegradable polymer described above is hydrophilic, water can readily be absorbed into it. Previously, when using such biodegradable polymers, the electrolyte water would seep into the ion patch during operation, causing swelling. This caused the polymer to loosen its grip on the cathode material and become loose. This hindered electron transfer to the cathode material, disrupting normal electrochemical reactions and resulting in performance degradation.

[0031] On the other hand, in the above embodiment, a cross-linking agent is added to the polymer to suppress movement and expansion of the biodegradable polymer, while at the same time allowing the biodegradable polymer to hold the negative electrode material well during operation, thereby maintaining performance.

[0032]

[0033] The cathode may include a biodegradable conductive material-based coating on the contact surface with the frame. The coating may include, but is not limited to, a coating material including molybdenum (Mo) or titanium (Ti).

[0034] The coating material may have a thickness of 5 to 30 μm, preferably 5 to 25 μm, 5 to 20 μm, 5 to 15 μm, 10 to 30 μm, 10 to 25 μm, or 10 to 20 μm, for example, but is not limited thereto.

[0035] In the present invention, the gel laminated on the cathode may be a drug-loading gel containing a loaded drug.

[0036] The above-mentioned drug may be at least one selected from the group consisting of caffeine, niacinamide, and adenosine, but is not limited thereto.

[0037] In the present invention, the anode may include a biodegradable metal. The anode may be made of magnesium (Mg), but is not limited thereto.

[0038] In the present invention, the gel laminated on the anode may be a buffer gel containing a pH regulator, and the pH regulator may be citric acid.

[0039] The citric acid may be included in the buffer gel in an amount of 150 to 500 mM, preferably 150 to 400 mM, 150 to 300 mM, 150 to 250 mM, 200 to 500 mM, 200 to 400 mM, 200 to 300 mM, 200 to 250 mM, 250 to 500 mM, or 250 to 400 mM, for example, but not limited to, 250 to 300 mM.

[0040] In the present invention, the electrode layer may additionally include a current regulator connecting the cathode and the anode.

[0041] The current controller may be made of a mixture of biodegradable metal particles and biodegradable polymers. The current controller may include, but is not limited to, molybdenum (Mo) or titanium (Ti). The current controller may function as a resistor based on a mixture of biodegradable metal particles and biodegradable polymers at a certain ratio. The current controller may be capable of controlling conductivity by adjusting the volume ratio of the internal particles, etc.

[0042] The above current regulator may be a mixture of PBAT (Polybuthylene Adipate-co-Terephthalate), but is not limited thereto.

[0043] In the present invention, the concentration of metal particles in the current regulator may be 10% to 40% by volume.

[0044] In addition, in the present invention, the gel layer may be formed of two or more layers each independently including two or more kinds selected from the group consisting of alginate, gelatin, agar, maltose, and glycerol, and for example, may be formed of two layers each independently including gelatin and agar, but is not limited thereto. The function of each layer will be described in more detail below.

[0045] In the present invention, the drug-carrying gel may include at least one selected from a group of biodegradable ionic polymers such as alginate, CMC (carboxymethyl cellulose), and DS (dextran sulfate).

[0046] The biodegradable ionic polymer used in the above drug-loading gel is COO - , SO3 2-It may include a functional group that carries an ion. When a drug carrying a counter ion (+) is loaded on such an ionic polymer, when the ion patch is operated, only the movement of the + ion that was dependent on the drug carrying a + ion and the ionic functional group of the polymer is possible, so the movement of the ion can be possible in only one direction.

[0047] Because ions move by adsorbing water, controlling ion movement in one direction also controls water flow in one direction. This phenomenon is called electroosmosis. In the present invention, the water flow generated by this osmosis can also transport drugs dissolved within it, allowing for the delivery of significantly more drugs using the same amount of power.

[0048] In the present invention, the buffering gel may independently contain at least one selected from the group consisting of agarose, maltose, and glycerol. It is preferable to use a biodegradable polymer with good ion conductivity as the polymer used in the buffering gel.

