KR100333317B1 - Method for preparation of hydrogels dressings by using radiation - Google Patents

Abstract

The present invention relates to a method for preparing hydrogel dressing using radiation, and specifically, a method of preparing an aqueous solution by mixing polyvinylpyrrolidone synthetic polymer with chitosan, chitosan and polyethylene oxide, or sodium alginate and polyethylene oxide ( Step 1); Molding the aqueous solution of step 1 into a sheet form (step 2); Packing the sheet of step 2 (step 3); And it relates to a method for producing a hydrogel dressing comprising the step (step 4) of irradiating the packaged sheet of step 3, the hydrogel dressing according to the present invention is particularly for the treatment of wounds such as adhesiveness, gel strength, etc. It is suitable and the wound healing effect is improved.

Description

Method for preparation of hydrogels dressings by using radiation

The present invention relates to a method for preparing hydrogel dressing using radiation, and specifically, a method of preparing an aqueous solution by mixing polyvinylpyrrolidone synthetic polymer with chitosan, chitosan and polyethylene oxide, or sodium alginate and polyethylene oxide ( Step 1); Molding the aqueous solution of step 1 into a sheet form (step 2); Packing the sheet of step 2 (step 3); And irradiating the packaged sheet of step 3 to radiation (step 4).

To treat severe burns, autologous transplantation or in vitro culture tissue of the patient's fibroblasts is finally implanted. Usually, a significant amount of time elapses after the injury and before such a procedure should be used to effectively prevent infection of the affected area. Therefore, the dressing for burn treatment should absorb body fluids such as exudate and keep moisture on the wound for a long time, prevent infection of the wound from bacteria, and be easy to attach and detach to the wound or skin. . In addition, it must be transparent to be able to visually check the progress of the wound treatment, have good oxygen permeability, be easy to handle and store, and be able to control and sterilize the drug.

One of the materials capable of satisfying the above conditions is a polymer hydrogel. Polymeric hydrogels are generally prepared using synthetic polymers such as polyvinylpyrrolidone, polyhydroxyethyl methacrylate, polyvinyl alcohol, and natural polymers such as gelatin, agar and collagen.

Hydrogel is a material that is temporarily used for burn regeneration or skin regeneration that requires continuous wet condition.It usually contains more than 90% water and promotes healing. Hydrogels are also used for contact lenses, cartilage, etc., in addition to wound dressing because they have affinity with blood, body fluids, and biological tissues.

Polymer materials that can contain water usually have a three-dimensional network structure, and mainly include carboxyl groups (COOH), carboxamide groups (CONH ₂ ), carboximide groups (CONH), and sulfonic acid groups (SO ₃ H). It has a hydrophilic functional group and contains moisture by capillary action and osmotic pressure. Although hydrogels contain large amounts of water and are not soluble in water, they are also due to some electrostatic and lipophilic interactions, but usually due to the covalent bond structure between the polymer chains.

On the other hand, as a method of preparing a polymer hydrogel, there are a chemical method and a method using radiation. In the case of the chemical method, the polymer is crosslinked using a crosslinking agent. For example, the polyvinyl alcohol aqueous solution, which is a synthetic polymer, may be crosslinked by formaldehyde, gurutalaldehyde, or the like, and may be repeatedly frozen and thawed to form a gel. However, crosslinking by aldehydes is not completely removed and toxicity by aldehydes remains a problem, and gels formed by repetition of freezing and thawing have a problem of not having high strength.

In order to prepare hydrogel by chemical crosslinking method using polyvinylpyrrolidone, polyvinylpyrrolidone is dissolved in distilled water, followed by ethylene glycol dimethacrylate, propylene glycol dimethacrylate, and tetraethylene glycol dimethacryl. Polyfunctional monomers, such as a rate or a trimetholpropane triacrylate, are added and heated together with a chemical initiator. However, in the chemical crosslinking method, when the reaction is completed, the unreacted initiator and monomer should be removed by washing. If the washing is insufficient, an unreacted initiator or a crosslinking agent may be present in the hydrogel. As mentioned above, these substances are highly toxic and can cause serious problems when used as biomaterials.

Therefore, a method of preparing a polymer hydrogel using radiation instead of the chemical crosslinking method as described above has been developed.

In the method of preparing hydrogel using radiation, since no harmful chemical crosslinking agent or initiator is used, there is no need to remove residual crosslinking agent or initiator after crosslinking, and it is capable of simultaneously sterilizing with crosslinking. In addition, there is no need to apply heat in the cross-linking process, it is possible to cross-link even in a cooled state, and by adjusting only the radiation dose, there is a feature that can freely control the physical properties of the hydrogel without changing the composition.

