WO2016122164A1 - Method for preparing wound covering material using biopolymer and wound covering material using biopolymer, prepared by same method - Google Patents

Abstract

Disclosed is a method for preparing a wound covering material using a biopolymer. The wound covering material prepared according to the present invention can have excellent effects of suppressing wound infection and preventing adhesion.

Description

Method for producing wound coating material using biopolymer and wound coating material using biopolymer manufactured using same

The present invention relates to a method for producing a wound coating material using a biopolymer and to a wound coating material using a biopolymer manufactured using the same. The wound coating material prepared according to the present invention may have excellent wound infection inhibitory effect and anti-adhesion effect.

Postoperative wound infections are a common hospital infection in surgical patients, accounting for 38% of all infected patients, and reported by the National Nosocomial Infection Surveillance (NNIS) system of the Center for Disease Control and Preservation (CDC) in the United States. Surgical Site Infection (SSI) is the third most common infection and accounts for 14-16% of all hospital infections in hospitalized patients. Other reports have reported that 27 million surgeries are performed annually in the United States, 675,000 of which are SSI, and 30 million surgeries are performed annually in Europe, of which about 900,000 are SSI. This is a negative factor in morbidity and recovery, which can cause serious problems for patients, practitioners and the overall healthcare industry, leading to longer hospital stays and increased health care costs. The development of surgical and sterile techniques over the past few years has significantly reduced the incidence of SSI in many countries, but this progress has led to other problems such as an increase in resistant strains and an increase in high-risk surgical patients. have. In particular, it has been shown to increase the risk of SSI in surgery of patients with diabetes or obesity, and the increase in morbidity in this area is of great concern to those involved. The World Health Organization predicts that the number of diabetics will increase from 171 million in 2010 to 366 million, so special care should be taken.

In addition to the strict sterile environment and the application of surgical techniques based on this, prophylactic antibiotic use may be considered in an effort to prevent SSI, but direct long-term administration of endovascular antibiotics may lead to antibiotic resistance and the risk of toxicity. Careful approach is required to apply because it can cause Thus, the emergence of topical use products (Gentacoll®, Collatemp G®), such as the absorbable gentamicin-collagen implants (GCI) described in US 1,321,818 and US 2014/0038915 A1, may help to address this situation. .

Topical use of Gentamicin may result in significantly higher concentrations in the wound than direct intravenous injection, while relatively low concentrations in the blood may reduce the risk of side effects or toxicity than the aforementioned intravenous infusions. In addition, this method avoids the resistance problems caused by long-term, low-dose administration of antibiotics and expects high concentrations of gentamicin to act as broad spectrum antibiotics. It has been confirmed to die and the use of these products for prophylactic or therapeutic purposes in several fields of surgical surgery (GI, cardiovascular and orthopeadic surgery) has been reported to reduce the risk of SSI.

In addition, postoperative adhesion refers to peripheral organs in which fibrous tissues are excessively formed in the healing process of wounds, such as inflammation, wounds, friction, and wounds, or blood is leaked and coagulated to separate them. Or the tissue sticking to each other, which can occur after all kinds of surgery. This phenomenon can cause severe clinical sequelae by attaching organs or tissues around the surgical site to each other in the postoperative recovery process.

In general, the incidence of postoperative long-term adhesions is reported to range from 55% to 93% (Ann. Royal Coll. Surg. Engl., 75, 147-153, 1993). After open surgery, adhesion occurs frequently, and some of them are spontaneously decomposed, but in most cases, adhesion remains after wound healing, causing various sequelae. There are many different types of sequelae. According to US statistics, the main symptoms of postoperative adhesion are small intestine occlusion 49% to 74%, infertility 15% to 20%, chronic pelvic disease 20% to 50%, It is known that up to 19% of intestinal perforations occur in subsequent surgeries (Eur. J. Surg., Suppl 577, 32-39, 1997).