[0049] In the present invention, the concentration of the gel may be 2 to 10 wt%, preferably 2 to 8 wt%, 2 to 6 wt%, 2 to 4 wt%, 4 to 10 wt%, or 4 to 8 wt%, for example, 4 to 6 wt%, but is not limited thereto.

[0050] In the present invention, at least one of the drug-carrying gel layer and the buffering gel layer may further include a skin-adhesive gel layer, and the skin-adhesive gel layer may include gelatin and an ion-conductive biodegradable polymer.

[0051] Gels such as agar or alginate lack adhesive properties, which can easily detach when applied to the skin, potentially reducing operational stability. Therefore, layering a gelatin-based gel layer with excellent skin adhesion onto the area in contact with the skin can improve skin adhesion. The appropriate concentration of gelatin within the gel layer may range from 1% to 4% by weight.

[0052] However, using gelatin alone as the gel layer can be problematic due to the low ionic conductivity of the gelatin-based gel. This reduces the current of the ion patch, which can reduce the drug delivery rate. Therefore, in the above embodiment, a skin-adhesive gel layer was introduced in a laminated structure on the side where the gel layer touches the skin to ensure adhesiveness while maintaining a high drug delivery rate.

[0053]

[0054] Another aspect of the present invention is a method for manufacturing an ion patch, comprising the following steps:

[0055] An electrode layer forming step of laminating electrodes on a plate-shaped frame; and

[0056] A gel layer forming step of laminating a gel on the above electrode.

[0057] In the present invention, the frame may be PLGA or PGLA.

[0058] In the present invention, the electrode layer forming step may be forming a cathode and an anode spaced apart from the cathode.

[0059] The above cathode may be made of molybdenum trioxide (MoO3), but is not limited thereto.

[0060] The above cathode may additionally include a coating material of molybdenum (Mo) or titanium (Ti) on the contact surface with the frame, but is not limited thereto.

[0061] The above anode may be made of magnesium (Mg), but is not limited thereto.

[0062] In the present invention, the gel layer forming step may be to arrange the gel laminated on the cathode and the gel laminated on the anode so as to be spaced apart from each other.

[0063] The gel laminated on the above cathode may be a drug-loading gel containing a loaded drug.

[0064] The gel laminated on the above anode may be a buffer gel containing a pH regulator, and the pH regulator may be citric acid.

[0065] In the present invention, the manufacturing method may additionally include a current regulator forming step of additionally forming a current regulator connecting the cathode and the anode.

[0066] The above current regulator may be made of, but is not limited to, molybdenum (Mo) or titanium (Ti).

[0067] The above current regulator may be coated with PBAT, but is not limited thereto.

[0068] In the present invention, the gel layer forming step may be performed by laminating one or more selected from the group consisting of alginate, gelatin, agar, maltose, and glycerol, and may be, for example, laminating alginate, but is not limited thereto.

[0069] In the present invention, the gel layer forming step may be performed by laminating two or more layers each independently including two or more kinds selected from the group consisting of alginate, gelatin, agar, maltose, and glycerol, and for example, may be performed by laminating two layers each independently including gelatin and agar, but is not limited thereto.

[0070]

[0071] The present invention relates to a biodegradable ion patch (iontophoretic patch) and a method for manufacturing the same. The ion patch comprises a drug-loading gel and a buffering gel, and a pH adjusting agent is added to the buffering gel to prevent the pH value from increasing excessively when the ion patch is used. Therefore, the ion patch can be used for manufacturing an ion patch for skin absorption of a cosmetic composition or a pharmaceutical composition.

[0072]

[0073] Figure 1a is a schematic diagram of an ion patch manufactured according to one embodiment of the present invention.

[0074] FIG. 1b is a graph of current signals measured from ion patches manufactured by varying the thickness of MoO3 according to one embodiment of the present invention.