U.S. Patent No. 5,389,376 describes a method of synthesizing a tacky hydrogel because it crosslinks a polyvinylpyrrolidone and glycerin aqueous solution by irradiation. In addition, US Pat. No. 5,480,717 describes a method of preparing a composite by fixing a hydrogel on a support, using polyvinylpyrrolidone as a polymer.

As described in the above patents, the polyvinylpyrrolidone hydrogel of the polymer hydrogel is particularly excellent as a dressing for wound treatment because of its non-toxicity and good physical properties. However, the conventional polyvinylpyrrolidone hydrogel has a disadvantage that the adhesion is higher than necessary, so that when the polyvinylpyrrolidone hydrogel dressing is removed from the wound after the wound treatment, part of the polyvinylpyrrolidone remains in the wound. This can adversely affect burns, such as burns. In addition, since the hydrogel basically absorbs water and is dried while maintaining mechanical properties and shape, it is necessary to appropriately adjust the gel strength and swelling property.

Accordingly, the present inventors endeavored to prepare a hydrogel dressing for wound treatment with better properties, and thus, after preparing an aqueous solution by mixing chitosan, chitosan and polyethylene oxide, or sodium alginate and polyethylene oxide in a polyvinylpyrrolidone synthetic polymer, The present invention was completed by finding out that a hydrogel dressing having excellent gel strength, swelling property, adhesiveness, and sterilization ability can be prepared.

It is an object of the present invention to provide a method for producing a hydrogel dressing for wound treatment and a hydrogel dressing prepared by the method.

1 is a schematic diagram of a rotating device used for irradiation;

2 is a graph showing the relationship between the polymer content and the gel strength,

3 is a graph showing the relationship between the radiation dose and the gel strength,

4 is a schematic diagram of an apparatus for measuring water evaporation of hydrogel;

5 is a graph showing the change in water evaporation amount of the hydrogel with respect to time,

6 is a graph showing the change in gel strength of hydrogel with respect to time,

7 is a graph showing the swelling degree change of the hydrogel with respect to time,

8 is a graph showing the change in gel strength of a hydrogel versus time (swelling degree).

In order to achieve the above object, in the present invention

1) preparing an aqueous solution by mixing a polyvinylpyrrolidone synthetic polymer with chitosan, chitosan and polyethylene oxide, or sodium alginate and polyethylene oxide (step 1);

2) molding the aqueous solution of step 1 into a sheet form (step 2);

3) packing the sheet of step 2 (step 3); And

4) It provides a method for producing a hydrogel dressing consisting of a step (step 4) of irradiating radiation to the packaged sheet of step 3.

Hereinafter, the present invention will be described in detail.

Hydrogels (or hydrogel dressings) for wound treatment such as burns using polymers have many functional advantages even if they are not satisfactory in mechanical properties. To overcome this problem, it is necessary to select a polymer having an appropriate radiation dose, an appropriate polymer, and an appropriate molecular weight. In the case of high molecular weight polymers, if they are mixed with each other and there is no special interaction between components, they may be incompatible or very small, resulting in phase separation, resulting in lower final properties.

Therefore, in the present invention, the appropriate polymer material and the appropriate radiation dose were determined in consideration of these factors.

Polyvinylpyrrolidone has been used as a plasma because it has been found to be biocompatible as a water-soluble polymer, and recently, research has been actively conducted as a vitreous substitute for the eye, and has been widely used as a biomaterial for several decades. . Since the polymer has oxygen and nitrogen in the unit structure to form hydrogen bonds with water molecules, it can contain a lot of water in the network structure, which is suitable for making a hydrogel.

In particular, the molecular weight of the polyvinylpyrrolidone synthetic polymer is preferably 200,000 to 1,300,000. When the molecular weight is 200,000 or less, especially 40,000 or less, the viscosity of the polymer solution is very low, so that it is easy to prepare an aqueous solution, but has mechanical properties unsuitable for use as a hydrogel for dressing. Polyvinylpyrrolidone having a molecular weight of 1.3 million or more is not commercially available.

