KR100847971B1 - A wound-healing dressing patch with hydrogel layer containing chitosan - Google Patents

Abstract

In the present invention, a hydrogel pad comprising a hydrogel consisting of a water-soluble polymer such as water-soluble chitosan, polyacrylic acid or a salt thereof, a polyol such as glycerin, a crosslinking agent, and the like, laminated on a support-adhesive polyurethane film laminated with a support, and wound In order to protect the hydrogel layer that is directly in contact with the site from external contamination, it is composed of a release film or a release paper coated structure, so it is excellent in wound healing and absorption of leaching material, and pain does not stick to the wound when detached from the wound. It relates to a chitosan hydrogel patch for wound treatment, which is scarcely present and scars hardly appear after treatment.

Water Soluble Chitosan, Hydrogel, Wound Treatment

Description

Chitosan hydrogel patch for wound healing {A wound-healing dressing patch with hydrogel layer containing chitosan}

In Figure 1 (a) and (b) is a plan view of a hydrogel patch for wound healing prepared by the present invention,

In Figure 2 (a) is a hydrogel pad, (b) is a hydrogel layer, (c) is a plan view of the hydrogel support.

In Figure 3 (a) is a transparent release film, (b) is a plan view of the release paper.

In Figure 4 (a) is a pressure-sensitive polyurethane film laminated with an S-shaped cutting support, (b) is a pressure-sensitive polyurethane film laminated with a straight cutting support, (c) is a plan view of a polyurethane film.

5 is a cross-sectional view taken along the line AA ′ of FIG. 1A.

* Explanation of symbols on the main parts of the drawings *

1: release film 2: release paper

3: hydrogel 4: hydrogel support

5: adhesive polyurethane film 6: S-shaped cutting support

7: straight cutting support 8: hydrogel pad

9: S-shaped cutting line 10: Straight cutting line

 A-A ': perforation

The present invention relates to a chitosan hydrogel patch for wound treatment, and in detail, the cutting support is laminated, and water-soluble chitosan, polyacrylic acid, or the like on a tacky polyurethane film having a function of preventing the release of water from the skin and the penetration of water from the outside. A hydrogel pad laminated with a hydrogel consisting of a salt thereof, a water-soluble polymer such as sodium carboxymethyl cellulose, a polyol such as glycerin, a crosslinking agent, and the like, is laminated to a support, and the hydrogel layer directly contacting the wound is protected from external contamination. The present invention relates to a composition of a chitosan hydrogel patch for treating a transparent or semi-transparent wound comprising a structure coated with a release film or a release paper so that it can be used. The hydrogel thus formed is a cross-linked body of three-dimensional network structure, so it creates a moisturizing environment by absorbing water-soluble chitosan and leachate, so that the wound is smoothly treated and the wound healing effect is very fast. In addition, there is almost no pain when peeling off because it does not stick to the wound, there is no residue, and there is no scab, so there is almost no scar after treatment.

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 environmental conditions such as ultraviolet rays, biochemicals, etc., and controlling the water vaporization and body temperature of the human body. However, skin damage such as burns, trauma, wounds, bedsores, etc. occur frequently in daily life, and if left undamaged skin can cause severe defects through secondary contamination, the wound must be quickly treated to remove various side effects.

On the other hand, chitosan is a folk prescription using crab shells, which has edema, anti-allergic and immunity. Crab powder (ball) is used as a cure for boils and boils. In addition, Japanese white medicine has a record of using crab and shrimp shells to treat fever, tonic, burns and skin diseases.

This chitosan is a non-toxic, biodegradable amino acid that is obtained by deacetalizing chitin in nature, such as crab, shrimp shells, squid bones, mold, mushroom mycelium, and cell walls of microorganisms. It has excellent biocompatibility, and has been known as a physiologically effective substance such as wound treatment, artificial skin, blood coagulant, immune enhancer, antibacterial and antioxidant since the 1990s.