[0075] FIG. 2a is a schematic diagram and photograph of an ion patch manufactured by selecting a thickness of MoO3 paste of 300 μm according to one embodiment of the present invention.

[0076] FIG. 2b is a graph of a current signal measured from an ion patch manufactured by selecting a thickness of MoO3 paste of 300 μm according to one embodiment of the present invention.

[0077] FIG. 2c is a discharge graph measured from an ion patch manufactured according to one embodiment of the present invention, depending on whether citric acid, a cross-linking agent, was added to MoO3 and PAAc (polyacrylic acid) polymer paste.

[0078] FIG. 2d is an image showing the presence or absence of diffusion of the negative electrode material due to polymer swelling after discharging an ion patch manufactured according to one embodiment of the present invention with or without the addition of citric acid, a cross-linking agent, to MoO3 and PAAc (polyacrylic acid) polymer paste for 1 hour at a current of 300 uA.

[0079] FIG. 3a is a schematic diagram of an ion patch in which the cathode is coated with molybdenum (Mo) according to one embodiment of the present invention.

[0080] Figure 3b is a graph confirming the pH value change by an ion patch in which the cathode is coated with molybdenum under conditions of pH 7.4 according to one embodiment of the present invention.

[0081] Figure 3c is a graph confirming the pH value change by an ion patch in which the cathode is coated with molybdenum under conditions of pH 5.5 according to one embodiment of the present invention.

[0082] Figure 4a is a diagram showing the pH value of the skin surface according to the part of the human body.

[0083] Figure 4b is a graph confirming the change in pH value by an ion patch under the condition of pH 4.2 according to one embodiment of the present invention.

[0084] Figure 5a is a schematic diagram of an ion patch for checking whether pH is adjusted by adding citric acid according to one embodiment of the present invention.

[0085] Figure 5b is a schematic diagram of an ion patch showing a measurement site for pH control by the addition of citric acid according to one embodiment of the present invention.

[0086] FIG. 6a is a schematic diagram of an ion patch and a skin model for confirming drug absorption rate into the skin by current density according to one embodiment of the present invention.

[0087] Figure 6b is a graph showing the drug absorption rate from an ion patch to the skin according to current density according to one embodiment of the present invention.

[0088] FIG. 7a is a schematic diagram of an electrode structure and a skin model for confirming the drug absorption rate from an ion patch to the skin depending on whether iontophoresis is applied according to one embodiment of the present invention.

[0089] Figure 7b is a graph confirming the drug absorption rate from an ion patch to the skin depending on whether iontophoresis is applied according to one embodiment of the present invention.

[0090] Figure 8a is a graph confirming the absorption rate of niacinamide into the skin from an ion patch depending on whether iontophoresis is applied according to one embodiment of the present invention.

[0091] Figure 8b is a graph confirming the rate of adenosine absorption into the skin from an ion patch depending on whether iontophoresis is applied according to one embodiment of the present invention.

[0092] Figure 9a is a schematic diagram of a single-gel and double-gel application ion patch model according to one embodiment of the present invention.

[0093] Figure 9b is a current intensity graph by a single-gel and double-gel application ion patch model according to one embodiment of the present invention.

[0094] Figure 10a is a current intensity graph by a gelatin gel application ion patch model according to one embodiment of the present invention.

[0095] Figure 10b is a current intensity graph by an ion patch model applied with alginate gel according to one embodiment of the present invention.

[0096] Figure 11a is a schematic diagram of a type-specific gel application ion patch model according to one embodiment of the present invention.

[0097] Figure 11b is a graph comparing the ion absorption amounts of gelatin and alginate-applied ion patch models according to one embodiment of the present invention.

[0098] Figure 12a is a schematic diagram of an ion patch model and a skin model for measuring ion absorption at different skin depths according to one embodiment of the present invention.

[0099] Figure 12b is a graph showing the measurement of ion absorption of a drug-bearing gel according to one embodiment of the present invention.