In US Pat. No. 5,480,717, polyvinylpyrrolidone has the best physical properties when the molecular weight is in the range of 200,000 to 400,000, and when the molecular weight is higher than that, it is difficult to make a high concentration of aqueous solution and the physical properties decrease again. Also in the present invention, when the molecular weight is 40,000 or less, the gelation rate is low and the gel strength is low, and thus it is not suitable for use as a hydrogel for wound treatment. However, according to the results of the present inventors' experiment, it was possible to obtain an aqueous solution having a higher molecular weight than that mentioned in the US patent, for example, about 1.3 million or 20%, and to prepare a hydrogel having good physical properties. In addition, although the epidermal layer was prepared on the surface to prevent the hydrogel from cracking due to evaporation of water, the hydrogel prepared by the present invention did not break the hydrogel due to evaporation of water even after 14 days and the strength of the gel did not decrease. It contained a large amount of water and did not require the addition of a secondary epidermal layer.

In step 1, the polyvinylpyrrolidone synthetic polymer is preferably contained in an aqueous solution of 3 to 25% by weight. When the hydrogel is made of an aqueous polymer solution of 3% by weight or less, a gel strength that can be used as a dressing cannot be obtained, and the viscosity of the aqueous polymer solution is too large to make a solution at 25% by weight or more.

On the other hand, polyvinylpyrrolidone is not toxic and has good physical properties and has excellent properties as a dressing for wound treatment, but it has higher adhesiveness than necessary so that the polyvinylpyrrolidone hydrogel dressing is removed from the wound after wound treatment. The disadvantage is that some of the vinylpyrrolidone remains. Animal experiments in mice showed that polyvinylpyrrolidone hydrogels tend to stick too tightly to wounds, published by Yoshii et al. (Radiation Physics and Chemistry, 55, 1999, 133-138). It has been described that some dressing materials stick to wounds because of the low strength of polyvinylpyrrolidone hydrogels. However, even if the strength of the material is large, if there is a chemical interaction between the material and the protein, the material may stick well to the wound, so in the preferred embodiment of the present invention, polyethylene oxide, which is known to have low protein adsorption and cell adhesion, is known. To prepare a hydrogel by mixing.

Polyethylene oxide, like polyvinylpyrrolidone, is one of the materials that are attracting attention as a medical polymer. One of the biggest problems when making materials that come into contact with blood is the phenomenon of thrombus, which is usually due to protein adsorption and platelet adsorption, resulting in blood clots. However, since polyethylene oxide has a very small surface free energy at the interface with water, it exhibits antithrombogenicity, and therefore, it is preferable to use polyethylene oxide or a derivative thereof when used as a material in which contact with blood is inevitable.

In step 1, the polyethylene oxide is preferably contained in an aqueous solution of 0.2 to 5% by weight. The addition of polyethylene oxide improves the flexibility of some hydrogels. The use of 0.2 wt% or less of aqueous solution is not very effective and the addition of 5 wt% or more of aqueous solution reduces the force at break.

Chitosan is a generic term for deacetylation of chitin, which is contained in shellfish such as crabs and shrimps, crickets and insects such as grasshoppers, and mollusks such as squids, and in cell walls of higher plants such as strains and birds. Next to cellulose is abundant natural polymers. Chitin or chitosan exhibits functions such as biocompatibility, antimicrobial, biodegradability, etc., and is generally known to be more effective in chitosan than chitin. In addition, chitosan not only inhibits the development of bacteria and fungi, but also exhibits hemostatic properties, making it suitable for ound dressings.

The hydrogel dressing according to the manufacturing method of the present invention may include chitosan, and in step 1, it is preferable to include chitosan in an aqueous solution of 0.1 to 10% by weight. If the amount is less than 0.1% by weight, the effect of chitosan is weak, and more than 10% by weight of chitosan is difficult to dissolve in the low concentration acid solution.

Since chitosan has a disadvantage of being insoluble in water, it is preferable to dissolve chitosan in 0.1-3 M acetic acid solution in step 1 and then mix it with an aqueous polyvinylpyrrolidone solution or a mixed aqueous solution of polyvinylpyrrolidone and polyethylene oxide. desirable.

On the other hand, chitosan alone can be used in admixture with a polyvinylpyrrolidone solution, but it is more effective to add polyethylene oxide to reduce adhesiveness. By adding polyethylene oxide, not only the flexible molecular structure of polyethylene oxide can supplement the rigid properties of chitosan, but also the compatibility of the hydroxyl group or the amine group of chitosan with polyethylene oxide is excellent in compatibility. The results of animal experiments in rats of polyvinylpyrrolidone-chitosan hydrogel prepared by mixing chitosan solution with polyvinylpyrrolidone solution showed good wound healing effect, but the hydrogel dressing was affected by the adhesive effect of polyvinylpyrrolidone at the end of treatment. Since sticking to the wound appeared, it is more preferable to prepare hydrogel by adding polyethylene oxide in addition to chitosan.

