Hydrogel sheet, and iontophoresis method using the hydrogel sheet

Abstract

To provide an excellent hydrogel sheet that can be handled easily as an electric conductive sheet for an ion introduction method and has high adhesion to skin, and a use method thereof.SOLUTION: A hydrogel sheet contains a water-soluble polymer, glycerol, a crosslinker, and water. In a preferable embodiment, the hydrogel sheet is for electric conduction by the ion introduction method. In another preferable embodiment of the hydrogel sheet, the content of the water-soluble polymer is 3-30 mass% relative to the total amount of the hydrogel.SELECTED DRAWING: None

Description

【Technical Field】 【0001】 The present invention relates to a hydrogel sheet and an ion introduction method. 【Background Art】 【0002】 In recent years, for medical and cosmetic purposes, an ion introduction method for permeating various medicinal components and the like into skin tissues has been used in medical settings, particularly in dermatology, cosmetic dermatology, and the cosmetic formation field. In the ion introduction method, a conductive sheet mainly composed of alginate is widely used in medical settings. 【0003】 Conventionally, regarding electrode sheets for ion introduction methods or iontophoresis, conductive gels containing various components have been studied (Patent Documents 1 to 3). 【Prior Art Documents】 【Patent Documents】 【0004】 【Patent Document 1】 Japanese Patent Laid-Open No. 63-92683 【Patent Document 2】 Japanese Patent Laid-Open No. 2018-24608 【Patent Document 3】 Japanese Patent Laid-Open No. 2020-103703 【Summary of the Invention】 【Problems to be Solved by the Invention】 【0005】 However, in the ion introduction method in the fields of dermatology, cosmetic dermatology, and cosmetic formation, including the above-described conventional technologies, when using a sheet-like application of alginic acid as a conductive agent (hereinafter, sometimes referred to as an "alginate mask" when used during treatment), the following problems have occurred. (1) Since alginate is a natural material, its quality is unstable. (2) Since the alginate mask is prepared at the time of use, it takes time to prepare. (3) When alginate is made into a sheet, it tends to become uneven. (4) When applying alginate, it may run off. (5) Alginates produce a distinctive odor. (6) In recent years, it has become difficult to obtain high-quality alginate. (7) In the case of alginate masks, adhesive residue is observed after peeling. 【0006】 Therefore, given the shortcomings of alginate masks, there is a need for superior conductive sheets to replace them in medical settings. 【0007】 Furthermore, none of the aforementioned Patent Documents 1-3 meet the requirements for ease of handling and good adhesiveness. In addition, in the fields of dermatology, cosmetic dermatology, and cosmetic plastic surgery, a good feel (adhesion) is required during procedures, and currently, no suitable product has been found that satisfies this requirement. 【0008】 Therefore, the present invention aims to solve the problems of the conventional method and provide a hydrogel sheet that can be easily handled as a conductive agent for iontophoresis, has high adhesion to the skin, and is excellent in terms of its use. [Means for solving the problem] 【0009】 In order to solve the above problems, the inventors of this invention conducted thorough research on hydrogel sheets and, as a result, completed the present invention. 【0010】 In other words, the hydrogel sheet of the present invention is a hydrogel sheet containing a water-soluble polymer, glycerin, a crosslinking agent, and water. The hydrogel sheet is formed between a support layer made of nonwoven fabric and a plastic film, and the hydrogel sheet is for conductivity by ion introduction. It is characterized by the following: 【0011】 Furthermore, in a preferred embodiment of the hydrogel sheet of the present invention, The aforementioned plastic film is made of polyethylene, polypropylene, polyester, or polyvinyl chloride. It is characterized by the following: 【0012】 Also, in a preferred embodiment of the hydrogel sheet of the present invention, the blending amount of the water-soluble polymer is 3 to 30% by mass based on the total amount of the hydrogel. 【0013】 Also, in a preferred embodiment of the hydrogel sheet of the present invention, the blending amount of the glycerin is 5 to 50% by mass based on the total amount of the hydrogel. 【0014】 Also, in a preferred embodiment of the hydrogel sheet of the present invention, the blending amount of the crosslinking agent is 0.001 to 1% by mass based on the total amount of the hydrogel. 