KR101242574B1 - Hydrogels for wound dressing comprising nano-silver particle and preparation method thereof - Google Patents

Abstract

The present invention relates to a hydrogel with improved biocidal polymer and silver nanoparticles, the hydrogel of the present invention is a basic property for use in the treatment of wounds, such as burns, ie body fluid absorption, ease of attachment to the wound or skin, It has transparency, ease of handling and storage, and in particular, the effect of wound treatment is improved due to the toxin removal effect by silver (Ag) nanoparticles and the excellent disinfection effect against viruses and various bacteria, so that the wound treatment applied to skin regeneration treatment It can be usefully used as a dressing.

Description

Hydrogel for wound healing containing silver nanoparticles and method for preparing the same {Hydrogels for wound dressing comprising nano-silver particle and preparation method

The present invention relates to a hydrogel for wound treatment containing silver nanoparticles and a method for preparing the same.

In general, the wound healing process is divided into acute, restorative, and scar phases. Acute phase, also called exudation phase, is a stage in which a series of reactions are performed to remove them at damaged sites where tissues are destroyed or foreign substances are incorporated, and an inflammatory reaction and a blood coagulation reaction are involved. Restoration phase, also called proliferative phase, is the stage where new blood vessels are formed and damaged areas are increased to recover the damaged areas. In this period, active cell proliferation or active intercellular matter in collagen or proteoglycans in granulation tissue, which is a kind of connective tissue, is active. Synthesis takes place, epidermal cells acquire mobility, proliferate and regenerate epidermal tissue. The scarring step is a step in which active cell proliferation is slowed down, and collagen fibers are crosslinked to increase physical strength of the damaged area. Finally, the blood vessel system is also retracted and tissues different from the surrounding normal tissues are located at the damaged area. By repeating the above steps, the wound is healed.

As mentioned above, new granulation tissue must be created in all cases for the wound to heal. These granulation tissues are incompatible with necrotic tissue present on the wound and unable to absorb wound secretions. Therefore, removal of necrotic tissue should be preceded in the wound healing process. As a method of removing necrotic tissue, enzyme use and chemical treatment are known. However, these methods have a problem that affects normal cells as well as necrotic sites (enzyme use) and hassle in treating wound sites (chemical treatment). Therefore, research on methods and techniques for easily removing necrotic tissue from wounds without touching normal tissues at the stage for wound healing is required.

In general, it is well known that the treatment of wounds is much faster than the dry state when the wound is maintained in a water environment [Rake BA, Appl. Nurs. Res. 1998, 11, 174-182, efforts have been made to produce optimal hydrogels for wound healing.

Hydrogel is a material used for the purpose of burn treatment or skin regeneration that requires a constant wet state, and the hydrogel can usually be used for this purpose only when it contains 60% or more moisture. In the case of severe burn treatment, the result is transplantation of tissue transplanted with autograft or in vitro culture of the patient's fibroblasts, which requires considerable time until the procedure is performed. Blocking must be preceded. At this time, the hydrogel is compatible with blood, body fluids and biological tissues can be used as a wound dressing. In addition, hydrogels can also be used in contact lenses and cartilage.

In order to produce a hydrogel that can be used for this purpose, the selection of a polymer capable of forming a hydrogel must be preceded. The polymer should have a three-dimensional network structure, including hydrophilic functional groups such as carboxyl group (COOH), amide group (CONH ₂ ), amido group (CONH), sulfo group (SO ₃ H), while absorbing water and It should not dissolve. More specifically, the polymer that can be used in the hydrogel has water due to capillary and osmotic phenomena due to the nature of the structure to contain water, and due to the covalent structure between the polymer chain as well as electrostatic and lipophilic interactions It should be characterized by its insoluble in water.

In general, the polymer used in the hydrogel is made of synthetic polymer, natural polymer or a mixture thereof, and the synthetic polymer is hydrophilic such as polyvinyl alcohol, polyethylene oxide, polyhydroxyethyl methacrylate, polyvinylpyrrolidone, etc. The synthetic polymer may be selected and used, and the natural polymer may be selected from sodium carboxymethyl cellulose, gelatin, agar (agar), alginate, collagen, chitosan, and the like.

Methods of preparing such hydrogels include chemical methods and methods using irradiation technology. Among them, radiation is irradiated rather than chemical method prepared by adding a chemical crosslinking agent or initiator, eliminating the need for removing the chemical crosslinking agent or initiator, solving the toxicity problem due to the remaining of these substances, and simultaneously crosslinking and sterilization The use of radiation technology is drawing attention. In addition, the method using the irradiation technique has the advantage that not only do not apply heat in the cross-linking process, but also can be cross-linked even in the cooling state, it is possible to freely adjust the physical properties only by adjusting the radiation dose without changing the composition.