Algin is obtained from algae, from which the water-insoluble alginic acid and the water-soluble salt sodium alginate and the water-insoluble salt calcium alginate can be obtained. In general, ion exchange of sodium and calcium ions in wound fluids allows more absorption of wound exudates, and algin compounds such as sodium alginate have been reported to be hemostatic.

The hydrogel dressing prepared by the method of the present invention may include sodium alginate, and sodium alginate in step 1 is preferably included in an aqueous solution of 0.2 to 5% by weight. If it is 0.2 wt% or less, the effect of sodium alginate is less, and if it is 5 wt% or more, the viscosity of the solution is large, making it difficult to prepare an aqueous solution, and gel strength is very low even when a gel is prepared.

The hydrogel added with sodium alginate can be seen that the water swelling degree is greatly increased once. Therefore, even in the case of the hydrogel to which chitosan is added, it is more preferable to add sodium alginate.

On the other hand, when the polyvinylpyrrolidone synthetic polymer is mixed with chitosan and polyethylene oxide in the preparation of the hydrogel dressing, the sheet of step 2 is first irradiated with 10-20 kGy of radiation to gel and the formed gel is 0.1-1 M. It is preferable to induce the immobilization and neutralization of chitosan in an aqueous sodium hydroxide solution, wash and package with distilled water, and irradiate the secondary radiation of step 4 to about 25 kGy.

Step 3 is a step of packaging the hydrogel prepared in the form of a sheet in step 2 may be used a conventional packaging material, for example, may be used a polymer film such as polyethylene.

In the step 4, conventional gamma rays (γ-rays) or electron beams (β-rays) may be used. Irradiation in step 4 may crosslink the polymer and sterilize the hydrogel.

In this case, the radiation dose is preferably 20 to 100 kGy. Since the minimum dose required for sterilization is known to be about 25 kGy, the radiation dose should be at least 20 kGy so that crosslinking and sterilization can be performed simultaneously. On the other hand, if the radiation dose is 100 kGy or more, the absorption rate or gel strength is rather reduced.

In another aspect, the present invention provides a hydrogel dressing prepared by the above production method.

Although hydrogel having a three-dimensional network structure has advantages similar to those of living tissues and excellent compatibility with living tissues, it has been reported that the mechanical strength decreases rapidly after swelling. However, the hydrogel prepared by the method of the present invention does not significantly decrease the mechanical properties with increasing swelling over time. In addition, the gel strength tends to increase rapidly over time due to the evaporation of moisture, and the gel strength is almost constant at low concentrations of the polymer.

In addition, the hydrogel dressing according to the present invention has basic properties for use in treating wounds such as burns, that is, absorption of body fluids, prevention of infection from bacteria, ease of attachment to wounds and skin, transparency, ease of handling, storage and sterilization properties. Have

In particular, the hydrogel dressing according to the present invention has a suitable adhesiveness for treating wounds such as burns by adding a small amount of polyethylene oxide to polyvinylpyrrolidone and performing radiation crosslinking treatment, and chitosan or sodium alginate having a wound healing function is added thereto. The addition improved physical properties as well as wound healing.

Hereinafter, the present invention will be described in more detail with reference to Examples.

However, the following examples are illustrative of the present invention, and the content of the present invention is not limited by the examples.

Example 1 Preparation of Hydrogel Dressing 1

1 g of polyethylene oxide (molecular weight 200,000, sigma) and 19 g of polyvinylpyrrolidone (molecular weight 1.3 million) were dissolved in 80 g of distilled water. Each was poured 4 mm high into a Petri dish mold and placed in a clean room for 24 hours to remove bubbles. Thereafter, a polyethylene bag was sealed and the cobalt-60 gamma rays were irradiated at 25 kGy to obtain a polyvinylpyrrolidone-polyethylene oxide hydrogel. At this time, in order to ensure that a constant dose is delivered to each point of the solution contained in the petri dish mold, the petri dish containing the polymer solution is placed on the rotating plate having a petri dish size groove and the solution is kept constant. To be investigated.