On the other hand, chitosan, which has been used in the past, has a very strong acetylamino group intermolecular hydrogen bonds in the molecule, and it is difficult to be applied to industry because it is not dissolved in water and an organic solvent. Chitosan dissolved in water has low molecular weight chitosan or chitooligosaccharides, but chitosan has been reported to have superior efficacy at higher molecular weights. Jung BO et al ., J. Chitin Chitosan , 6 (1), 12-17 (2004)). In order to prepare such high molecular weight water-soluble chitosan, U.S. Patent No. 3,533,940 has deacetylated chitin to prepare chitosan which is dissolved in an acidic aqueous solution such as acetic acid. In case of application in patch formulations, residual acid may cause severe skin irritation. Therefore, chitosan for preparing chitosan hydrogel patch having excellent wound healing effect as the present invention should be high molecular weight, and should be easily dissolved in water.

In the composition of the hydrogel patch containing chitosan for wound treatment as an essential ingredient, water-soluble polymers such as water-soluble chitosan, polyacrylic acid or salts thereof, sodium carboxymethyl cellulose, glycerin, etc. It is made of a structure coated with a release film or a release paper so that the hydrogel pad laminated with a hydrogel composed of a polyol such as a crosslinking agent and the like is laminated on a support, and the hydrogel layer directly contacting the wound is protected from external contamination. The present invention relates to a chitosan hydrogel patch for transparent or translucent wound treatment. The hydrogel thus formed is a three-dimensional cross-linked crosslinked structure that creates a moisturizing environment by absorbing water-soluble chitosan and leachables, thereby making the wound smooth. Healed and wounded Almost no pain when the effect be very fast, do not stick to the wound away, nor leave a residue, which is characterized by scab scar does not appear after a few treatment does not occur.

Chitosan hydrogel patch designed so that the present invention is effectively attached to the wound to absorb the wound treatment and leaching has a structure as shown in FIG. Supporting the release film (1) or release paper (2), which prevents deformation of the hydrogel and prevents contamination from the outside, and a hydrogel layer (3) containing chitosan as an essential component having an absorption function of wound healing and leaching. 4) a water-resistant adhesive polyurethane film laminated to the hydrogel pad 8 and the hydrogel pad laminated to 4) to be fixed to the wound, and directly affixed to the skin (FIG. 4 (a) or (b)) )

In the present invention, the hydrogel pad is prepared by laminating the hydrogel layer 3 on the support 4.

In the present invention, the hydrogel layer (3) is composed of water-soluble polymers, plasticizers, purified water, crosslinking agents, surfactants, pH adjusting agents, chelating agents, pigments and dissolution aids, etc., in addition to the water-soluble chitosan, and exhibits the function of wound healing and leaching, The coating thickness is preferably 10 µm to 5,000 µm, more preferably 100 µm to 4,000 µm, and the most preferable coating thickness is 500 µm to 2,500 µm. If the coating thickness is less than 10㎛, the absorbing function of the leachate is weak, if the coating thickness is more than 5,000㎛ it is inconvenient to use.

In the present invention, water-soluble polymers other than water-soluble chitosan may use natural polymers, synthetic polymers and semi-synthetic polymers, and as natural polymers, collagen, gelatin, xanthan gum, carrageenan, agar, alginic acid or salts thereof, hyaluronic acid or salts thereof, pectin, Starch and the like can be used, and as the synthetic polymer, polyacrylic acid or its salt, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene oxide, methylvinyl ether maleic anhydride copolymer, isobutylene maleic anhydride copolymer, butyl methacrylate Copolymers, methoxyethylene maleic anhydride copolymers, and the like can be used, and at least one component selected from sodium carboxymethyl cellulose, soluble starch, and carboxymethyl starch can be used as the semi-synthetic polymer.