The mechanism of intraperitoneal adhesions is described in detail in a paper by Granger (Infert.Reprod.Med.Clin.North Am., 5: 3, 391-404, 1994). It is triggered by fibrin, which occurs during the clotting process of blood. Inflammatory exudate is rich in fiber and forms blood clots on the wound surface. As the fibrous is broken down and the medium regenerates, the wound heals normally. Fibrin breakdown relies on the conversion of plasminogen to plasmin, a fibrinolytic enzyme, which is a tissue plasminogen activator (tPA) coexisting in the mesothelial and underlying substrate. If the fibrin is not degraded, inflammatory cells and fibroblasts penetrate into the fibroblasts, and the adhesions are organized. As such, coalescence occurs by a series of fibrin formation mechanisms and fibrin degradation mechanisms. The relationship between them is not simple, but is closely related to the healing process of the wound.

One of the methods to prevent adhesion is the study of anti-adhesion agents that use barriers to prevent the formation of adhesions between adjacent tissues by forming a physical barrier similar to surfactants during the healing of tissue wounds. Is actively underway. The anti-adhesion agents used for these barriers can be classified into two types. First, a membrane barrier including a film, a nonwoven fabric, and a sponge is a solution barrier.

Examples of the anti-adhesion material in the form of a film include oxidized-regenerated cellulose, expanded PTFE (expanded polyterafluoroethylene, ePTFE), modified hyaluronic acid and carboxymethylcellulose sodium, and chemical crosslinking agents. Solution type anti-adhesion materials include lactateringer solution, dextran-70 solution, heparin solution, carboxymethyl cellulose solution, hyaluronic acid solution, chondroitin sulfate solution, polyethylene glycol glycol solutions, poloxamer solutions, and the like. Among these solution-type anti-adhesion materials, lactateringer solution, dextran-70 solution, heparin solution, and the like, the main mechanism is to float the fibrous-covered surfaces so that they float together during healing of the peritoneum. These agents were used for the purpose of suppression, but they absorbed rapidly in the abdominal cavity and thus failed to obtain the effect of preventing adhesion (Am. Surg., 63, 775-777, 1983), and polyethylene glycol was not decomposed in vivo. Therefore, only materials with a low molecular weight that can be discharged through the absorption water metabolic pathway can be used, but absorption occurs excessively fast, so that the barrier role for preventing adhesion cannot be sustained long enough.

On the other hand, hyaluronic acid mentioned in U.S. Patent No. 4,141,973 is a linear polymer polysaccharide in which β-DN-acetylglucosamine and β-D-glucuronic acid are alternately bound, and shows excellent biocompatibility even when implanted or injected into a living body. It is known, but also has a limitation in performance as an anti-adhesion agent because it is decomposed and absorbed in a relatively fast time in vivo. In order to improve this, US Pat. No. 6,387,413 B1 prepared a hyaluronic acid gel composition by adding a polymer compound such as carboxymethyl cellulose in order to supplement the properties of the hyaluronic acid gel itself. Although the materials developed to this day show the possibility of preventing adhesion, they have the inconvenience of complicated removal of crosslinking agents or additives using chemical crosslinking methods, complicated process problems, and toxicity and safety problems.

Collagen, on the other hand, is one of the most abundant proteins on earth and can be extracted from almost any living organism. Collagen, which is used mainly in tissue engineering, is derived from cow skin, muscle or pig skin. However, collagen itself is a protein involved in the immune response, and collagen, which minimizes the immune response by elimination of telopeptide, which exhibits the main immune function, is also reported to be in the form of helical structure or amino acid sequence on the surface of collagen. Moreover, there is insufficient scientific evidence that bovine-derived collagen is completely safe for Bovine spongeform encephalopathy (BSE) factor.

The present inventors have made efforts to develop a material that can replace the expensive collagen material that plays a role as a support in gentamicin-collagen implants, and to develop a multifunctional material electrode that achieves the purpose of preventing adhesion and wound recovery after surgery. It has been found that biopolymers based on hyaluronic acid can be used to produce wound coatings with a smooth texture and even surface that inhibit wound infection and prevent adhesion.

According to the first embodiment,

Preparing a solution using an antibiotic and hyaluronic acid or a salt thereof;

Freezing the prepared solution under rotation; And

Disclosed is a method for producing a wound coating comprising the step of drying the frozen solution.