The hydrogel prepared above was taken out of the bag, soaked in distilled water for 48 hours, and then wiped off the water on the surface with cellulose paper. Then, the weight (W _s ) was measured. After the hydrogel was placed in a vacuum oven dried at 60 ℃ 48 hours to measure the weight (W _d). Gel content and swelling degree of the hydrogel were calculated by Equations 1 and 2, respectively.

The gelation rate of the prepared hydrogel was 68.5%, and the degree of swelling was 1550%.

Example 2 Preparation of Hydrogel Dressing 2

1 g of polyethylene oxide (molecular weight 200,000, sigma) and 18 g of polyvinylpyrrolidone (molecular weight 1.3 million) were dissolved in 80 g of distilled water, and 1 g of sodium alginate was added to the mixed solution to dissolve it. Thereafter, cobalt-60 gamma rays were irradiated at 25 kGy in the same manner as in Example 1 to prepare polyvinylpyrrolidone-polyethylene oxide-sodium alginate hydrogel.

The gelation rate and swelling degree of the prepared hydrogel were measured in the same manner as in Example 1, and the gelation rate of the prepared hydrogel was 69.0% and the swelling degree was 3200%.

Example 3 Preparation of Hydrogel Dressing 3

0.5 g of polyethylene oxide (molecular weight 200,000, sigma) and 9.5 g of polyvinylpyrrolidone (molecular weight 1.3 million) were dissolved in 90 g of distilled water. Separately, since chitosan is insoluble in water, 1 g of chitosan (TCI) was dissolved in 99 g of 1 M acetic acid solution to prepare a chitosan solution. The mixed solution and the chitosan solution were mixed at a weight ratio of 2: 1 to prepare a polyvinylpyrrolidone-polyethylene oxide-chitosan mixed solution. Thereafter, molding was carried out in the same manner as in Example 1, and cobalt-60 gamma rays were irradiated at a 10 kGy dose.

After the first irradiation, the hydrogel was taken out, soaked in 1 M sodium hydroxide solution for 30 minutes, shaken, immobilized and neutralized, washed with distilled water, sealed with polyethylene bag, and irradiated with 25 kGy again in the same manner as in Example 1 Pyrrolidone-polyethylene oxide-chitosan hydrogel was obtained.

The gelation rate and swelling degree of the prepared hydrogel were measured in the same manner as in Example 1, and the gelation rate of the prepared hydrogel was 65% and the swelling degree was 2300%.

The results of Examples 1 to 3 are summarized in Table 1 below.

Gelation rate and swelling degree of hydrogel Hydrogel % By weight Irradiation dose (kGy) Gelation rate (%) Swelling degree (%) Polyvinylpyrrolidone Polyethylene oxide Sodium alginate Chitosan Example 1 19 One - - 25 68.5 1550 Example 2 18 One One - 25 69.0 3200 Example 3 6.33 0.33 - 0.33 35 65 2300

As can be seen in Table 1, the hydrogels prepared in Examples 1 to 3 all exhibited a suitable gelling rate or swelling degree of physical properties for use as a dressing for dressing, and especially when sodium alginate was added, the swelling degree increased.

Example 4 Preparation of Hydrogel Dressing According to Chitosan Content Change

Hydrogel was prepared by varying the content of polyvinylpyrrolidone and chitosan.

20 g of polyvinylpyrrolidone (molecular weight 360,000, sigma) was dissolved in 80 g of distilled water to prepare a polyvinylpyrrolidone solution. Separately, 1 g of chitosan (TCI) was dissolved in 99 g of 1 M acetic acid solution to prepare a chitosan solution. The polyvinylpyrrolidone solution and the chitosan solution were mixed in a weight ratio of 4: 1, 2: 1, 1: 1, 1: 2, and 1: 4, respectively. Each solution was poured 4 mm high into a Petri dish mold and placed in a clean room for 24 hours to remove bubbles. This was first irradiated with cobalt-60 gamma ray at 20 kGy, and then immobilized and neutralized by shaking for 30 minutes in 1 M aqueous sodium hydroxide solution, and washed with distilled water. Finally, after packaging this with a polyethylene film, the cobalt-60 gamma ray was irradiated with 30 kGy to prepare polypyrrolidone-chitosan hydrogel having various compositions. When irradiating, the same rotary apparatus as in Example 1 was used, and the gelation rate and swelling degree were measured in the same manner as in Example 1, and the results are shown in Table 2 below.