【0015】 Also, in a preferred embodiment of the hydrogel sheet of the present invention, the blending amount of the water is 30 to 85% by mass based on the total amount of the hydrogel. 【0016】 Also, in a preferred embodiment of the hydrogel sheet of the present invention, it further contains an active ingredient. 【0017】 Also, of the present invention The conductive sheet is a conductive sheet used in the ion introduction method, and the conductive sheet is, The hydrogel sheet of the present invention That is is characterized by this. 【0018】 Also, of the present invention The conductive sheet is a conductive sheet used in the ion introduction method, and the conductive sheet is, The hydrogel sheet of the present invention And, On the side of the conductive sheet where it is adhered, Apply the active ingredient is provided with an active ingredient layer. 【Advantages of the Invention】 【0019】 The hydrogel sheet of the present invention has an advantageous effect that it can be used as a conductive sheet simply by peeling off the release film. Further, according to the hydrogel sheet of the present invention, since it has good adhesiveness, it stably adheres to the skin and has an advantageous effect of excellent therapeutic effect. Furthermore, according to the hydrogel sheet of the present invention, there is an advantageous effect that no adhesive residue occurs after the treatment. [Modes for carrying out the invention] 【0020】 The hydrogel sheet of the present invention is characterized by containing a water-soluble polymer, glycerin, a crosslinking agent, and water. 【0021】 Furthermore, in a preferred embodiment of the hydrogel sheet of the present invention, the hydrogel sheet is characterized by being for conductive applications using iontophoresis, from the viewpoint of good adhesion and ease of handling. 【0022】 The water-soluble polymer is not particularly limited, but for example, gelatin, hydrolyzed gelatin, polyacrylic acid, sodium polyacrylate, partially neutralized polyacrylic acid, starch polyacrylate, polyvinyl alcohol, polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, methylcellulose, sodium carmellose, carboxyvinyl polymer, methoxyethylene maleic anhydride copolymer, N-vinylacetamide copolymer, xanthan gum, gum arabic, etc. can be used individually or in combination of two or more. From the viewpoint of excellent adhesiveness and shape retention, polyacrylic acid, partially neutralized polyacrylic acid, carboxyvinyl polymer, sodium carmellose, and hydroxypropyl cellulose are preferred, and one or a combination of two selected from sodium polyacrylate, sodium carmellose, carboxyvinyl polymer, and hydroxypropyl cellulose is particularly preferred. 【0023】 Furthermore, since polyacrylic acid or sodium polyacrylate has adhesive properties, it is considered that polyacrylic acids have the greatest influence on the adhesiveness of the formulation of the present invention. Regarding shape retention, it is thought that not only polyacrylic acids but also other water-soluble polymers such as carboxyvinyl polymer and carboxymethylcellulose sodium have an influence. In the present invention, by adjusting the amount of each component added, such as humectants such as glycerin, water, crosslinking agents, and stabilizers, the crosslinking strength, viscosity, and pH of the formulation can be optimized, and a formulation exhibiting good adhesiveness and shape retention can be obtained. 【0024】 Furthermore, in a preferred embodiment of the hydrogel sheet of the present invention, the amount of the water-soluble polymer in the hydrogel sheet is not particularly limited, but from the viewpoint of balancing adhesiveness and shape retention, it can be 3 to 30% by mass, and more preferably 5 to 25% by mass, relative to the total amount of hydrogel. If the amount is less than 3% by mass, the gel viscosity may be too low, making it difficult to form as an adhesive patch, and if it exceeds 30% by mass, the water-soluble polymer may not dissolve uniformly in the gel, and a good gel may not be formed. 【0025】 Furthermore, in a preferred embodiment of the hydrogel sheet of the present invention, the amount of water is characterized by being 30 to 85% by mass relative to the total amount of hydrogel. The amount of water in the hydrogel sheet is not particularly limited, but from the viewpoint of shape retention, adhesiveness, and conductivity, it can be 30 to 85% by mass, preferably 40 to 85% by mass, and more preferably 60 to 85% by mass relative to the total amount of hydrogel. If the water content exceeds 85% by mass, the physical properties of the gel may be destroyed and adhesive residue may occur. Also, if it is less than 30% by mass, the electrical conductivity may decrease, which may reduce the therapeutic effect. 