According to the second embodiment,

i) preparing a solution using an antibiotic and hyaluronic acid or a salt thereof;

ii) freezing the prepared solution;

iii) thawing the frozen solution;

iv) refreezing the thawed solution; And

v) A method of producing a wound coating comprising the step of drying the re-frozen solution is disclosed. In this embodiment, steps ii) to iii) may be repeated 2 to 6 times.

According to the third embodiment,

i) preparing a solution using an antibiotic and hyaluronic acid or a salt thereof;

ii) leaving the prepared solution at low temperature for at least 8 hours;

iii) freezing the cold left solution; And

iv) A method for producing a wound coating comprising drying the frozen solution is disclosed. According to the embodiment, the low temperature may be 0 to 10 ° C.

The hyaluronic acid wound coating prepared by the method according to the invention has a soft texture and an even surface morphology and can therefore replace collagen. In addition, the hyaluronic acid wound coating material produced by the method according to the present invention has an excellent wound infection inhibiting effect and an anti-adhesion effect.

1 shows a photograph of a wound covering prepared according to Example 1. FIG.

2 shows a wound covering prepared according to Example 2. FIG.

3 shows a wound covering prepared according to Example 3. FIG.

4 shows a wound covering prepared according to Example 4. FIG.

5 shows a wound covering prepared according to Example 5. FIG.

6 and 7 show wound wounds prepared according to Comparative Example 1. FIG.

8 shows a wound coating prepared according to Comparative Example 2. FIG.

9 shows a photograph of adhesion of rats receiving the control group according to Experimental Example 1. FIG.

10 shows a coalescence photograph of a pad receiving Example 5 according to Experimental Example 1. FIG.

Figure 11 shows the infection inhibition test results in the intestinal infection model according to Experimental Example 2.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. In this application, the terms "comprise" or "having" are intended to indicate that there is a feature, number, step, action, component, part, or combination thereof that is practiced, and that one or more other features or numbers are present. It should be understood that it does not exclude in advance the possibility of the presence or addition of steps, actions, components, parts or combinations thereof.

Unless otherwise defined herein, all terms used, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art. Terms such as those defined in the commonly used dictionaries should be construed as having meanings consistent with the meanings of the context of the related art, and should not be construed as ideally or excessively formal meanings.

The present invention provides a method for producing a wound coating material using hyaluronic acid as a biopolymer and a wound coating material produced by the method.

As used herein, the term "hyaluronic acid" is a linear polymer found in the same structure in almost all living organisms with molecular weight of millions of N-acetyl glucosamin and glucuronic acid as a basic unit and is mainly a component of the Extracellular Matrix. It is known as a polymer that does not have an immune response regardless of the extraction source because it has the same structure regardless of species and has been used in many fields such as degenerative arthritis, cataracts, wrinkle improvement, drug delivery, scaffold in stem cell field, and moisturizing maintenance ingredient of cosmetics. It is a safe natural polysaccharide used.

Initially, hyaluronic acid was extracted from livestock such as cows and chickens, but is currently produced by microbial fermentation, which is safe from harmful factors such as mad cow disease and bird flu, and it is possible to replace relatively expensive collagen.

However, as hyaluronic acid, it is crumbly and brittle after freeze-drying process that is performed when manufacturing products of general pads, patches, sheets, and so on. There is a problem that it is impossible to manufacture the same texture.

According to one embodiment,

Preparing a solution using an antibiotic and hyaluronic acid or a salt thereof;

Freezing the prepared solution under rotation; And

There is provided a method of producing a wound coating comprising the step of drying the frozen solution.

In the above embodiment, the antibiotic may be selected from the group consisting of cephalosporin-based, beta-lactam-based, aminoglycoside-based, macrolide-based, quinolone-based and tetracycline-based, but is not limited thereto.

In the above embodiment, the hyaluronic acid salt may be selected from the group consisting of sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, cobalt hyaluronic acid and tetrabutylammonium hyaluronate, but is not limited thereto.

In this embodiment, the molecular weight of the hyaluronic acid may be 10,000 to 3,000,000 Daltons.