Gelation rate and swelling degree of polyvinylpyrrolidone-chitosan hydrogel Hydrating Gel 20% by weight solution of polyvinylpyrrolidone: 1% by weight solution of chitosan (weight ratio) % By weight Irradiation dose (kGy) Gelation rate (%) Swelling degree (%) Polyvinylpyrrolidone (wt%) Chitosan (% by weight) Polyvinylpyrrolidone (molecular weight 360,000) -chitosan 4: 1 16 0.2 50 75 700 2: 1 13.3 0.33 50 77 590 1: 1 10 0.5 50 73 920 1: 2 6.7 0.67 50 74 1140 1: 4 4 0.8 50 69 1950

In the case of the polyvinylpyrrolidone-chitosan hydrogel, the weight ratio of the solid content in the aqueous solution did not significantly affect the gelation rate but the swelling degree. That is, as the weight of the solid content increases, the density of the three-dimensional network increases, indicating a decrease in swelling degree.

Example 5 Preparation of Hydrogel Dressing According to Polymer Content Change

One of the factors to be considered important in using a hydrogel as a dressing is strength, and a hydrogel was prepared according to a change in polymer content to measure the change in strength.

Mixed solution so that the concentration of these polymers in distilled water is 5, 10, 15 and 20% by weight while maintaining the weight ratio of polyethylene oxide (molecular weight 200,000) and polyvinylpyrrolidone (molecular weight 1.3 million) at 1:19. Was prepared. After gelation in the same manner as in Example 1 and then packaged and irradiated with cobalt-60 gamma rays 30 kGy to prepare a hydrogel.

The prepared hydrogel was unpacked, 3.5 mm thick, 20 cm ² wide specimens were prepared and measured for strength using a texture analyzer (Texture-Analyzer), the strength is shown in Figure 2 calculated by the following equation (3).

As can be seen in Figure 2, gel strength was directly proportional to the concentration of polyvinylpyrrolidone.

Example 6 Preparation of Hydrogel Dressing According to Irradiation Dose

1 g of polyethylene oxide (molecular weight 200,000, sigma) and 19 g of polyvinylpyrrolidone (molecular weight 1.3 million) were dissolved in 80 g of distilled water. Each was poured 4 mm high into a Petri dish mold and placed in a clean room for 24 hours to remove bubbles. Then, the polyvinylpyrrolidone-polyethylene oxide hydrogel was prepared by sealing with a polyethylene bag to irradiate gamma rays at 25, 30, 40, and 50 kGy doses, respectively. At this time, each point of the solution was irradiated using the same rotary device as in Example 1 so that the same dose was irradiated. Gel strength was measured in the same manner as in Example 5, the results are shown in FIG.

As can be seen in Figure 3, the gel strength increased as the radiation dose decreased.

<Experimental Example 1> Water evaporation amount of the hydrogel with time

Hydrogels suitable for wound dressings should be applied to the affected area to maintain adequate moisture for the duration of use. Therefore, the following experiment was conducted to find out the water evaporation amount of the hydrogel according to the present invention.

In the present experimental example, the change in moisture evaporation amount of the hydrogel was measured using the apparatus as shown in FIG. 4. First, a net was installed in a water bath in which the water temperature was maintained at 37 ° C., and a sample was placed thereon. At this time, the humidity around the sample placed on the net was 60 to 80%. That is, the water vapor at 37 ° C. was allowed to come into contact with the lower surface of the hydrogel on the mesh and the other side of the hydrogel was in air rather than water vapor.

The weight of evaporated water (water evaporation amount, ΔW) was calculated by the following equation.

Experimental results for each of the hydrogels prepared in Examples 1 to 3 are shown in FIG. 5.

As can be seen in Figure 5, the evaporation rate of water was slightly faster than the polyvinylpyrrolidone-polyethylene oxide hydrogel of Example 1 than the polyvinylpyrrolidone-polyethylene oxide-sodium alginate hydrogel of Example 2. However, as a whole, the hydrogels of Examples 1 to 3 exhibited an evaporation rate of about 0.1 g / cm ² for 6 hours, resulting in very small moisture evaporation rate with time. Therefore, it was confirmed that the hydrogel according to the present invention is suitable as a wound dressing material.

Experimental Example 2 Strength Change of Hydrogel with Time

In Experimental Example 1, while the moisture of the hydrogel was evaporated, the strength of the hydrogel changed with time was measured. Gel strength was measured in the same manner as in Example 5, the results are shown in FIG.