[0100] Figure 13 is a schematic diagram of an ion patch manufactured according to one embodiment of the present invention.

[0101]

[0102] Hereinafter, the present invention will be described in more detail with reference to the following examples. However, these examples are only intended to illustrate the present invention, and the scope of the present invention is not limited by these examples.

[0103] Throughout this specification, "%" used to indicate the concentration of a particular substance is (wt / wt)% for solid / solid, (wt / vol)% for solid / liquid, and (vol / vol)% for liquid / liquid, unless otherwise stated.

[0104]

[0105] Example 1: Composition of ion patch

[0106] In order to select an appropriate thickness for using molybdenum trioxide (MoO3) as an electrode in the configuration of an ion patch, electrode structures were manufactured with thicknesses of 150, 200, and 400 μm, respectively, and the current signal was measured using an amperemeter.

[0107] As can be seen in Figures 1a and 1b, as the thickness of MoO3 increases, the current capacity increases and the degree of ion diffusion decreases, so the thickness condition of 200 μm was determined to be the best.

[0108] Next, a model capable of implementing ion patch operation was fabricated as shown in Fig. 2a by selecting the thickness of MoO3 used as the cathode as 300 μm, and the current signal was measured.

[0109] As can be seen in Fig. 2b, the current capacity measured in the ion patch operation implementation model is 0.486 mA*h, which is higher than the value of 0.15 mA*h required for iontophoresis, and it can be judged that a microcurrent within an appropriate range can be generated.

[0110]

[0111] Example 2: Ensuring operational stability using a cross-linking agent

[0112] The electrolyte-based galvanic ion patch, consisting of a cathode material and a polymer binder, has a problem in that the cathode absorbs moisture due to the polymer's hydrophilicity, causing swelling and reduced operational stability. To partially address this issue, a cross-linking agent can be used.

[0113] As can be seen in Fig. 2c, the difference depending on the presence or absence of the cross-linking agent, citric acid, is that when no cross-linking agent is used, the negative electrode material becomes loose and spreads over time due to the expansion of the polymer binder, which causes the electrochemical reaction occurring at the negative electrode to become unstable, resulting in a decrease in the operating voltage. On the other hand, when a cross-linking agent is used, the negative electrode material remains stably fixed to the polymer binder over time, resulting in a stable electrochemical reaction and maintaining the operating voltage.

[0114] As can be seen in Fig. 2d, when a cross-linker is not used, the negative electrode material diffuses and spreads out inside the electrolyte after operation, whereas when a cross-linker is used, the negative electrode material is fixed even after operation.

[0115]

[0116] Example 3: Conditioning the pH value within the ion patch

[0117] Ion patches have a problem in that the pH value at the anode may increase as they operate. To partially compensate for this, a method of coating the cathode of MoO3 with molybdenum (Mo) can be used, as shown in Fig. 3a.

[0118] As can be seen in Figure 3b, the difference according to the resulting measured pH value can be seen when the pH value is 7.4, as MgO2 increases on the anode surface, OH- is generated within the electrolyte, which can increase the pH value. From this, it can be inferred that reducing the generation of MgO2 on the electrode surface can be a way to prevent the increase in pH value.

[0119] As can be seen in Fig. 3c, when applied to a case where the pH value is actually low as 5.5, the generation of MgO2 on the anode surface is suppressed, so OH- is not generated in the electrolyte, and accordingly, the pH value does not increase.

[0120]

[0121] Example 3: Exploring Optimal Conditions for pH Values

[0122] As can be seen in Fig. 4a, based on biocompatibility based on the face, which is the attachment site of the ion patch, the pH value is appropriate to be 4.2, so the application conditions of the electrode structure were adjusted in this way.

[0123] As can be seen in Fig. 4b, the application results of the electrode structure under pH 4.2 conditions are the same as those under the pH 5.5 conditions, but Mg 2+ The ion levels were found to be stable.