In the above embodiment, the concentration of hyaluronic acid may be 0.1% to 5% (w / v).

In the above embodiment, the concentration ratio of the antibiotic and hyaluronic acid may be 2: 1 to 1:10.

In this embodiment, the pH of the solution may be 4.0 to 8.0.

According to another embodiment,

i) preparing a solution using an antibiotic and hyaluronic acid or a salt thereof;

ii) freezing the prepared solution;

iii) thawing the frozen solution;

iv) refreezing the thawed solution; And

v) A method of producing a wound coating comprising the step of drying the re-frozen solution is disclosed. In this embodiment, steps ii) to iii) may be repeated 2 to 6 times.

In the above embodiment, the antibiotic may be selected from the group consisting of cephalosporin-based, beta-lactam-based, aminoglycoside-based, macrolide-based, quinolone-based and tetracycline-based, but is not limited thereto.

In the above embodiment, the hyaluronic acid salt may be selected from the group consisting of sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, cobalt hyaluronic acid and tetrabutylammonium hyaluronate, but is not limited thereto.

In this embodiment, the molecular weight of the hyaluronic acid may be 10,000 to 3,000,000 Daltons.

In the above embodiment, the concentration of hyaluronic acid may be 0.1% to 5% (w / v).

In the above embodiment, the concentration ratio of the antibiotic and hyaluronic acid may be 2: 1 to 1:10.

In this embodiment, the pH of the solution may be 4.0 to 8.0.

According to another embodiment,

i) preparing a solution using an antibiotic and hyaluronic acid or a salt thereof;

ii) leaving the prepared solution at low temperature for at least 8 hours;

iii) freezing the cold left solution; And

iv) A method for producing a wound coating comprising drying the frozen solution is provided. In this embodiment, the low temperature may be 0 to 10 ℃.

In the above embodiment, the antibiotic may be selected from the group consisting of cephalosporin-based, beta-lactam-based, aminoglycoside-based, macrolide-based, quinolone-based and tetracycline-based, but is not limited thereto.

In the above embodiment, the hyaluronic acid salt may be selected from the group consisting of sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, cobalt hyaluronic acid and tetrabutylammonium hyaluronate, but is not limited thereto.

In this embodiment, the molecular weight of the hyaluronic acid may be 10,000 to 3,000,000 Daltons.

In the above embodiment, the concentration of hyaluronic acid may be 0.1% to 5% (w / v).

In the above embodiment, the concentration ratio of the antibiotic and hyaluronic acid may be 2: 1 to 1:10.

In this embodiment, the pH of the solution may be 4.0 to 8.0.

The hyaluronic acid wound coating prepared by the method according to the invention is expected to be able to replace collagen because of its smooth texture and even surface morphology.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, it will be apparent to those skilled in the art that the scope of the present invention is not limited to these examples.

<Example>

Example 1: Preparation of gentamicin-containing hyaluronic acid wound coating material (rotary freezing)

0.6% Gentamicin and 0.9% NaCl were dissolved in 0.3% (w / v) sodium hyaluronate solution and adjusted to pH 6.5 with dilute NaOH solution. The solution was then placed in a cylindrical flask and immersed in a -20 ° C bath and frozen at 100 rpm. After freezing was completed 72 hours using a freeze dryer (Fig. 1). As a result, a wound coating material having a smooth and smooth surface was obtained as can be seen from FIG. 1.

Example 2: Preparation of gentamicin-containing hyaluronic acid wound coating material (rotary freezing)

A gentamicin-containing hyaluronic acid wound coating material was prepared in the same manner as in Example 1 except that sodium hyaluronate was added at a concentration of 0.5% (w / v) (FIG. 2). As a result, a wound coating material having a smooth and smooth surface was obtained as can be seen from FIG. 2.

Example 3: Preparation of gentamicin-containing hyaluronic acid wound coating material (rotary freezing)

A gentamicin-containing hyaluronic acid wound coating material was prepared in the same manner as in Example 1 except that sodium hyaluronate was added at a concentration of 0.8% (w / v). (FIG. 3). As a result, a wound coating material having a smooth and smooth surface was obtained as can be seen from FIG. 3.