As can be seen in Figure 6, both the polyvinylpyrrolidone-polyethylene oxide hydrogel of Example 1 and the polyvinylpyrrolidone-polyethylene oxide-sodium alginate hydrogel of Example 2 increased in strength over time. In particular, the strength of the polyvinylpyrrolidone-polyethylene oxide hydrogel initially increased slightly, and then rapidly increased after 4 hours, and the rate of increase of the strength was faster than that of the polyvinylpyrrolidone-polyethylene oxide-sodium alginate hydrogel. On the other hand, in the polyvinylpyrrolidone-polyethylene oxide-chitosan hydrogel of Example 3, no change in strength was observed with time, which is considered to be due to the low concentration of the polymer.

Experimental Example 3 Variation of Swelling Degree of Hydrogel with Time

After immersing the hydrogel prepared in Examples 1 to 2 in water at a temperature of 37 ℃ was observed the degree of swelling changes with time. Swelling degree was calculated by the above equation (2), the results are shown in FIG.

The water content of the two hydrogels obtained immediately after gamma irradiation was slightly larger than that of Example 2 containing sodium alginate, but the difference was insignificant. But as time went on, the difference increased significantly. That is, as shown in Figure 7, the hydrogel containing sodium alginate was faster than the initial swelling rate, the degree of swelling or maximum swelling during the swelling was relatively much larger.

On the other hand, both hydrogels continued to swell and showed an inflection point that reached equilibrium after about 14 hours, and reached equilibrium after about 23 hours.

Experimental Example 4 Intensity Change of Hydrogel Over Time

With respect to the hydrogels prepared in Experimental Examples 1 to 2, the strength of the hydrogels changed while swelling under the same experimental conditions as in Experimental Example 3 was measured. Gel strength was calculated by the above Equation 3, the results are shown in FIG.

The initial strength of the polyvinylpyrrolidone-polyvinyl oxide hydrogel of Example 1 was about twice as large as that of the polyvinylpyrrolidone-polyethylene oxide-sodium alginate hydrogel of Example 2, and the strength at the maximum swelling was relatively high. 4-5 times larger.

On the other hand, the gel strength of the hydrogel decreased gradually as it swelled. However, the hydrogel of Example 1 had an equilibrium value of about 100 g · cm, and the hydrogel of Example 2 had an equilibrium value of about 20 g · cm, and both hydrogels had a strength that could be handled even after swelling reached an equilibrium state. It was found to have.

Experimental Example 5 Effect of Hydrating Gel on Bacteria Penetration

Dressings for the treatment of burns or wounds should be able to absorb exudate and prevent infection from external bacteria. Therefore, the following experiment was to examine the effect of blocking the bacterial penetration of the hydrogel according to the present invention.

A hydrogel dressing having a thickness of 3 mm prepared in Examples 1 to 3 was used in the experiment, completely separated from the top surface of the dressing, and the hydrogel to keep moisture. The inoculation of the cultured bacteria on the upper surface of the dressing was examined to see if the bacteria migrated to the lower surface to determine the effect of blocking the bacterial penetration of the hydrogel dressing.

First, E. coli , S. aureus , and P. putida were taken once with sterile platinum, and then 100 ml of the prepared culture solution [3 g of bee extract, peptone ) 5 g, agar (15 g, agar, 1,000 ml of distilled water), and the strain was prepared by incubating for 20 hours in a 37 ℃ incubator. 9 ml of the culture solution and 1 ml of the strain solution were diluted in a test tube, and then 1 ml of the solution was inoculated on the upper surfaces of the hydrogels of Examples 1 to 3, respectively. After 5 days, the lower surface of the hydrogel was directly observed under a microscope to determine the presence of bacteria.

As a result of the experiment, all of the hydrogels of Examples 1 to 3 had no bacteria used in the experiment at the bottom surface thereof, and it was found that the hydrogel dressing according to the present invention had an excellent effect of blocking bacterial penetration.

Experimental Example 6 Wound Healing Effect of Hydrogel

The epidermis was removed in two rounds of 1.3-cm diameter each from the back of the experimental white rat of about 150-200g and wounded. On one wound, the hydrogels of Examples 1 and 2, each having a thickness of 3 mm and a size of 1.5 × 1.5 cm, were attached to the white rats belonging to each group, and on the other wound, 1.5 × 1.5 cm commercial vaseline gauze. Attached. On top of this, each 2 × 2 cm Tegaderm (3M company) and suture were fixed to the wound, and the treatment progress was observed. The hydrogel and vaseline gauze were changed every three days. The experimental results are shown in Table 3 below.