US Patent No. 5,389,376 discloses a method for preparing a wound dressing using a radiation crosslinking method. Specifically, a crosslinked hydrogel is prepared by mixing radiation with agar and polyethylene oxide to polyvinylpyrrolidone. However, the present invention has the advantages of the crosslinking method of the radiation, that is, the crosslinking and sterilization can be simultaneously promoted, but the strength of the hydrogel when mixing polyvinylpyrrolidone and agar is low, the compatibility is not good, the strength is weak There is a problem of tearing.

US Patent No. 5,480,717 discloses a hydrogel comprising a polymer film with an adhesive. Specifically, a polyvinylpyrrolidone aqueous solution is cast on a polymer film with an adhesive and irradiated with radiation to prepare a hydrogel. However, the hydrogel has a weak strength, but the adhesiveness is so strong that the polyvinylpyrrolidone remains when separating the hydrogel from the wound.

Japanese Patent Laid-Open No. 9-267453 discloses a technique of improving physical properties by using polyvinyl alcohol as a base material and adding another laminating agent thereto. Specifically, the polyvinyl alcohol is irradiated with gel to radiation, and after the packaging is irradiated again to prepare a hydrogel. However, the method has a limitation in improving physical properties, so it cannot be put in the packaging without irradiation, and thus radiation has to be irradiated twice. There is a problem of using a disinfectant separately for long-term use in the affected area. have.

Korean Unexamined Patent Publication No. 2001-0086864 discloses a method for producing a hydrogel based on polyvinylpyrrolidone and chitosan. Specifically, to irradiate the aqueous solution made by mixing polyvinylpyrrolidone and chitosan radiation to prepare a hydrogel for wound treatment. However, the hydrogel can not be used in patients with an allergic reaction to chitosan, there is a problem that the available time is short.

As described above, in order to develop a hydrogel that satisfies wound healing purposes, it must be able to absorb body fluids, be easily detachable from wounds or skin, and in particular, has a bactericidal power to prevent infection from various viruses and bacteria. Must be excellent In addition to good transparency and oxygen permeability, drug control, ease of handling and storage should be provided.

Thus, the present inventors while studying to produce a hydrogel with excellent sterilization power, preparing a hydrogel containing silver (Ag) nanoparticles, the silver (Ag) nanoparticles of the hydrogel to remove toxins and various viruses and bacteria It was confirmed that it can be usefully used as a dressing for wound healing by inhibiting growth excellently, and completed the present invention.

It is an object of the present invention to provide a hydrogel with improved sterilizing power, including a biocompatible polymer and silver nanoparticles.

Another object of the present invention is to provide a method for preparing the hydrogel.

Still another object of the present invention is to provide a wound dressing comprising the hydrogel.

In order to achieve the above object, the present invention provides a hydrogel with improved sterilization power, including a biocompatible polymer and silver nanoparticles.

In addition, the present invention comprises the steps of preparing an aqueous solution by adding a biocompatible polymer to purified water (step 1);

Pouring the aqueous solution prepared in step 1 into a tray to form a hydrogel in a sheet form (step 2);

Irradiating and crosslinking the hydrogel treated in step 2 with radiation (step 3);

Immersing the hydrogel treated in step 3 in an aqueous solution of silver nitrate and then irradiating with radiation to form silver nanoparticles in the hydrogel (step 4); And

It provides a method for producing a hydrogel with improved sterilization power comprising the step (step 5) of packaging the hydrogel treated in step 4.

Furthermore, the present invention provides a dressing for wound treatment comprising the hydrogel with improved sterilization power.

The hydrogel of the present invention has basic characteristics for use in treating wounds such as burns, that is, body fluid absorption, ease of attachment to wounds or skin, transparency, ease of handling, and storage properties, and in particular, removal of toxins by silver (Ag) nanoparticles. Due to the effect and excellent bactericidal effect against viruses and various bacteria, the effect of wound treatment is improved, so it can be usefully used as a dressing for wound treatment applied to skin regeneration treatment.

1 is a process chart showing a manufacturing process of a hydrogel according to an embodiment of the present invention.
Figure 2 is a graph measuring the degree of silver nanoparticles formed inside the hydrogel according to an embodiment of the present invention by UV-vis spectroscopy.
3 is a long-release scanning microscope photograph showing that silver nanoparticles are formed in the hydrogel according to an embodiment of the present invention.
Figure 4 is a graph measuring the bactericidal effect of the hydrogel in accordance with an embodiment of the present invention using a microbial growth measurement apparatus.

