Hydrogel patch for wounds

Abstract

The present invention relates to a hydrogel patch for a wound, and more specifically, to a transparent or translucent hydrogel patch composition for a wound characterized by a structure in which a hydrogel pad, having a hydrogel containing water-soluble chitosan laminated to a support, is laminated to an adhesive polyurethane film to which a cutting support is laminated, and the hydrogel layer is covered with a release film or release paper, wherein the support is applied by dispersing a crosslinking agent, a surfactant, a preservative, a chelating agent, and an antioxidant in a plasticizer, and then mixing it with purified water in which a pH adjuster is dissolved.

Description

Technology Field

[0001] The present invention relates to a hydrogel patch for a wound. Background Technology

[0003] The present invention relates to a hydrogel patch for a wound, and more specifically, to a composition of a transparent or translucent hydrogel patch for a wound comprising a structure in which a hydrogel composed of water-soluble chitosan, polyacrylic acid or its salt, a water-soluble polymer such as sodium carboxymethylcellulose, a polyol such as glycerin, and a crosslinking agent is laminated onto an adhesive polyurethane film having a function of blocking moisture release from the skin and moisture penetration from the outside, and the hydrogel pad is laminated onto the support, and the hydrogel layer that comes into direct contact with the wound is covered with a release film or release paper to protect it from external contamination. The hydrogel composed in this manner is a crosslinked compound with a three-dimensional mesh structure, and because it creates a moisturizing environment through the absorption function of water-soluble chitosan and exudates, the wound area is healed smoothly and the wound healing effect is very rapid. In addition, it does not adhere to the wound, so there is almost no pain when removing it, it leaves no residue, and since no scab forms, scarring is minimal after treatment.

[0004] The skin, which has the largest surface area in the human body, is an organ that plays an important role in protecting the body from harmful external environments such as ultraviolet rays and biochemical substances, as well as regulating moisture evaporation and body temperature. However, skin damage such as burns, trauma, wounds, and bedsores commonly occurs in daily life, and if damaged skin is left untreated, it can leave severe defects through secondary contamination; therefore, wounds must be treated promptly to eliminate various side effects.

[0005] Meanwhile, according to the *Donguibogam*, chitosan is a folk remedy made from crab shells that has anti-edema, anti-allergic, and immune-boosting effects. The *Compendium of Materia Medica* in China records that crab powder (meatballs) is used as a treatment for boils and sores. Additionally, there are records of the Japanese *Hakunoyaku* being used as a treatment for fever, as a tonic, and for burns and skin diseases, utilizing crab and shrimp shells.

[0006] Chitosan is a type of aminopolysaccharide obtained by deacetalizing chitin found in nature, such as in the shells of crabs and shrimp, cuttlefish bones, molds, mushroom mycelia, and the cell walls of microorganisms. It is non-toxic, biodegradable, and has excellent biocompatibility. Since the 1990s, it has been well known as a substance with physiological efficacy, such as wound healing agents, artificial skin, blood coagulants, immune enhancers, antibacterial agents, and antioxidants, as it is a substance applicable for medical use.

[0007] Meanwhile, conventional chitosan has acetylamino groups with very strong intermolecular hydrogen bonds within its molecule, so it does not dissolve in water or organic solvents, which has caused many difficulties in industrial application. While low molecular weight chitosan and chitooligosaccharides are water-soluble chitosans, it has been reported that the higher the molecular weight of chitosan, the better its efficacy (Jung BO et al., J. Chitin Chitosan, 6(1), 12~17(2004)). To produce such high molecular weight water-soluble chitosan, U.S. Patent No. 3,533,940 deacetylated chitin to produce chitosan that dissolves in acidic aqueous solutions such as acetic acid, making it commercially available; however, when applied to patch formulations for human use, such as wound healing, the residual acid can cause severe skin irritation. Therefore, the chitosan used to manufacture a chitosan hydrogel patch with excellent wound healing effects, such as the present invention, must have a high molecular weight and be easily soluble in water. The problem to be solved

[0009] The present invention relates to a transparent or translucent hydrogel patch for wounds comprising a composition of a hydrogel patch containing chitosan as an essential component for wound healing, wherein a hydrogel pad is laminated onto an adhesive polyurethane film laminated with a cutting support, wherein the hydrogel pad is formed by laminating a hydrogel composed of water-soluble chitosan, polyacrylic acid or its salt, a water-soluble polymer such as sodium carboxymethylcellulose, a polyol such as glycerin, and a crosslinking agent onto the support, and the hydrogel layer that directly contacts the wound site is covered with a release film or release paper to protect it from external contamination. The hydrogel thus composed is a crosslinked compound with a three-dimensional mesh structure that creates a moisturizing environment through the absorption function of water-soluble chitosan and exudates, thereby allowing the wound site to heal smoothly, providing a very rapid wound healing effect, causing almost no pain when peeled off as it does not adhere to the wound, leaving no residue, and preventing the formation of scabs, thus facilitating healing. It is characterized by the fact that scars rarely appear later. means of solving the problem