Hydrogel composition Healing period Healing state Characteristic Example PVP / PEO ^a 10-11 days Good Excellent Healing Power Example PVP / PEO / AL ^b 10-11 days Good Excellent Healing Power Example PVP / CH ^c 9-10 days Good Excellent healing, a little adhesion to the wound at the end of healing Example PVP / PEO / CH ^d 9-10 days Good Excellent Healing Power Comparative example PVP ^e 10-12 days usually PVP conjugation to wound Comparative example Vaseline gauze More than 14 days Bad Vaseline residue in the wound a: hydrogel of Example 1 b: hydrogel of Example 2 c: 20 wt% PVP aqueous solution: 1 wt% CH (chitosan) acetic acid solution = 2: 1, gamma irradiation dose 35 kGyd: hydrogel of Example 3 e: 20 wt% PVP (polyvinylpyrrolidone) aqueous solution, gamma radiation dose 25 kGy

As can be seen in Table 3, the wound was almost healed after about 14 days, but the healing rate of the hydrogel-attached wound appeared faster. Vaseline gauze dries relatively quickly and clings to the wound. Some hydrogels slightly adhered to the wound, but the overall healing effect was much better than gauze, and a slightly added hydrogel did not adhere to the wound at all. Also, over time, hydrogels containing polyethylene oxide contained more water than other gels.

On the other hand, chitosan-added hydrogel had the best therapeutic effect and blood coagulated quickly.

Experimental Example 7 Skin Toxicity Test of Hydrogel

The hydrogels prepared in Examples 1 to 3 were applied to the skin of 1.5 × 1.5 cm 2 inside the human arm (10 test personnel) to determine the toxicity and side effects on the skin.

15 days after the hydrogel was applied, the skin had no side effects such as blistering or itching, and thus the hydrogel dressing according to the present invention was confirmed to not cause toxicity and side effects on human skin.

As described above, the method according to the present invention can prepare a hydrogel dressing having the characteristics of absorbing body fluid, preventing infection from bacteria, easy attachment to a wound or skin, transparency, handling, storage and sterilization. . In particular, the hydrogel dressing according to the present invention has adhesiveness, gel strength and the like suitable for treating wounds such as burns, and the use of chitosan or sodium alginate improves the wound healing effect. In addition, since the method according to the present invention crosslinks and sterilizes the polymer material by irradiation without using a crosslinking agent, there is an advantage of not causing any problems such as toxicity due to residual initiator or crosslinking agent.

Claims (11)

1) preparing an aqueous solution by mixing a polyvinylpyrrolidone synthetic polymer with chitosan, chitosan and polyethylene oxide, or sodium alginate and polyethylene oxide (step 1); 2) molding the aqueous solution of step 1 into a sheet form (step 2); 3) packing the sheet of step 2 (step 3); And 4) A method for producing a hydrogel dressing comprising the step (step 4) of irradiating radiation on the packaged sheet of step 3. The method of claim 1, wherein the polyvinylpyrrolidone synthetic polymer has a molecular weight of 200,000 to 1,300,000. The method of claim 1, wherein the polyvinylpyrrolidone synthetic polymer in step 1 comprises 3 to 25% by weight in an aqueous solution. The method of claim 1, wherein the polyethylene oxide in step 1 is prepared from 0.2 to 5% by weight of the aqueous gel dressing. The method of claim 1, wherein the chitosan in step 1 is prepared from 0.1 to 10% by weight of the aqueous gel dressing. 2. The method of claim 1, wherein the sodium alginate in step 1 is contained in an aqueous solution of 0.2 to 5% by weight. The method of claim 1, wherein the chitosan in step 1 is dissolved in 0.1 to 3 M acetic acid aqueous solution prepared by mixing with a polyvinylpyrrolidone aqueous solution or a mixed aqueous solution of polyvinylpyrrolidone and polyethylene oxide Way. The method of claim 1, wherein the radiation of step 4 is gamma rays (γ-rays) or electron beams (β-rays). The method of claim 1, wherein the radiation dose of step 4 is 20 to 100 kGy. The method according to claim 1, wherein when the polyvinylpyrrolidone synthetic polymer is mixed with chitosan and polyethylene oxide, the sheet of step 2 is first irradiated with 10-20 kGy of radiation to gel, and the formed gel is 0.1-1 M. Into the aqueous solution of sodium hydroxide to induce the immobilization and neutralization of chitosan, washed with distilled water and packaged, the method of producing a hydrogel dressing, characterized in that the second irradiation of the step 4. Hydrogel dressing prepared by the method of claim 1.