The water-soluble chitosan used the thing produced as follows as a high molecular weight chitosan represented by Structural formula (I). Chitin, a natural biopolymer, is dissolved in acetic acid, insoluble matters are removed, recrystallized with sodium hydroxide, washed with purified water, ethanol, and ether until the filtrate is neutral, and dried under reduced pressure to obtain chitosan having high deacetylation degree. . The chitosan was dissolved in acetic acid solution, decomposed into lysozyme, washed with ethanol, and ion exchanged in salt solution while sonicating to increase fluidity, and an average molecular weight of 100,000 to 300,000 daltons was prepared through a freeze-drying process. do. The chitosan thus prepared is a high molecular weight chitosan, has a weak acidity of 5.0 to 6.0 in liquidity, and is easily dissolved in water.

In the present invention, the water-soluble chitosan is preferably used 0.01 parts by weight to 10.0 parts by weight. In the range of use of water-soluble chitosan, it has excellent physical properties of mixing viscosity, and because it is uniformly chemically bonded to the three-dimensional network structure of the hydrogel after the crosslinking reaction, it does not remain on the skin even after sticking, thereby providing optimum physical properties without stickiness. Keep it. As the water-soluble polymer, polyacrylic acid or a salt thereof and sodium carboxymethyl cellulose are preferably mixed in the same ratio so as to use 1.0 part by weight to 20.0 parts by weight. More preferably, it is 5.0 weight part-15.0 weight part. When the amount is less than 1.0 part by weight, the gel strength is weak. When the amount is more than 20.0 parts by weight, the viscosity is increased when mixing the composition, making it difficult to prepare a homogeneous hydrogel.

 In the present invention, the plasticizer is 5.0 parts by weight to 50.0 parts by mixing one or two or more of glycerin, sorbitol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol, which acts as a moisturizing agent. It is preferable to use a part. In this range, the composition maintains a uniform viscosity state so that the blendability is very good, and the hydrogel maintains the optimum moisture to improve the moisturizing effect and the flexibility of the composition.

Purified water in the present invention forms a moisturizing environment in the wound with a plasticizer to prevent scabs, it is preferable to use 30.0 parts by weight to 80.0 parts by weight depending on the amount of water-soluble polymer.

In the present invention, the crosslinking agent is used in an aluminum compound, such as aluminum hydroxide, aluminum magnesium silicate, aluminum glycinate, aluminum chloride, aluminum sulfate, or a mixture of one or two or more of 0.01 parts by weight to 5.0 parts by weight. In this range of use, the crosslinking agent performs optimal crosslinking with the water-soluble polymer to prepare a hydrogel having excellent gel strength and adhesion.

In the present invention, all anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants may be used to promote transdermal absorption and maintain the stability of the compositions. You can select and use it. It is preferable to use 0.01 part by weight to 10.0 parts by weight. In general, excessive use may cause skin irritation, so it is not recommended to use more than 10.0 parts by weight.

In the present invention, the hydrogel may contain a pH adjusting agent, a chelating agent, a stabilizer, a dissolution aid, a preservative and a pigment. The pH adjusting agent may use organic acids such as citric acid, lactic acid, tartaric acid, glycolic acid, and organic bases such as monoethanolamine, diethanolamine, triethanolamine, diisopropanolamine, and the chelating agent is ethylenediaminetetraacetic acid. And salts thereof, sodium polyacrylate (molecular weight: 10,000 or less), and one or two or more kinds of phosphates can be used in combination. In addition, the stabilizer may be used antioxidants such as dibutyl hydroxy toluene, sodium pyrosulfite, butyl hydroxy anisole, ascorbic acid, the dissolution aid may be selected from animal and vegetable oils. As a preservative, it is best to use one kind or a mixture of two or more kinds of methylparaben and propylparaben, and it should not be used in excess of 0.2 parts by weight. Titanium oxide, zinc oxide, iron oxide, a water-soluble dye, a pigment, etc. are used suitably as a pigment | dye.