【0026】 Furthermore, in this invention, it is not assumed that the patch will be applied multiple times, and it is possible to make it disposable, allowing for a higher moisture content in each formulation. 【0027】 While the present invention allows for multiple uses, the advantages of disposable gels are as follows. In the case of gels intended for multiple uses, if the water content is not kept low, water will evaporate during storage or application to the skin, affecting the physical properties of the formulation, such as adhesiveness. Furthermore, high water content raises hygiene concerns, such as bacterial growth. On the other hand, in the case of disposable gels of the present invention, multiple applications are not assumed, and the water content can be set to 30-85% by mass. 【0028】 Furthermore, in a preferred embodiment of the hydrogel sheet of the present invention, the amount of glycerin in the hydrogel sheet is not particularly limited, but from the viewpoint of maintaining moisturizing properties for the skin or the properties of the formulation, it can be 5 to 50% by mass of the total amount of hydrogel, and preferably 10 to 30% by mass. If the amount of glycerin in the hydrogel sheet is less than 5% by mass, the moisturizing properties for the skin will decrease, which may worsen the feeling of application. Also, if the amount of glycerin in the hydrogel sheet is more than 50% by mass, the glycerin that can no longer be maintained on the gel surface will leach out, which may cause stickiness when applied or a decrease in adhesive strength. 【0029】 Furthermore, while there are no particular limitations on the crosslinking agent in the hydrogel sheet, for example, polyvalent metal compounds such as dried aluminum hydroxide gel, aluminum glycinate, dihydroxyaluminum aminoacetate, synthetic hydrotalcite, and metal aluminometasilicate salts can be used individually or in combination of two or more. The amount to be added will vary depending on the type, but from the viewpoint of balancing adhesiveness and physical properties, 0.001 to 1% by mass relative to the total amount of hydrogel is preferred. 【0030】 Regarding the decrease in adhesive strength due to the presence of polyvalent metal ions after application to the skin, while such a phenomenon is conceivable, the effect of the decrease in adhesive strength due to the loss of moisture in the patch due to body temperature during application to the skin is more significant, and the influence of polyvalent metal ions from the skin is relatively small and can be ignored. 【0031】 Furthermore, in the present invention, there are no particular restrictions on the composition of the hydrogel sheet other than those mentioned above, and for example, excipients, humectants, stabilizers, etc., can be incorporated. 【0032】 Furthermore, in the present invention, the excipients are not particularly limited, but for example, kaolin, titanium dioxide, anhydrous silicic acid, zinc oxide, bentonite, etc., can be used alone or in combination of two or more. From the viewpoint of maintaining the physical properties of the formulation, anhydrous silicic acid is particularly preferred, and its amount is preferably 0.1 to 5% by mass relative to the total amount of hydrogel. 【0033】 Other humectants besides glycerin are not particularly limited, but are selected from the viewpoint of adjusting the viscosity of the ointment during manufacturing. For example, D-sorbitol solution, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, DL-pyrrolidone carboxylate sodium solution, etc., can be used alone or in combination of two or more, and the amount added is preferably 10 to 30% by mass relative to the total amount of hydrogel. 【0034】 As stabilizers, for example, EDTA salts, parahydroxybenzoic acid esters, tartaric acid, tocopherol acetate, ascorbic acid, sodium bisulfite, etc., can be used individually or in combination of two or more. The amount added varies depending on the type, but 0.001 to 1% by mass relative to the total amount of hydrogel is preferred. 【0035】 Furthermore, a preferred embodiment of the hydrogel sheet of the present invention is characterized by further containing an active ingredient. Examples of active ingredients include preservatives, antioxidants, plasticizers, and surfactants, and these can be incorporated into the formulation. 