[0011] The present invention provides a transparent or translucent hydrogel patch composition for a wound, characterized in that the hydrogel pad, having a hydrogel containing water-soluble chitosan laminated onto a support, is laminated onto an adhesive polyurethane film to which a cutting support is laminated, and the hydrogel layer is covered with a release film or release paper, wherein the support is a transparent or translucent hydrogel patch composition characterized in that a crosslinking agent, a surfactant, a preservative, a chelating agent, and an antioxidant are dispersed in a plasticizer, and then mixed with purified water in which a pH adjuster is dissolved and applied. Effects of the invention

[0013] As described above, the present invention relates to a composition of a hydrogel patch for a wound, and provides a technology for a transparent or translucent hydrogel patch for a wound, comprising a structure in which a hydrogel composed of water-soluble chitosan, polyacrylic acid or its salt, a water-soluble polymer such as sodium carboxymethylcellulose, a polyol such as glycerin, and a crosslinking agent is laminated onto an adhesive polyurethane film having a function of blocking moisture release from the skin and moisture penetration from the outside, and a hydrogel pad is laminated onto the support, and the hydrogel layer that comes into direct contact with the wound is covered with a release film to protect it from external contamination. In particular, the chitosan hydrogel composed in this way is a crosslinked compound with a three-dimensional mesh structure that creates a moist environment through the absorption function of water-soluble chitosan and extracts, so the wound site is treated smoothly, the wound healing effect is very fast, it does not stick to the wound so there is almost no pain when peeling it off, no residue is left, and there are advantages such as minimizing scar formation after treatment. Brief explanation of the drawing

[0015] Figure 1 (a) and (b) are plan views of a hydrogel patch for wound treatment manufactured according to the present invention, and In FIG. 2, (a) is a hydrogel pad, (b) is a hydrogel layer, and (c) is a top view of a hydrogel support. In Fig. 3, (a) is a transparent release film and (b) is a plan view of a release liner. In FIG. 4, (a) is an adhesive polyurethane film laminated with an S-shaped cutting support, (b) is an adhesive polyurethane film laminated with a straight cutting support, and (c) is a plan view of the polyurethane film. Figure 5 is a cross-sectional view of the AA' cut line in Figure 1 (a). Specific details for implementing the invention

[0016] The chitosan hydrogel patch of the present invention, designed to be effectively applied to a wound for wound healing and absorption of exudates, is composed of a structure as shown in Fig. 1. It consists of a release film (1) or release paper (2) that prevents deformation of the hydrogel and prevents contamination from the outside, a hydrogel pad (8) in which a hydrogel layer (3) containing chitosan as an essential component for wound healing and exudate absorption functions is laminated onto a support (4), and a waterproof adhesive polyurethane film (Fig. 4(a) or (b)) that is laminated with a cut support to fix the hydrogel to the wound and is applied directly to the skin.

[0017] In the present invention, the hydrogel pad is manufactured by laminating a hydrogel layer (3) onto a support (4).

[0018] In the present invention, the hydrogel layer (3) is composed of a water-soluble polymer, a plasticizer, purified water, a crosslinking agent, a surfactant, a pH adjuster, a chelating agent, a pigment, and a solubilizing agent in addition to water-soluble chitosan, and exhibits wound healing and exudate absorption functions. The coating thickness is preferably 10㎛ to 5,000㎛, more preferably 100㎛ to 4,000㎛, and the most preferred coating thickness is 500㎛ to 2,500㎛. If the coating thickness is less than 10㎛, the exudate absorption function is weak, and if it exceeds 5,000㎛, the coating thickness is too thick and inconvenient to use.

[0019] In the present invention, water-soluble polymers other than water-soluble chitosan may be natural polymers, synthetic polymers, and semi-synthetic polymers. Natural polymers may include collagen, gelatin, xanthan gum, carrageenan, agar, alginic acid or its salt, hyaluronic acid or its salt, pectin, starch, etc. Synthetic polymers may include polyacrylic acid or its salt, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene oxide, methyl vinyl ether maleic anhydride copolymer, isobutylene maleic anhydride copolymer, butyl methacrylate copolymer, methoxyethylene maleic anhydride copolymer, etc. Semi-synthetic polymers may include one or more components selected from sodium carboxymethylcellulose, soluble starch, and carboxymethyl starch.