[0124] As a method for controlling the pH value, 250 mM citric acid was added to the gel laminated on the anode, and a case in which citric acid was not added was used as a control.

[0125]

[0126] Gelatin gelPBSglycerolsugar syrupCitrateCitrate concentrationpHCitrate8 ml6.3 ml6.5 ml1 g250 mM3Control8 ml6.3 ml6.5 ml0 g0 mM7.4

[0127]

[0128] The conditions of the electrode structures shown in Figures 5a and 5b are as follows:

[0129] Current: 100 μA

[0130] Time: 1 hour

[0131] Gelatin gel volume: 0.08 cm 3

[0132] OH on the Mg surface - Amount measured: 3.73 μmol

[0133] Measurement of citric acid content in gelatin gel: (Control: 0 mol; Article condition: 20 μmol; Harsh condition: 40 μmol)

[0134]

[0135] pH @ Mg - Gelatin pH @ Gelatin - Agar Citric acid added 33 Control group (no citric acid added) 9.5 ~ 108

[0136]

[0137] As can be confirmed in Table 2 above, the results of the analysis in the model that implemented the operation of the ion patch showed that the pH value was consistently measured as 3 regardless of the measurement site in the ion patch containing the gel with added citric acid, but in the case where citric acid was not added, the pH value was confirmed to be 8 or 9.5, or as high as 10, depending on the measurement site. From this, it can be determined that the addition of citric acid effectively suppresses the increase in the pH value.

[0138]

[0139] Example 4: Optimization of current density to maximize drug absorption.

[0140] To enhance the absorption efficiency of the drug contained in the gel, the current density applied to the ion patch was adjusted. Specifically, caffeine was added to the gelatin gel laminated to the positive electrode of the ion patch, and current densities of 50, 100, and 150 μA were applied. The amount of caffeine absorbed through the skin was measured and compared.

[0141] As can be seen in Figures 6a and 6b, the amount of caffeine absorbed was high in the order of current densities of 150, 50, and 100 μA, and in particular, the highest absorption rate was observed at 150 μA, so it was estimated that the most ideal current density for application to the ion patch was 150 μA.

[0142]

[0143] Example 5: Comparison of drug absorption rates in patches depending on whether iontophoresis is applied.

[0144] In order to compare the difference in the absorption rate of the drug loaded in the patch depending on whether iontophoresis was applied, the amount of drug absorbed by the ion patch and reaching the inside of the tissue was measured at points 5 and 10 mm from the skin surface, respectively, using human skin.

[0145] As shown in Figures 7a and 7b, even at the 5 mm point, the ion patch exhibited a higher drug absorption rate than the control group. In particular, at the 10 mm point, almost no drug was absorbed from the control group, whereas a constant amount of drug was absorbed from the ion patch. This confirms that the drug absorption rate and depth of drug penetration into the skin are also excellent when iontophoresis is applied.

[0146] Next, the degree of skin absorption of the active ingredients was confirmed from a skin whitening ion patch equipped with a gel containing niacinamide and a skin aging inhibition ion patch equipped with a gel containing adenosine.

[0147] As can be seen in Figures 8a and 8b, it was confirmed that the absorption amount of the active ingredient was significantly superior to that of the control group when iontophoresis was applied.

[0148]

[0149] Example 7: Optimization of the structure and composition of the gel

[0150] 7-1. Ion absorption control by double gel structure

[0151] In creating a model for implementing the operation of the ion patch, a model using gelatin gel and a model using a double gel by adding agar gel to the gelatin gel were prepared as shown in Fig. 9a.

[0152] As can be seen in Fig. 9b, in the double gel application model with added agar gel, the absorption of ions is slowed and the intensity of the current is also lowered, so by applying this configuration, the amount of drug absorption can be controlled as needed.

[0153]

[0154] 7-2. Control of ion absorption according to gel material

[0155] In manufacturing the electrode structure, the changes that occur when the gel material is replaced with alginate instead of gelatin were also compared and confirmed.