Example 4: Preparation of gentamicin-containing hyaluronic acid wound coating material (frozen / thawed)

0.6% Gentamicin and 0.9% NaCl were dissolved in 0.8% (w / v) sodium hyaluronate solution and adjusted to pH 6.5 with dilute NaOH solution. Then, a 50 ml dose in a square Petri dish was first frozen for 5 hours at -20 ° C, and thawed by standing at room temperature. After the thawing was completed, the second freezing for 5 hours at the same temperature as the freezing and then dried for 72 hours in a freeze dryer (Fig. 4). As a result, a wound coating material having a smooth and smooth surface was obtained as can be seen from FIG. 4.

Example 5: Preparation of gentamicin-containing hyaluronic acid wound coating material (cold standing)

0.6% Gentamicin and 0.9% NaCl were dissolved in 1.0% (w / v) sodium hyaluronate solution and adjusted to pH 6.5. Then, the petri dish was placed in a 50ml dose and left for 8 hours at a place of image 10 degrees, frozen at -20 ° C, and then dried in a freeze dryer for 72 hours (FIG. 5). As a result, as can be seen from FIG. 5, a wound coating material having a smooth surface was obtained.

Comparative Example 1: Preparation of gentamicin-containing hyaluronic acid wound coating material (conventional method)

0.6% Gentamicin and 0.9% NaCl were dissolved in 0.8% (w / v) sodium hyaluronate solution and adjusted to pH 6.5 with dilute NaOH solution. 50 ml dose in square petri dish was frozen for 5 hours at -20 ° C (Figure 6), and then dried in a freeze dryer for 72 hours (Figure 7).

As can be seen from FIG. 6 and FIG. 7, it was confirmed that a frozen or uneven surface was formed in the frozen solution, which caused the dry matter to be easily crushed or difficult to apply to the wound site.

Comparative Example 2: Preparation of gentamicin-containing hyaluronic acid wound coating material II

Dissolve 0.6% Gentamicin and 0.9% NaCl in 0.8% (w / v) sodium hyaluronate, 50ml volume in square Petri dish without pH adjustment, primary freezing at -20 ℃ for 5 hours, and petri dish at room temperature It was left to thaw. Then, after the thawing was completed, the second freezing for 5 hours at the same temperature as the freezing and then dried for 72 hours in a freeze dryer (Fig. 8). As a result, as can be seen from FIG. 8, it was confirmed that the surface of the wound coating material was uneven and easily crumbled.

Experimental Example

Experimental Example 1.Adhesion prevention test in rat cecum / abdominal scratch model

Rat caecum / abdominal abrasion model was used to evaluate the anti-adhesion performance of the wound covering prepared in the above example. Experimental animals used male Sparague-Dawley rat (SLC, Japan) of 7 weeks old per group. To induce adhesion, the experimental animals were anesthetized by injecting Ketamin.KCL into the abdominal cavity (0.1ml / 100g), and the abdominal hair was cut and sterilized with 70% ethanol and then opened along the centerline at about 4-5 cm. The caecum was then taken out and damaged by the 1.2 cm X 1.2 cm sterile gauze to the extent of the bleeding to the extent of the bleeding, and to the opposite peritoneum to the same size using a reagent spoon to the damage. The formation of adhesions was facilitated by fixing two locations 1 cm away from the frictional damage site with 5-0 nylon sutures to abut the two damaged surfaces.

In the negative control group, saline, and in the experimental group, the coating material prepared in Examples 1 to 5 and Comparative Examples 1 and 2 was 1 cm. X Cut to 1cm, attached to the damaged area and suture the peritoneal membrane and skin. After the surgery, the animals were fed with sufficient water and food, sacrificed for 1 week, and sacrificed to obtain an average value using the adhesion evaluation system ( Am. J. Obstet. Gynecol ., 146, 88-92, 1983). The results are shown in Table 1 below.