【0036】 Examples of preservatives include methylparaben, propylparaben, and phenoxyethanol; examples of antioxidants include tocopherol acetate, ascorbic acid, butylhydroxytoluene, and tocopherol; examples of plasticizers include fatty acid esters, crotamiton, and vegetable oils; and examples of surfactants include polyglycerin fatty acid esters, polyoxyethylene alkyl ethers, sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil, propylene glycol fatty acid esters, sorbitan monooleate, and oleyl ether. 【0037】 The hydrogel sheet of the present invention can follow the movement of the skin when applied and has sufficient adhesive strength to ensure stable electrical conductivity. Accordingly, the adhesive strength of the hydrogel sheet of the present invention is such that the ball number is 4 or higher, preferably 8 or higher, in the ball tack test method performed at an inclination angle of 30° in accordance with the ball tack test method of JIS Z0237. If the ball number is less than 4, the initial adhesive strength is low, which may cause lifting and peeling from the skin during treatment, resulting in reduced electrical conductivity and a decrease in therapeutic effect. 【0038】 As the plastic film covering the surface of the hydrogel sheet, polyethylene, polypropylene, polyester, polyvinyl chloride, or those whose surfaces have been treated with silicone, corona discharge, textured, plasma, etc., can be used. 【0039】 The method for manufacturing the hydrogel sheet of the present invention is not particularly limited and can be manufactured by known manufacturing methods. For example, a hydrogel sheet can be formed by spreading a hydrogel composed of the above-described components onto a support and covering the surface of the hydrogel with a plastic film. 【0040】 In the present invention, a support layer made of nonwoven fabric can be laminated from the viewpoint of handling the formulation. Such a hydrogel sheet has the advantage of being easy to handle because it can be stored and used simply by taking it out of the packaging bag when needed. Furthermore, as described above, in the present invention, good adhesive strength can be achieved by using polyacrylic acid or sodium polyacrylate. 【0041】 If necessary, commonly used sterilization methods such as radiation sterilization, electron beam sterilization, and ethylene oxide sterilization can be performed. 【0042】 Furthermore, the iontophoresis method of the present invention is characterized by using the hydrogel sheet of the present invention as a conductive sheet when performing iontophoresis. In other words, the inventors have discovered that when the hydrogel sheet of the present invention is used as a conductive sheet in iontophoresis methods performed in dermatology, cosmetic dermatology, and cosmetic surgery, the cosmetic effect is surprisingly enhanced. 【0043】 For example, compared to conventional alginate masks, the hydrogel sheet of the present invention has the following advantages. (1) Alginate masks require mixing with water before use, resulting in poor workability and a tendency towards inhomogeneity. However, the hydrogel sheet of the present invention does not require such mixing and is homogeneous. (2) It doesn't have the smell of an alginate mask. (3) After use, there is no sticky residue like with alginate masks. (4) It has a good feel when stuck on. (5) Excellent ODT (Oral Therapy Treatment) effect. (6) Due to the high uniformity of the product, there is no need to connect with multiple electrodes or wires, and stable current can be supplied and ion introduction can be performed by slightly overlapping it in one place. (7) Because it has adhesive properties, it can be used in areas where it is difficult to maintain the application of alginate packs, etc., and iontophoresis can be performed regardless of the area. (8) Because it can be easily cut with scissors or the like, iontophoresis can be easily performed on any part of the body, regardless of the location or shape. (9) There are virtually no problems such as the extensions getting tangled with eyelashes, etc., during the removal process, and they do not affect eyelash extensions. 