The composition constituting the hydrogel layer of the present invention is mint essential oil components such as menthol, camphor, wound healing medicinal ingredients, excipients, inorganic fillers and the like in addition to the above composition in the range that does not change the physical and chemical properties of the hydrogel 0.01 weight part-5.0 weight part of additives, such as a viscosity modifier, can be used, respectively.

In the present invention, the support 4 for stacking the hydrogel is a natural or chemical fiber such as nonwoven fabric, fiber, cotton, rayon or the like in a polyurethane film, polyethylene phthalate film or polyethylene film having a thickness of 10 μm to 100 μm. The mixture of species and more is characterized by laminating so that the average weight is 10 g / m 2 to 60 g / m 2.

In the present invention, a release film 1 or a release paper 2 may be used to prevent deformation of the hydrogel and prevent contamination from the outside, and the release film 1 may be transparent or white opaque polyethylene phthalate, polyethylene, Polypropylene, polyvinyl chloride, polycarbonate film is used, and the release paper (2) is a paper coated with polyethylene, and then released by silicone, fluorine and the like. It is preferable to select and use the thickness of the release film 1 or the release paper 2 in 20 micrometers-200 micrometers. Things less than 20 μm are so thin that it is difficult to maintain the shape of the hydrogel and is easily damaged. If it exceeds 200㎛ is too thick to handle is inconvenient. In particular, as shown in (a) and (b) of Figure 3 to the release film (1) or release paper (2) to express the product name, picture, logo or company name in the desired color, characterized in that it is used commercially differentiated. .

In the present invention, the hydrogel is fixed to the wound, and the adhesive polyurethane film (FIG. 4 (a) or (b)) directly affixed to the skin allows vapors emitted from the skin to pass through and does not pass moisture from outside. The adhesive polyurethane film having a function (FIG. 4C) is laminated with a support having an S-shaped or straight cut line. The S-shaped or straight-shaped cut line is provided with convenience so that the present invention can be easily removed after attaching to the wound. In addition, the pressure-sensitive adhesive used for imparting adhesion to the adhesive polyurethane film (Fig. 4 (c)) has low skin irritation and is safe for the human body, styrene-butadiene copolymer resin, styrene-isoprene-styrene copolymer, and ethylene-vinylacetate air. One kind or a mixture of two or more kinds of pressure-sensitive adhesives such as copolymer, rosin, polyisobutylene, polyacrylate copolymer, acrylate-octyl acrylamide copolymer and acrylate-vinylacetate copolymer can be used. It is preferable that the water vapor transmission rate of the adhesive polyurethane film ((c) of FIG. 4) used in the present invention is 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 100g / m² / day there is a fear that the polyurethane film adhered by sweat easily fall off, if the moisture exceeds 5,000g / m² / day is weak waterproof. In addition, as for the thickness of a polyurethane film (FIG. 4 (c)), it is good to use the thing of 10 micrometers-50 micrometers. Polyurethane (Fig. 4 (c)) in this range is soft when the skin is attached, the feeling of foreign matter is not felt, the feeling is very good when sticking. The S-shaped cutting support 6 or the straight cutting support 7 supports a thin adhesive polyurethane film, and an S-shaped cutting line or a straight cutting line is inserted to easily remove the support after affixing to the skin. The support is a film or paper made of polyethylene, polypropylene, polyethylene phthalate, polyvinyl chloride, polycarbonate, and the thickness thereof is preferably selected from the range of 20 µm to 200 µm.

Hydrogel patch for wound treatment of the present invention is prepared according to the following manufacturing method. The order of mix | blending each composition in the manufacturing method of this invention demonstrated one example, It is not limited to the manufacturing method of this invention.

Example

The step of preparing a hydrogel patch for wound treatment of the present invention is a step of preparing a hydrogel pad in a first step, the second step is to cut the hydro pad to a predetermined size S-shaped cutting support (6) or straight cutting support ( 7) the step of laminating, the third step may be divided into the step of coating the release film (1) or the release paper (2) on the hydrogel pad laminated on the S-shaped cutting support (6) or straight cutting support (7). .