[0020] Water-soluble chitosan was used as a high molecular weight chitosan prepared as follows. Chitin, a natural biopolymer, was dissolved in acetic acid to remove insoluble components, then recrystallized with sodium hydroxide. The resulting solution was washed in the order of purified water, ethanol, and ether until the filtrate became neutral, and then dried under reduced pressure to obtain chitosan with a high degree of deacetylation. This chitosan was dissolved in an acetic acid solution to decompose it with lysozyme, washed with ethanol, and then subjected to ion exchange in a salt solution while undergoing ultrasonic treatment to increase fluidity. Chitosan with an average molecular weight of 100,000 to 300,000 daltons was then produced through a freeze-drying process. The chitosan produced in this way is a high molecular weight chitosan with a weak acidity of 5.0 to 6.0 and has the characteristic of being easily soluble in water.

[0021] In the present invention, it is preferable to use water-soluble chitosan in an amount of 0.01 to 10.0 parts by weight. Within this usage range of water-soluble chitosan, the physical properties of the mixed viscosity are excellent, and since it is uniformly chemically bonded to the three-dimensional network structure of the hydrogel after the cross-linking reaction, it does not remain on the skin after application and maintains optimal physical properties without stickiness. In addition, as a water-soluble polymer, it is preferable to use 1.0 to 20.0 parts by weight of a mixture of polyacrylic acid or its salt and sodium carboxymethylcellulose in equal proportions. More preferably, it is 5.0 to 15.0 parts by weight.

[0022] When less than 1.0 weight part is used, the gel strength is weak, and when more than 20.0 weight part is used, the viscosity increases when mixing the composition, making it difficult to manufacture a homogeneous hydrogel.

[0023] In the present invention, it is preferable to use 5.0 to 50.0 parts by weight of a mixture of one or more of the following plasticizers that act as moisturizers: glycerin, sorbitol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, ethylene glycol, and polyethylene glycol. Within this range, the compositions maintain a uniform viscosity state, resulting in excellent formulation properties, and the hydrogel maintains optimal moisture, thereby improving the moisturizing effect and the flexibility of the composition.

[0024] In the present invention, purified water plays a role in forming a moisturizing environment in the wound together with a plasticizer to prevent scabs from forming, and it is preferable to use 30.0 to 80.0 parts by weight depending on the amount of water-soluble polymer used.

[0025] In the present invention, the crosslinking agent is used in an amount of 0.01 to 5.0 parts by weight by mixing one or more types of aluminum compounds such as aluminum hydroxide, aluminum magnesium silicate, aluminum glycinate, aluminum chloride, and aluminum sulfate.

[0026] In this range of use, the crosslinking agent forms an optimal crosslink with the water-soluble polymer to produce a hydrogel with excellent gel strength and adhesiveness.

[0027] In order to promote transdermal absorption and maintain the stability of the compositions, all anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants may be used as surfactants in this invention, and one or more of these may be selected and mixed. It is preferable to use 0.01 to 10.0 parts by weight. Generally, since using an excessive amount may cause skin irritation, it is advisable not to use more than 10.0 parts by weight.

[0028] The hydrogel in the present invention may contain a pH adjuster, a chelating agent, a stabilizer, a solubilizing agent, a preservative, and a colorant. As a pH adjuster, organic acids such as citric acid, lactic acid, tartaric acid, and glycolic acid, and organic bases such as monoethanolamine, diethanolamine, triethanolamine, and diisopropanolamine may be used. As a chelating agent, one or more of ethylenediaminetetraacetic acid and its salts, sodium polyacrylate (molecular weight: 10,000 or less), and phosphates may be used in combination. Additionally, as a stabilizer, antioxidants such as dibutylhydroxytoluene, sodium pyrosulfite, butylhydroxyanisole, and ascorbic acid may be used, and animal or vegetable oils may be selected and used as a solubilizing agent. As a preservative, it is best to use one or more of methylparaben and propylparaben, and the amount used should not exceed 0.2 parts by weight. Colorants such as titanium oxide, zinc oxide, iron oxide, water-soluble dyes, and pigments are used appropriately.

[0029] The composition constituting the hydrogel layer of the present invention may, if necessary, use 0.01 to 5.0 parts by weight of each additive, such as menthol, mint-based essential oil components such as camphor, wound healing medicinal components, excipients, inorganic fillers, and viscosity modifiers, in addition to the above composition, within a range that does not alter the physicochemical properties of the hydrogel.