Evaluation of the degree of adhesion was classified from 0 to 5 according to the criteria (0: no adhesion, 1: one thin film type adhesion, 2: two or more thin film type adhesions, 3: point thick concentrated adhesions) , 4: plated centralized adhesions, 5: very thick adhesions with blood vessels formed or one or more plate-like thick adhesions).

Evaluation of the strength of coalescence was classified from 1 to 4 according to the criteria (1: coalescence that is film-type and dropped with very weak force, 2: coalescing requiring moderate force, 3: which can be released under considerable pressure). Coalescing, 4: coalescing is very strong and difficult to peel off or requires very high pressure).

Degree of adhesion Strength of adhesion Adhesion Area (cm ² ) Cohesion Area Reduction (%) Control 3.73 ± 0.46 3.00 ± 0.00 0.80 ± 0.16 0 Example 1 1.75 ± 1.07 ** 1.35 ± 0.84 ** 0.16 ± 0.08 ** 80.0 Example 2 1.65 ± 1.15 ** 1.30 ± 0.76 ** 0.12 ± 0.08 ** 85.0 Example 3 1.50 ± 1.08 ** 1.25 ± 0.84 ** 0.12 ± 0.12 ** 85.0 Example 4 1.40 ± 1.26 ** 1.20 ± 0.84 ** 0.07 ± 0.11 ** 91.1 Example 5 1.20 ± 1.30 ** 0.80 ± 0.84 ** 0.06 ± 0.10 ** 92.5 Comparative Example 1 1.75 ± 1.26 * 1.25 ± 0.96 ** 0.26 ± 0.09 ** 67.5 Comparative Example 2 2.25 ± 0.50 1.50 ± 1.00 * 0.27 ± 0.18 ** 62.5

Data were represented by mean ± S.D (n = 5).

*: p <0.05 versus None (negative control), **: p <0.05 versus None (negative control)

As shown in Table 1, in the group administered Examples 1 to 5 prepared by the manufacturing method according to the present invention, tissue adhesion was significantly reduced compared to the control group. This can also be confirmed through Figs. 9 and 10 showing the result of the adhesion according to the control and Example 5.

On the other hand, in the group administered Comparative Examples 1 and 2 prepared by the conventional manufacturing method showed a slight decrease in adhesion compared to the control group, the decrease in adhesion is reduced due to the non-uniform structure of the coating material It was confirmed that it was significantly lower than the group administered with Example 5.

Experimental Example 2 Infection Inhibition Test in Mouse Intestinal Infection Model

Intestinal infection model was used in Balb / C male mice to evaluate the inhibitory performance of the wound coating material prepared in Example 5. The infection control test group was divided into the control test group, the CLP test group, and the wound coating material administration group prepared in Example 5, and 10 male Balb / c mice (6 control test groups) were used for each group, and the wound coating material was 1 × 1. It was cut into a size of cm 2 and inserted. Specifically, the day before the test, the mouse abdomen was depilated, the next day the mouse was anesthetized for about 20 minutes by intraperitoneally administered Avertin at 300mg / kg. The anesthetized mouse abdomen was disinfected three times with alternating povidone and 70% ethanol. The abdomen was opened 2 ~ 3cm from the left side of the midline of the abdomen, and the cecum was removed. The CLP test group sutured the cecum back into the abdomen, and then sutured. The wound coating administration group prepared in Example 5 put the cecum into the abdomen and then sutured the prepared wound covering of ¹ × ¹ cm ² into the abdomen. The number of infected bacteria was collected from the mice 6 hours and 12 hours after surgery, and then cultured on LB plates. Colony counts were measured after 18 hours. The results are shown in FIG.

As shown in Figure 11, in the wound coating material administration group of Example 5 prepared by the manufacturing method according to the present invention, colonies were not produced when cultured ascites collected 6 hours after surgery, while CLP test group Was measured at 1.5 × 10 ³ cfu / ml. In the ascites 12 hours after the operation, 1.5x10 ³ cfu / ml and 1.5x10 ⁷ cfu / ml were measured in the Control test group and the CLP test group, respectively. It was confirmed that no colony was generated in the wound coating group.