Hereinafter, the present invention will be described in detail.

The present invention provides a hydrogel with improved bactericidal power comprising a biocompatible polymer and silver (Ag) nanoparticles.

At this time, the content of the biocompatible polymer is 1 to 50% by weight, the content of the silver nanoparticles is preferably 0.001 to 5% by weight.

In the hydrogel according to the present invention, the biocompatible polymer should have a three-dimensional network structure, and by including a hydrophilic functional group, not only absorbs water but also does not dissolve in water. Therefore, the biocompatible polymer constituting the hydrogel may be a synthetic polymer such as polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, polyethylene oxide, or a natural polymer such as carrageenan, sodium carboxymethyl cellulose, gelatin, agar, alginate, chitosan, or the like. It can be used, it is preferable to use sodium carboxymethyl cellulose (CMC).

At this time, the content of the biocompatible polymer is preferably 1 to 50% by weight, more preferably 15 to 25% by weight, when less than 1% by weight is difficult to form a gel, more than 50% by weight If you do, there is a problem that the viscosity is too large to produce.

In the hydrogel according to the present invention, the silver nanoparticles have a bactericidal power to destroy and destroy the mucous membrane of bacteria when contacted with the bacteria in a non-irritant to the human body is used in various daily necessities that require a sanitary environment. The silver nanoparticles contained in the hydrogel of the present invention may be formed by irradiating an aqueous solution of silver nitrate with radiation.

At this time, the content of the silver nanoparticles is preferably 0.001 to 5% by weight, if less than 0.001% by weight does not exhibit sufficient sterilizing power, when the content of more than 5% by weight of the increase of more silver nanoparticles There is a problem that the silver nanoparticles are wasted because the sterilization effect is not improved.

In addition, the present invention provides a method for producing a hydrogel with improved sterilization power.

Specifically, the method for producing a hydrogel according to the present invention comprises the steps of preparing an aqueous solution by adding a biocompatible polymer to purified water (step 1);

Pouring the aqueous solution prepared in step 1 into a tray to form a hydrogel in a sheet form (step 2);

Irradiating and crosslinking the hydrogel treated in step 2 with radiation (step 3);

Immersing the hydrogel treated in step 3 in an aqueous solution of silver nitrate and then irradiating with radiation to form silver nanoparticles in the hydrogel (step 4); And

Packing the hydrogel treated in step 4 (step 5).

Hereinafter, the present invention will be described in more detail step by step.

In the manufacturing method according to the present invention, step 1 is a step of preparing an aqueous solution by adding a biocompatible polymer to purified water. Specifically, the aqueous polymer solution may be prepared by adding the biocompatible polymer to purified water and stirring at room temperature.

At this time, the content of the biocompatible polymer is 1 to 50% by weight, and preferably 15 to 25% by weight based on the total aqueous solution.

Examples of the biocompatible polymer of step 1 include synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid and polyethylene oxide, and natural polymers such as carrageenan, sodium carboxymethyl cellulose, gelatin, agar, alginate and chitosan. It can be used, it is preferable to use sodium carboxymethyl cellulose (CMC).

In the manufacturing method according to the present invention, step 2 is a step of making a sheet of hydrogel by pouring the aqueous solution obtained in step 1 to a tray. Specifically, the aqueous solution obtained in step 1 is poured into a sheet-shaped tray and left at room temperature, and when the temperature of the aqueous solution is lowered to 40 ° C. or lower, physical gelation is performed by the characteristics of the biocompatible polymer to form a gel sheet in the tray. do. In the present invention, the tray may be manufactured in a general shape or various sizes, thicknesses and shapes according to the use.

In the manufacturing method according to the present invention, the step 3 is a step of irradiating the hydrogel obtained in the step 2. Specifically, crosslinking the polymer by irradiation with radiation can yield a hydrogel of desired properties. In this case, the radiation used may be gamma rays, ultraviolet rays, electron beams, and the like.

It is preferable that it is 2-200 kGy, and, as for the irradiation amount of the said radiation, it is more preferable that it is 60-80 kGy. If less than 2 kGy can not be expected to form an effective cross-linking between the biocompatible polymers by irradiation, if it exceeds 200 kGy gel strength is too high due to the increase in the amount of cross-linking to decrease the flexibility of the hydrogel, the radiation of the polymer Deterioration problem occurs.