[0030] In the present invention, the support (4) for laminating the hydrogel is characterized by being a polyurethane film, polyethylene phthalate film, or polyethylene film with a thickness of 10 μm to 100 μm, and a mixture of one or more types of natural and chemical fibers such as nonwoven fabric, fiber, cotton, and rayon, laminated so that the average weight is 10 g / m² to 60 g / m².

[0031] In the present invention, a release film (1) or a release liner (2) may be used to prevent deformation of the hydrogel and to prevent contamination from the outside. The release film (1) is made of a transparent or white opaque film of polyethylene phthalate, polyethylene, polypropylene, polyvinyl chloride, or polycarbonate material, and the release liner (2) is made by coating paper with polyethylene and then performing a release treatment with silicone, fluorine, etc. It is preferable to select and use the thickness of the release film (1) or the release liner (2) within the range of 20㎛ to 200㎛. A thickness of less than 20㎛ is too thin, making it difficult to maintain the shape of the hydrogel and easy to damage. A thickness exceeding 200㎛ is too thick, making it inconvenient to handle. In particular, as shown in FIG. 3 (a) and (b), the product name, picture, logo, or company name is expressed in a desired color on the release film (1) or the release liner (2) to differentiate it commercially.

[0032] In the present invention, the hydrogel is fixed to the wound site, and the adhesive polyurethane film (Fig. 4 (a) or (b)) which is directly attached to the skin is laminated with a support having S-shaped or straight cutting lines on an adhesive polyurethane film (Fig. 4 (c)) which has the function of allowing vapor emitted from the skin to pass through but not allowing external moisture to pass through. The S-shaped or straight cutting lines provide convenience so that the present invention can be easily removed after being attached to the wound. In addition, the adhesive used to impart adhesiveness to the adhesive polyurethane film (Fig. 4 (c)) may be one or more types of adhesives mixed together, such as styrene-butadiene copolymer resin, styrene-isoprene-styrene copolymer, ethylene-vinyl acetate copolymer, rosin, polyisobutylene, polyacrylate copolymer, acrylate-octylacrylamide copolymer, and acrylate-vinyl acetate copolymer, which have low skin irritation and are safe for the human body. The moisture permeability of the adhesive polyurethane film (Fig. 4 (c)) used in the present invention is preferably 100 g / m² / day to 5,000 g / m² / day, and more preferably 500 g / m² / day to 2,500 g / m² / day. If the moisture permeability is less than 100 g / m² / day, there is a risk that the polyurethane film attached to the skin may easily detach due to sweat, and if it exceeds 5,000 g / m² / day, the waterproofing function becomes weak. In addition, it is preferable to use a polyurethane film (Fig. 4 (c)) with a thickness of 10 µm to 50 µm. Polyurethane in this range (Fig. 4 (c)) is soft when applied to the skin, so no foreign body sensation is felt, and the user experience is very good when attached. The S-shaped cutting support (6) or the straight cutting support (7) supports the thin adhesive polyurethane film, and an S-shaped cutting line or a straight cutting line is provided so that the support can be easily removed after being applied to the skin.This support is preferably a film or paper made of polyethylene, polypropylene, polyethylene phthalate, polyvinyl chloride, or polycarbonate, with a thickness selected from the range of 20㎛ to 200㎛.

[0033] The hydrogel patch for wound healing according to the present invention is manufactured according to the following manufacturing method. The order of mixing each composition in the manufacturing method of the present invention is described as one example and is not limited to the manufacturing method of the present invention.

[0034] Examples

[0035] The steps for manufacturing the hydrogel patch for wound treatment according to the present invention can be divided into a first step of manufacturing a hydrogel pad, a second step of cutting the hydro pad into a certain size and laminating it onto an S-shaped cutting support (6) or a straight cutting support (7), and a third step of covering the hydrogel pad laminated onto the S-shaped cutting support (6) or the straight cutting support (7) with a release film (1) or a release paper (2).

[0036] Hereinafter, the steps for manufacturing a hydrogel pad are described in detail in the embodiments and comparative examples of the present invention, but the range of composition in the embodiments of the present invention is not limited.

[0037] Examples 1 to 5 and Comparative Examples 1 to 3

[0038] A water-soluble polymer, a crosslinking agent, a surfactant, a preservative, a chelating agent, and an antioxidant are dispersed in a plasticizer according to the composition and content of the composition shown in Table 1, then uniformly mixed with purified water in which a pH adjuster is dissolved, and applied to a support. The mixture is sealed to prevent air from entering and aged by storing it at room temperature for 24 hours.