Specific structural to functional descriptions are merely illustrated for the purpose of describing the embodiments of the present invention, and the embodiments of the present invention may be embodied in various forms and include all modifications and equivalents included in the spirit and scope of the present invention. It is to be understood to include to substitutes.

Claims (20)

Preparing a solution using an antibiotic and hyaluronic acid or a salt thereof; Freezing the prepared solution under rotation; And Method for producing a coating for inhibiting wound infection and adhesion prevention comprising the step of drying the frozen solution. The method of claim 1, PH of the solution is 4.0 to 8.0 method of producing a coating for inhibiting wound infection and preventing adhesion. The method of claim 1, The hyaluronic acid salt is sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, hyaluronic acid zinc, hyaluronic acid cobalt and hyaluronic acid tetrabutylammonium is a method for producing a wound infection inhibitory and anti-adhesion coating material. The method of claim 1, The molecular weight of the hyaluronic acid is 10,000 to 3,000,000 Daltons is a method for producing a wound infection suppression and adhesion prevention coating material. The method of claim 1, The concentration of the hyaluronic acid is 0.1% to 5% (w / v) method of producing a coating material for preventing wound infection and preventing adhesion. The method of claim 1, Said antibiotic is selected from the group consisting of cephalosporin-based, beta-lactam-based, aminoglycoside-based, macrolide-based, quinolone-based and tetracycline-based wound infection inhibition and anti-adhesion preventing coating material. i) preparing a solution using an antibiotic and hyaluronic acid or a salt thereof; ii) freezing the prepared solution; iii) thawing the frozen solution; iv) refreezing the thawed solution; And v) a method for producing a coating for inhibiting wound infection and preventing adhesion, comprising drying the re-frozen solution. The method of claim 7, wherein PH of the solution is 4.0 to 8.0 method of producing a coating for inhibiting wound infection and preventing adhesion. The method of claim 7, wherein The hyaluronic acid salt is sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, hyaluronic acid zinc, hyaluronic acid cobalt and hyaluronic acid tetrabutylammonium is a method for producing a wound infection inhibitory and anti-adhesion coating material. The method of claim 7, wherein The molecular weight of the hyaluronic acid is 10,000 to 3,000,000 Daltons is a method for producing a wound infection suppression and adhesion prevention coating material. The method of claim 7, wherein The concentration of the hyaluronic acid is 0.1% to 5% (w / v) method of producing a coating material for preventing wound infection and preventing adhesion. The method of claim 7, wherein Said antibiotic is selected from the group consisting of cephalosporin-based, beta-lactam-based, aminoglycoside-based, macrolide-based, quinolone-based and tetracycline-based wound infection inhibition and anti-adhesion preventing coating material. The method of claim 7, wherein The steps ii) to iii) is repeated 2 to 6 times the method for producing a wound infection suppression and adhesion prevention coating material. i) preparing a solution using an antibiotic and hyaluronic acid or a salt thereof; ii) leaving the prepared solution at low temperature for at least 8 hours; iii) freezing the cold left solution; And iv) A method of producing a coating for inhibiting wound infection and preventing adhesion, comprising drying the frozen solution. The method of claim 14, PH of the solution is 4.0 to 8.0 method of producing a coating for inhibiting wound infection and preventing adhesion. The method of claim 14, The hyaluronic acid salt is sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, hyaluronic acid zinc, hyaluronic acid cobalt and hyaluronic acid tetrabutylammonium is a method for producing a wound infection inhibitory and anti-adhesion coating material. The method of claim 14, The molecular weight of the hyaluronic acid is 10,000 to 3,000,000 Daltons is a method for producing a wound infection suppression and adhesion prevention coating material. The method of claim 14, The concentration of the hyaluronic acid is 0.1% to 5% (w / v) method of producing a coating material for preventing wound infection and preventing adhesion. The method of claim 14, Said antibiotic is selected from the group consisting of cephalosporin-based, beta-lactam-based, aminoglycoside-based, macrolide-based, quinolone-based and tetracycline-based wound infection inhibition and anti-adhesion preventing coating material. The method of claim 14, The low temperature is 0 to 10 ℃ the method for producing a wound infection suppression and adhesion prevention coating material.

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