In the production method according to the invention, the step 4 is a step of irradiating the radiation gel after the hydrogel obtained in the step 3 in an aqueous solution of silver nitrate. Specifically, the hydrogel is immersed in an aqueous solution of silver nitrate for 1 to 3 hours so that the aqueous solution of silver nitrate is absorbed into the hydrogel, and then irradiated with radiation to dissolve the silver nitrate solution in silver nanoparticles and sterilize. At this time, the radiation used may be gamma rays, ultraviolet rays, electron beams, etc., the content of the silver nanoparticles is preferably 0.001 ~ 5% by weight.

It is preferable that it is 1-100 kGy, and, as for the irradiation amount of the said radiation, it is more preferable that it is 5-15 kGy. If it is less than 1 kGy, the formation of silver nanoparticles cannot be expected by irradiation. If it is more than 100 kGy, the gel strength is too high due to the increase in the amount of crosslinking, thereby decreasing the flexibility of the hydrogel and deteriorating the radiation of the polymer. A problem arises.

In the manufacturing method according to the present invention, step 5 is a step of packaging the hydrogel obtained in step 4. Conventional packaging materials may be used for the packaging, and for example, a polymer film such as polyethylene, polypropylene, polyvinyl chloride, nylon or polyester, aluminum foil, or a laminate of aluminum and a polymer film may be used.

Furthermore, the present invention provides a dressing for wound treatment applied to skin regeneration treatment using a hydrogel containing the silver nanoparticles.

The hydrogel of the present invention has basic characteristics for use in treating wounds such as burns, that is, body fluid absorption, ease of attachment to wounds or skin, transparency, ease of handling, and storage properties, and in particular, removal of toxins by silver (Ag) nanoparticles. Due to the effect and excellent bactericidal effect against viruses and various bacteria, the effect of wound treatment is improved, so it can be usefully used as a dressing for wound treatment applied to skin regeneration treatment.

Hereinafter, the present invention will be described in more detail with reference to examples. However, the following examples are merely to illustrate the present invention, but the content of the present invention is not limited thereto.

< Example  1> Contains silver nanoparticles Hydrated  Manufacturing 1

As a biocompatible polymer, sodium carboxymethyl cellulose (CMC, substitution rate of 1.2%) was purchased from Sigma Aldrich, and a silver nanoparticle-containing hydrogel was prepared by the same process as in FIG. 1.

20 wt% of sodium carboxyl methyl cellulose was added to 80 wt% of purified water and stirred until it was sufficiently dissolved to prepare a polymer aqueous solution. The aqueous solution was poured into a tray and left at room temperature to form a sheet-type hydrogel. The molded hydrogel was crosslinked by irradiating gamma rays with an intensity of 75 kGy per hour to make the gel strength suitable for the purpose of wound treatment. The crosslinked hydrogel was immersed in 100 ml of an aqueous solution of 0.01 M silver nitrate for about 1 hour, and once again irradiated with gamma rays at an intensity of 10 kGy per hour to form silver nanoparticles in the hydrogel. The hydrogel treated above was packaged with a laminate to prepare a silver nanoparticle-containing hydrogel.

< Example  2> containing silver nanoparticles Hydrated  Manufacture 2

The silver nanoparticle-containing hydrogel was prepared in the same manner as in Example 1 except that the hydrogel was irradiated with an aqueous solution of silver nitrate and irradiated with gamma rays at an intensity of 5 kGy per hour.

< Example  3> containing silver nanoparticles Hydrated  Manufacturing 3

The silver nanoparticle-containing hydrogel was prepared in the same manner as in Example 1 except that the hydrogel was immersed in an aqueous solution of silver nitrate and irradiated with gamma rays at an intensity of 3 kGy per hour.

< Example  4> Contains silver nanoparticles Hydrated  Manufacturing 4

The silver nanoparticle-containing hydrogel was prepared in the same manner as in Example 1 except that the hydrogel was immersed in an aqueous solution of silver nitrate and irradiated with gamma rays at an intensity of 1 kGy per hour.

< Comparative example  1> radiation Non-irradiation  Contains silver nanoparticles Hydrated  Produce

The silver nanoparticle-containing hydrogel was prepared in the same manner as in Example 1, except that the hydrogel was supported in an aqueous solution of silver nitrate and not irradiated with gamma rays.

< Experimental Example  1> Evaluation of Silver Nanoparticle Formation by Irradiation

UV-vis spectroscopy (PowerWave XS, PowerWave XS, In order to determine the degree of silver nanoparticle formation according to the intensity of irradiation and whether or not performed in the manufacturing step of the silver nanoparticle-containing hydrogel according to Examples 1 to 4 and Comparative Example 1 Bio-Tek) results are shown in FIG. 2, and images of silver nanoparticles formed inside the hydrogel using a long-emission scanning microscope (Sirion, FEI) are shown in FIG. 3.