【0044】 Furthermore, the iontophoresis method of the present invention is an iontophoresis method that uses the hydrogel sheet of the present invention as a conductive sheet to perform iontophoresis, characterized in that the conductive sheet has an active ingredient layer on the adhesive side. That is, in the present invention, the hydrogel sheet may contain an active ingredient. Alternatively, if it does not contain an active ingredient, an active ingredient may be applied and the hydrogel sheet of the present invention may be used to cover the active ingredient. 【0045】 In other words, the hydrogel sheet of the present invention may contain active ingredients, and in that case, ingredients that can be used as general cosmetics, such as cooling agents, fragrances, and essential oils, can be incorporated as active ingredients without any particular problem. 【0046】 For example, it contains water-insoluble components such as natural oils, including essential oils, and synthetic oils, with essential oils being an example of natural oils. Essential oils can be obtained, for example, by extraction and refining from parts of plants. 【0047】 In the present invention, the active ingredient may be applied to the skin during the actual treatment. Examples of active ingredients include substances that act on the skin, subcutaneous tissue, and the body, such as vitamin A or its derivatives, carotenoids or their derivatives, vitamin C or its derivatives, B vitamins or their derivatives, vitamin D or its derivatives, biotin, peptides, growth factors, coenzyme Q, α-riboacetic acid, flavonoids, glutathione, GPX (glutathione peroxidase), SOD (superoxide dismutase), TrX (thioredoxin), PrX (peroxiredoxin), HO-1 (heme oxygenase), catalase, quinone reductase, selenium, zinc, polyphenols, resveratrol, catechin, peeling agents (AHA, BHA), PRP, phosphatidylcholine, catalase, peroxidase, metal chloride, bilirubin, phospholipase, prptease, DNA repair enzyme, transferase, uric acid, hydrogen sulfide, and local anesthetics. For these active ingredients, for example, a gel containing vitamin A can be applied, and then a hydrogel sheet can be attached on top of it, after which electricity can be passed through it. [Examples] 【0048】 The following describes in more detail one embodiment of the present invention with reference to examples, but the present invention is not limited in any way to these examples. 【0049】 Example 1 After dissolving 1.08 g of carboxyvinyl polymer in an appropriate amount of purified water, 0.08 g of sodium edetate, 1.5 g of castor oil, 0.4 g of tartaric acid, and an appropriate amount of purified water were added in sequence and mixed. 【0050】 A dispersion containing 5.2 g of partially neutralized polyacrylic acid, 3.0 g of carboxymethylcellulose sodium, 0.06 g of dihydroxyaluminum aminoacetate, and three other components dispersed in 16.0 g of concentrated glycerin was added to this liquid and mixed uniformly to prepare a hydrogel. This hydrogel was spread between a nonwoven fabric and a plastic film to form a hydrogel sheet. 【0051】 Details of the prescription are shown in Table 1. 【0052】 [Table 1] 【0053】 Examples 2-7 Each formulation shown in Table 1 was manufactured according to the manufacturing method of Example 1 to obtain the hydrogel sheets of Examples 2 to 7. 【0054】 Example 8 After dissolving 0.48 g of carboxyvinyl polymer and 0.5 g of anhydrous silicic acid in an appropriate amount of purified water, 0.08 g of sodium edetate, 0.5 g of castor oil, 0.15 g of tartaric acid, 13.5 g of 20% polyacrylic acid aqueous solution, and an appropriate amount of purified water were sequentially added and mixed. To this solution, a dispersion of 4.6 g of partially neutralized polyacrylic acid, 3.5 g of carboxyvinyl sodium, 0.04 g of dihydroxyaluminum aminoacetate, and three other components dispersed in 14.0 g of concentrated glycerin was added and mixed uniformly to prepare a hydrogel. This hydrogel was spread between a nonwoven fabric and a plastic film to form a hydrogel sheet. 【0055】 Details of the prescription are shown in Table 1. 【0056】 [Comparative Example] An aqueous solution obtained by stirring and dispersing 30g of alginate mask (manufactured by Environ) in 120g of water was spread onto medical nonwoven gauze to a thickness of 1000g / m². 2 We obtained an alginate sheet. 【0057】 Test Example 1 The adhesiveness of the hydrogel sheets of Examples 1 to 8 and the alginate sheet of the comparative example was measured according to the following test method. The measured values were each measured three times, and the average value was obtained. The results are shown in Table 1. 