Hereinafter, in the Examples and Comparative Examples of the present invention will be described in detail the step of producing a hydrogel pad, the scope of the composition in the Examples of the present invention is not limited.

Examples 1 to 5 and Comparative Examples 1 to 3

Water-soluble polymers, crosslinking agents, surfactants, preservatives, chelating agents, and antioxidants are dispersed in a plasticizer in the composition shown in Table 1, and then uniformly mixed with purified water in which the pH adjuster is dissolved and applied to the support. . Air tightly sealed and aged at 24 hours at room temperature.

Table 1. Examples 1 to 5 and Comparative Examples 1 to 3 (unit: parts by weight)

Quality evaluation method

For the compositions of Examples 1 to 5 and Comparative Examples 1 to 3, the test method and the test results for the viscosity state at the time of blending, skin residue at the time of patching, absorbency and wound healing effect are as follows.

Uniformity in blending (mixing degree)

The hydrogel composition of the present invention has a characteristic that the viscosity rises over time, and there is a limit in accurately measuring the viscosity using a viscometer, so that the uniformity during blending was observed and compared. The results are shown in Table 2.

Table 2. Uniformity in Blending

Residue Measurement

The compositions prepared in Examples 1 to 4 and Comparative Examples 1 to 3 of the present invention were cut to a size of 5 cm × 5 cm and patched to the skin of 10 subjects for 6 hours. And stickiness was analyzed on a 5-point scale, and the results are shown in Table 3.

Table 3. Residue Status

Absorbance measurement

The compositions prepared in Examples 1 to 4 and Comparative Examples 1 to 3 of the present invention were cut to a size of 5 cm × 5 cm and immersed in 25 ° C. purified water for 1 hour, then taken out and dried at room temperature for 10 minutes. The weight change is measured and calculated by the following equation. The results are shown in Table 4.

  Absorption (%) = (Weight after deposition-Weight before deposition) / Weight before deposition × 100

 Table 4. Absorbance Results (%)

Experimental Example

Wound healing effect

The wound healing effect of the present invention was evaluated for 3 weeks in the micro pigs of about 3 months of age. Using the surgical mass of Nos. 11 and 12, the skin was cut out to the back of the micro pig in the size of 2 cm × 2 cm (4 cm in length and 6 cm in width), and the control group (untreated group) ), And the compositions prepared in Example 2 and Comparative Example 2 were cut to a size of 3 cm × 3 cm and applied to each wound area three by three, and adhered to the adhesive cloth of 4 cm × 5 cm size so as not to peel off. . The compositions prepared in Example 2 and Comparative Example 2 were exchanged every three days. Wound healing effect was calculated by the following equation by measuring the change in the size of the wound, the results are shown in Table 5.

Wound Healing Effect (%) = (Initial Wound Size-Wound Size after 3 Weeks) / Initial Wound Size x 100

Table 5. Wound Healing Effects (Unit:%)

As a result of the above quality evaluation, as the content of the water-soluble polymer and the crosslinking agent increases, the viscosity becomes high, making it difficult to prepare a uniform composition, and Comparative Example 3, in which the content of the water-soluble polymer is relatively low, shows a severe phenomenon in the absorption test. Residues have been shown to remain on the skin in the presence of excess content of water-soluble chitosan that is not crosslinked. In the wound treatment effect, the control group had a scab on the wound, and the wound was dried. After the scab was removed, the wound was very rough. In Comparative Example 2, the general physical properties were excellent and the wound was smooth, but the wound healing effect was limited during the test period. In Example 2 containing water-soluble chitosan, the wound healing effect appeared relatively quickly, and it was observed that the wound area was treated very smoothly during the wound healing process. It is thought that the wound is smoothly treated because it does not produce a scab under the synergistic action and moisturizing environment of the wound treatment by water-soluble chitosan and absorbed leachate. In addition, if a scab is not generated in the wound, there is an effect that scars rarely appear after the wound treatment.