[0039]

[0040] Quality evaluation method

[0041] The test methods and test results regarding the viscosity state upon mixing, skin residue upon application, absorption rate, and wound healing effect for the compositions of Examples 1 to 5 and Comparative Examples 1 to 3 are as follows.

[0042] Uniformity (degree of mixing) during mixing

[0043] Since the hydrogel composition of the present invention has the characteristic of increasing viscosity over time, there are limitations in accurately measuring viscosity using a viscometer; therefore, the uniformity during mixing was compared by visually observing it. The results are shown in Table 2.

[0044]

[0045] Residue measurement

[0046] The compositions prepared in Examples 1 to 4 and Comparative Examples 1 to 3 of the present invention were cut into pieces measuring 5 cm × 5 cm and applied to the skin of 10 subjects for 6 hours. Afterward, the residue and stickiness were analyzed on a 5-point scale, and the results are shown in Table 3.

[0047]

[0048] Experimental Example

[0049] Wound healing effect

[0050] The wound healing effect of the present invention was evaluated for 3 weeks on micropigs aged approximately 3 months. Using surgical scalpels No. 11 and No. 12, skin was cut on the dorsal side of the micropigs to a size of 2 cm × 2 cm (with a lengthwise interval of 4 cm and a transverse interval of 6 cm). The control group (untreated group) and the compositions prepared in Example 2 and Comparative Example 2 were cut into 3 cm × 3 cm pieces and applied to each wound site in sets of three. A 4 cm × 5 cm adhesive bandage was then attached over them to prevent them from peeling off. The compositions prepared in Example 2 and Comparative Example 2 were replaced every 3 days. The wound healing effect was calculated by measuring the change in wound size with a ruler and using the following formula, and the results are shown in Table 4.

[0051] Wound healing effectiveness (%) = (Initial wound size - Wound size after 3 weeks) / Initial wound size x 100

[0052]

[0053] Based on the quality evaluation results above, as the content of water-soluble polymers and crosslinking agents increased, viscosity also increased, making it difficult to produce a uniform composition. Furthermore, Comparative Example 3, which had a relatively low content of water-soluble polymers, exhibited severe runoff during the absorption test. It was found that residue remained on the skin when the content of uncrosslinked water-soluble chitosan was excessive. Regarding wound healing effects, the control group showed scab formation on the wound, resulting in dry wound areas; after the scabs were removed, the wound area was observed to be very rough. Comparative Example 2 exhibited excellent general physical properties and a smooth wound area, but its wound healing effect was found to be limited during the test period. Example 2, containing water-soluble chitosan, showed a relatively very rapid wound healing effect, and it was significantly observed that the wound area healed very smoothly during the healing process. This is believed to be due to the synergistic effect of wound healing caused by water-soluble chitosan and the absorbed extract, as well as the smooth healing of the wound area because scabs were not formed under a moist environment. In addition, if a scab does not form on the wound site, it has the effect of minimizing scarring after treatment. Explanation of the symbols

[0055] 1: Release film 2: Release paper 3: Hydrogel 4: Hydrogel support 5: Adhesive polyurethane film 6: S-shaped cut support 7: Straight cutting support 8: Hydrogel pad 9: S-shaped cut line 10: Straight cut line A-A': Dotted line

Claims

Claim 1 A transparent or translucent hydrogel patch composition for a wound, characterized in that the hydrogel pad, having a hydrogel containing water-soluble chitosan laminated onto a support, is laminated onto an adhesive polyurethane film to which a cutting support is laminated, and the hydrogel layer is covered with a release film or release paper, wherein the support is characterized by dispersing a crosslinking agent, a surfactant, a preservative, a chelating agent, and an antioxidant in a plasticizer, and then mixing and applying the mixture with purified water in which a pH adjuster is dissolved. Claim 2 A hydrogel patch composition for a wound according to claim 1, characterized in that it contains 0.01 to 10.0 parts by weight of water-soluble chitosan having an average molecular weight of 100,000 to 300,000 daltons and being weakly acidic with a pH of 5.0 to 6.0, and has a thickness of 10㎛ to 5,000㎛. Claim 3 A hydrogel patch composition for a wound according to claim 1, characterized by containing one or more components selected from collagen, gelatin, xanthan gum, carrageenan, agar, alginic acid or its salt, hyaluronic acid or its salt, pectin, starch, polyacrylic acid or its salt, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene oxide, methyl vinyl ether maleic anhydride copolymer, isobutylene maleic anhydride copolymer, butyl methacrylate copolymer, methoxyethylene maleic anhydride copolymer, sodium carboxymethylcellulose, soluble starch, and carboxymethyl starch as hydrogel components other than water-soluble chitosan.

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