【0058】 〔Adhesiveness test〕 Using the tester described in the 18th revised Japanese Pharmacopoeia Explanation Book (General Test Methods, 6.12 Adhesiveness Test Method [3.2. Inclined Ball Tack Test Method]), place the adhesive surface of the test preparation upward on a slope of 30 degrees with respect to the horizontal. Cover the upper 10 cm and lower 15 cm parts with appropriate paper, leaving a 5 cm adhesive surface in the center. 【0059】 A series of steel balls with diameters ranging from 3.2 mm to 25.4 mm were rolled from the upper end of the slope, and the number of the balls that stopped on the central adhesive surface for 5 seconds or more was measured. 【0060】 Test Example 2 The resistance values of the hydrogel sheets of Examples 1 to 8 and the alginate sheet of Comparative Example 1 were measured according to the following test method. The results are shown in Table 1. 【0061】 〔Measurement of the resistance value of each preparation〕 Using a DC voltage and current generator (VI1002 type) manufactured by Precision Gauge Co., Ltd., the resistance values of each example and the comparative example were measured from the voltage value when a current of 0.1 mV was passed at room temperature. During the measurement, the distance between the electrodes was set to 1 cm, and the measurement was repeated three times, and the average value was taken as the resistance value. 【0062】 Test Example 3 〔Human sensory test〕 A coating solution containing vitamin A was applied to the face of the subject excluding the mucous membrane. On the right side of the face, the preparation of Example 1 was pasted from above the coating solution, and on the left side of the face, an alginate mask similar to the comparative example was applied from above the coating solution. Then, an ion introduction machine IP-50K (Ito Ultrashort Wave Co., Ltd.) was used to energize at 0.8 mA, and a sensory test was conducted on the items (1) to (5) described in Table 2. <{ 【0063】 The evaluation criteria and methods for each item are shown in Table 2, and the results are shown in Table 3. The results are shown as the average score of each subject. 【0064】 [Table 2] 【0065】 [Table 3] 【0066】 Thus, in this invention, a hydrogel sheet that can be attached to a living body, particularly a hydrogel sheet used as a conductive sheet for iontophoresis, was found to be a conductive sheet that adheres stably to the skin, exhibiting excellent therapeutic effects, superior usability, no adhesive residue after treatment, and excellent handling, when a hydrogel containing a water-soluble polymer, glycerin, a crosslinking agent, and water is used, for example, as a conductive sheet in iontophoresis. [Industrial applicability] 【0067】 The hydrogel sheet of the present invention contains a water-soluble polymer, glycerin, a crosslinking agent, and water. When used as a conductive sheet in iontophoresis, it adheres stably to the skin, resulting in excellent therapeutic effects, superior usability, no adhesive residue after treatment, and excellent handling.

Claims

[Claim 1] A hydrogel sheet comprising a water-soluble polymer, glycerin, a crosslinking agent, and water, wherein the hydrogel sheet is formed between a support layer made of a nonwoven fabric and a plastic film, and the hydrogel sheet is for conductive applications by ion introduction. [Claim 2] The hydrogel sheet according to claim 1, characterized in that the plastic film is made of polyethylene, polypropylene, polyester, or polyvinyl chloride. [Claim 3] The hydrogel sheet according to claim 1 or 2, wherein the amount of the water-soluble polymer blended is 3 to 30% by mass relative to the total amount of hydrogel. [Claim 4] The hydrogel sheet according to any one of claims 1 to 3, wherein the amount of glycerin added is 5 to 50% by mass relative to the total amount of hydrogel. [Claim 5] The hydrogel sheet according to any one of claims 1 to 4, wherein the amount of the crosslinking agent is 0.001 to 1% by mass relative to the total amount of hydrogel. [Claim 6] The hydrogel sheet according to any one of claims 1 to 5, wherein the amount of water added is 30 to 85% by mass relative to the total amount of hydrogel. [Claim 7] Furthermore, the hydrogel sheet according to any one of claims 1 to 6 contains an active ingredient. [Claim 8] A conductive sheet used in an ion introduction method, wherein the conductive sheet is a hydrogel sheet according to any one of claims 1 to 7. [Claim 9] A conductive sheet used in an ion introduction method, wherein the conductive sheet is a hydrogel sheet according to any one of claims 1 to 6, and is characterized in that an active ingredient layer is provided on the adhesive side of the conductive sheet by applying an active ingredient.

Images