[0156] As can be seen in Figures 10a and 10b, it was confirmed that when the alginate gel was used, ion diffusion increased and the current intensity became stronger compared to when the gelatin gel was used.

[0157]

[0158] 7-3. Control of ion absorption according to electrode selection

[0159] Depending on which electrode, the cathode or anode, is selected to laminate the drug-loading gel, the degree to which the active ingredient is absorbed into the skin from the laminated gel was analyzed.

[0160] Specifically, the amount of ion absorption was measured by applying an electrolyte gel made of gelatin or alginate to the cathode and anode, respectively.

[0161] As can be seen in Figures 11a and 11b, the alginate gel was stable at a current of 200 μA for 2 hours, and especially when used at the cathode, the diffusion rate increased compared to the control group (passive) as well as when used at the anode, resulting in a significantly higher content of absorbed ions. On the other hand, in the case of gelatin gel, which has a current of 50 μA and a limited usable time of 1 hour, the amount of ion absorption was almost zero compared to the alginate gel.

[0162] This is believed to be because the inherent dispersion coefficient of alginate is high, so delivery by iontophoresis is dominant.

[0163] Next, as shown in Fig. 12a, the types of electrodes laminated with the drug-loading gel were changed, and the extent to which the drug loaded in the gel was absorbed into the skin was measured and compared at depth levels of 0 to 1, 2 to 3, and 4 to 5 mm.

[0164] As shown in Figure 12b, the amount absorbed from the gel to the skin surface from both the cathode and anode was similar. However, a comparison of the ion content reaching a depth of 5 mm confirmed that only ions absorbed from the gel layered on the cathode were present.

[0165] As a result, a biodegradable ion patch as shown in Fig. 13 was derived.

Claims

1. An electrode layer comprising a pair of positive and negative electrodes; It includes gel layers each performing different functions laminated on the positive and negative electrodes; The gel laminated on the above anode is a buffer gel containing a pH regulator, The gel laminated on the above cathode is a drug-bearing gel. Ion patch.

2. In the first paragraph, the ion patch further includes a frame positioned below the electrode, The above frame is an ion patch containing a biodegradable polymer, PBAT (polybutylene adipate-co-terephthalate).

3. An ion patch according to claim 1, wherein the cathode and anode each independently have a thickness of 50 to 400 μm.

4. An ion patch according to claim 1, wherein the gel layer laminated on the cathode and the gel layer laminated on the anode each independently have a thickness of 0.4 to 2 mm.

5. An ion patch according to claim 1, wherein the cathode comprises a biodegradable material capable of a skin-friendly reduction reaction, and comprises at least one of a transition metal oxide, a biodegradable metal, and a biodegradable polymer.

6. In the first paragraph, the negative electrode comprises a biodegradable polymer and a crosslinking agent, an ion patch.

7. An ion patch according to claim 2, wherein the cathode additionally includes a coating material based on a biodegradable conductive material on a contact surface with the frame.

8. An ion patch according to claim 1, wherein the positive electrode comprises a biodegradable metal.

9. An ion patch according to claim 1, wherein the electrode layer additionally includes a current regulator connecting the cathode and the anode.

10. An ion patch according to claim 9, wherein the current controller is made of a mixture of biodegradable metal particles and biodegradable polymers.

11. An ion patch according to claim 1, wherein the drug-carrying gel comprises at least one selected from a group of biodegradable ionic polymers such as alginate, CMC (carboxymethyl cellulose), and DS (dextran sulfate).

12. An ion patch according to claim 1, wherein the buffering gel independently comprises at least one selected from the group consisting of agarose, maltose, and glycerol.

13. In the first paragraph, at least one of the drug-bearing gel layer and the buffering gel layer further includes a skin-adhesive gel layer, An ion patch, wherein the skin adhesive gel layer comprises gelatin and an ion-conductive biodegradable polymer.

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