As described above, the present invention relates to a composition of a chitosan hydrogel patch for wound treatment, wherein the cutting support is laminated, and a water-soluble chitosan, poly in a tacky polyurethane film having a function of preventing moisture release and skin penetration from outside of the skin. A hydrogel pad comprising a hydrogel composed of acrylic acid or a salt thereof, a water-soluble polymer such as sodium carboxymethyl cellulose, a polyol such as glycerin, and a crosslinking agent is laminated on a support, and the hydrogel layer directly contacting the wound is removed from external contamination. To provide a technique for the composition of the chitosan hydrogel patch for transparent or semi-transparent wound treatment consisting of a structure coated with a release film to protect. In particular, the chitosan hydrogel thus prepared is a three-dimensional network cross-linking body that creates a moisturizing environment by absorbing water-soluble chitosan and leachate, so that the wound is smoothly treated, and the wound healing effect is very fast and different from the wound. There is little pain when peeling off, there is no residue, there is an advantage that can minimize the occurrence of scars after treatment.

Claims (7)

The cutting support is laminated on a hydrogel pad obtained by laminating a hydrogel containing 0.01 to 10.0 parts by weight of a water-soluble chitosan having an average molecular weight of 100,000 to 300,000 Daltons and a liquid acidity of pH 5.0 to 6.0, in the following formula (I). A chitosan hydrogel patch for wound treatment comprising a structure of a transparent or translucent phase laminated on a sticky polyurethane film and having a structure in which a hydrogel layer is coated with a release film or a release paper.

delete The hydrogel component according to claim 1, wherein the hydrogel component is water-soluble chitosan, in addition to collagen, gelatin, xanthan gum, carrageenan, agar, alginic acid or salts thereof, hyaluronic acid or salts thereof, pectin, starch, polyacrylic acid or salts thereof, polyvinyl alcohol, polyvinyl In pyrrolidone, polyethylene oxide, methylvinyl ether maleic anhydride copolymer, isobutylene maleic anhydride copolymer, butyl methacrylate acrylate copolymer, methoxyethylene maleic anhydride copolymer, sodium carboxymethyl cellulose, soluble starch and carboxymethyl starch A chitosan hydrogel patch for wound treatment containing at least one selected component and having a thickness of 10 μm to 5,000 μm. The method of claim 1, wherein the hydrogel pad is a laminate of the hydrogel on the support, the support is a polyurethane film, polyethylene phthalate film or polyethylene film in the non-woven fabric, fiber, cotton, rayon natural and chemical fibers selected from one or more A combination of two or more of them, the thickness is 10㎛ to 100㎛, chitosan hydrogel patch for wound treatment, characterized in that consisting of a structure having an average weight of 10g / ㎡ to 60g / ㎡. The cutting support according to claim 1, wherein the cutting support is a film or paper made of polyethylene, polypropylene, polyethylene phthalate, polyvinyl chloride, or polycarbonate material having an S-shaped or straight cutting line, and having a structure having a thickness of 20 μm to 200 μm. Chitosan hydrogel patch for wound treatment. The method of claim 1, wherein the adhesive polyurethane film has low skin irritation and is safe for humans, styrene-butadiene copolymer, styrene-isoprene-styrene copolymer, ethylene-vinylacetate copolymer, rosin, polyisobutylene, acrylate airborne One, or a mixture of two or more of the pressure-sensitive adhesives of the copolymer, the acrylate-octyl acrylamide copolymer and the acrylate-vinylacetate copolymer is applied, the thickness is 10 µm to 50 µm, and the water vapor transmission rate is 100 g / m² / day to Chitosan hydrogel patch for wound treatment, consisting of 5,000g / m² / one person structure. delete

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