As shown in FIG. 2 and FIG. 3, as the intensity of the radiation dose increased, the production amount of silver nanoparticles increased and was evenly dispersed.

< Experimental Example  2> Evaluation of bactericidal effect

In order to investigate the bactericidal effect according to the intensity and irradiation intensity of the irradiation in the preparation step of the silver nanoparticle-containing hydrogel according to the present invention was carried out as follows.

First, 9 ml of the culture solution was added to a test tube, and 1 ml of E. Coli bacterial solution was mixed, and then cultured for 24 hours while shaking at a speed of 150 ° C. at 37 ° C., and prepared in Examples 1 to 4 and Comparative Example 1. 1 g of hydrogel was added to each of the cells, and the results of measuring the extent of E. Coli bacterial growth by absorbance measurement (600 nm) using microbial growth measuring apparatus (S-3100, SCINCO) every 3 hours are shown in Tables 1 and 4 below. Shown in

Absorbance of E. Coli Bacteria (600 nm) sample 0 (h) 3 (h) 6 (h) 9 (h) 12 (h) 15 (h) Example 1 0 0.00706 0.0257 0.0301 0.0368 0.264 Example 2 0 0.00057 0.0312 0.0382 0.0337 0.0436 Example 3 0 0.005 0.0341 0.0336 0.0474 0.0522 Example 4 0 0.0156 0.0639 0.0939 0.1583 0.1908 Comparative Example 1 0 0.9683 1.4729 1.8434 1.972 2.0359

Figure 4 is a graph showing the results of measuring the bactericidal effect of the silver nanoparticle-containing hydrogel according to the present invention using a microbial growth measurement apparatus.

As shown in Table 1 and Figure 4, the hydrogels of Examples 1 to 4 containing silver nanoparticles produced by irradiation inside the hydrogel have a bactericidal effect as compared to the hydrogel of Comparative Example 1 not irradiated with radiation. Appeared to be excellent. This is considered to be an effect of increasing the surface area of bactericidal activity as silver (Ag) having bactericidal power due to irradiation is nanoparticles.

Therefore, the silver nanoparticle-containing hydrogel according to the present invention inhibits the growth of various viruses and bacteria as compared to the conventional hydrogel, and thus may be usefully used as a dressing for wound treatment.

Claims (16)

delete delete delete delete Preparing an aqueous solution by adding a biocompatible polymer to purified water (step 1);
Pouring the aqueous solution prepared in step 1 into a tray to form a hydrogel in a sheet form (step 2);
Irradiating and crosslinking the hydrogel treated in step 2 with radiation (step 3);
Immersing the hydrogel treated in step 3 in an aqueous solution of silver nitrate and then irradiating with radiation to form silver nanoparticles in the hydrogel (step 4); And
Method for producing a hydrogel containing silver nanoparticles comprising the step (step 5) of packaging the hydrogel treated in step 4.
The method of claim 5, wherein the content of the biocompatible polymer in the total amount of the aqueous solution of step 1 is 1 to 50% by weight.
The method of claim 5, wherein the biocompatible polymer is a synthetic polymer selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone polyacrylic acid and polyethylene oxide, and carrageenan, sodium carboxymethyl cellulose, gelatin, agar, alginate and chitosan. Method for producing a hydrogel, characterized in that one kind selected from the group consisting of natural polymers selected from the group consisting of.
8. The method of claim 7, wherein the biocompatible polymer is sodium carboxymethyl cellulose.
The method of claim 5, wherein the radiation is one selected from the group consisting of gamma rays, ultraviolet rays and electron beams.
The method of claim 5, wherein the radiation dose of step 3 is a method for producing a hydrogel, characterized in that 2 ~ 200 kGy.
The method of claim 10, wherein the radiation dose of step 3 is a method for producing a hydrogel, characterized in that 60 ~ 80 kGy.
The method of claim 5, wherein the time to support the aqueous solution of silver nitrate in step 4 is a method for producing a hydrogel, characterized in that 1 to 3 hours.
The method of claim 5, wherein the content of the silver nanoparticles in the total content of the hydrogel treated in step 4 is 0.001 to 5% by weight.
The method of claim 5, wherein the radiation dose of step 4 is a method of producing a hydrogel, characterized in that 1 ~ 100 kGy.
The method of claim 14, wherein the radiation dose of step 4 is 5 ~ 15 kGy.
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