KR20210120484A - Anti-adhesion membrane with improved usability and producing method thereof - Google Patents

Abstract

The present invention relates to an anti-adhesion membrane with improved usability and a method for manufacturing the same. The anti-adhesion membrane comprises: a hydrophilic nanofiber sheet obtained by electrospinning a hydrophilic mixed polymer solution containing at least one hydrophilic natural polymer selected from the group consisting of chitosan, pullulan, gelatin, γ-PGA and alginate, and polyvinylpyrrolidone (PVP); and a mixed solution coating layer obtained by applying a mixed solution for application containing a surfactant or a moisturizing agent and a solvent to the nanofiber sheet and drying the same. The anti-adhesion membrane of the present invention has excellent adhesion with an even surface of the nanofiber sheet by applying a surfactant or moisturizing agent layer on the nanofiber sheet layer. The membrane has a clean internal environment and has no change in the physical property, appearance and convenience of use by moisture or blood in a non-contamination area without any change by external factors, so as to reduce a treatment time and not affect an operation time, thereby reducing the fatigue of doctors and nurses from long surgery and achieving the effect of reducing the burden of medical expenses on patients with less troubles of additional use.

Description

Anti-adhesion membrane with improved usability and producing method thereof

The present invention relates to an anti-adhesion film capable of preventing the adhesion of abnormal tissues, and more specifically, an anti-adhesion film with improved usability by applying a surfactant or a moisturizing agent to a nanofiber sheet prepared using an electrospinning method, and a method for manufacturing the same is about

Tissue adhesion refers to the association of abnormal fibrous connective tissue with other tissues and wounds that may occur during the natural healing process of wounds formed in the abdominal cavity after surgical laparotomy. Tissue adhesion is one of the unsolved complications in modern medicine, where many surgeries are performed, and adhesions between tissues and organs in the abdominal cavity frequently occur after laparotomy. Some of the adhesions are decomposed spontaneously, but in most cases, adhesions remain even after wound healing, causing pain with various sequelae to the patient. The causes of intestinal adhesions that occur after surgery include foreign substances introduced into the abdominal cavity, inflammatory response according to infection, tissue ischemia, blood coagulation, excessive tissue traction, rupture of the serous membrane, and rough surgery. The perfect way to do this is still unknown. According to statistical data, adhesions occur in different degrees in more than 93% of patients after laparotomy, causing chronic pain in patients, female infertility due to uterine and pelvic adhesions, and organ or tissue dysfunction. Reoperation is necessary and sometimes life-threatening.

There are three main methods of preventing adhesions known so far. The first method is a micro-surgical technique that minimizes wounds during open surgery. The second method is a chemical method in which an anti-inflammatory agent, a fibrin formation inhibitor, an anticoagulant, a proteolytic agent (eg, t-PA), etc. are added. The chemical method has a disadvantage in that some of the drugs cause a side effect of delaying the healing rate of the wound compared to the anti-adhesion effect. The third method is to use a physical barrier to wrap or cover the wound site after surgery to isolate it from the surrounding tissue, and many results have been reported that this method is very effective.

Examples of the use of physical barriers include a study investigating the possibility of anti-adhesion using a temperature-responsive polymer (PNIPAM-grafted hyaluronan/gelatin), an in situ cross-linkable hyaluronic acid (HA) hydrogel, and self A study using an auto-crosslinked hyaluronan derivative gel, a study using a UV cross-linked gelatin film, a study with polygalacturonic acid (PGA) inserted, a collagen film/gel , Research using SH/CMC and fibrin glue, sodium alginate (Alg) SCMC, polyethylene glycol-polypropylene glycol (PEC-PPG, Polyxamer) as anti-adhesion materials Study, study using poly(L-lactic acid)-PEG diblock copolymer film, study using chitosan-poloxamer gel complex, hyaluronic acid-carboxymethylcellulose Many research results have been reported, such as comparative experiments using Seprafilm, Dextran 40, and fibrinogen (Beriplast TM), and studies using SCMC-heparin.

Among previous studies on the prevention of adhesions using physical barriers, there are many research results that materials containing SCMC (sodium carboxyl methyl cellulose) and hyaluronic acid as main components are effective in preventing adhesions, but the clear mechanism of adhesion prevention is still unknown.

Cellulose and dextran are natural polymers, but they are known to cause foreign body reactions in the body because they are not components of the living body. It is known to have to be disassembled.

On the other hand, hyaluronic acid (USP 4,141,973) has a fast decomposition rate in vivo, so the shape maintenance ability required as a physical barrier is not satisfactory. Some of these anti-adhesion agents have been commercialized and used to inhibit the formation of adhesions between organs and tissues after surgery, and are currently absorbable oxidized regenerated cellulose (Interceed TC-7; Johnson and Johmson Medical Inc.), non-absorbable polytet. Polytetrafluoroethylene (PTFE, Gore-Tex; WLGore Co.), sodium hyaluronate/carboxymethyl cellulose (Serafilm, Genzyme Co.), etc. are used, and several layers of polyester and Neuro-tex dura-mak (Neuro-tex MANC NT, Textile Hi-Tech Co.) composed of polyurethane is used as an anti-neural adhesion agent. However, products made of synthetic polymers such as PTFE, polyester, and polyurethane are not decomposed in the living body, so it is not good for the human body from a long-term point of view.

In the recent development of other physical barriers to adhesion agent using a spray gel ^{™ (SprayGel ™; Confluent Surgical Inc.} ) is a surgical site of polyethylene glycol (PEG) when the hydrogel was then coated with the treatment is complete, is slowly decomposed to be absorbed adhesion film It is noteworthy in its form. However, polyethylene glycol, a synthetic polymer, is absorbed and discharged out of the body through the metabolic pathway, but it is rapidly absorbed and it is difficult to control the duration as a barrier to prevent adhesions.

Conventionally, as a technique for manufacturing nanofibers, composite spinning, melt blow spinning, flash spinning, electrospinning, and the like are known. Electrospinning is recognized as the most anticipated microfiber manufacturing technology in consideration of the diversity of applied polymers, the simplicity of the manufacturing process, the commercialization potential, and the possibility of application to various technologies.

Recently, research on nano-technology (NT) has been conducted competitively around the world, mainly in the United States. In particular, the electrospinning method is a spinning method in which a polymer jet is ejected by applying a high voltage to a polymer solution, and fibers having a nanoscale diameter are obtained while the solvent is volatilized. It has high specific surface area, porosity, high aspect ratio and flexibility. , it is easy to control the fiber diameter by controlling the spinning conditions. Nanofibers manufactured by electrospinning can be applied to various fields such as reinforcing agents, membrane materials for high-efficiency filters, functional fibers, and military supplies using antifouling functions. Recently, it is also attracting attention as a processing method of medical materials having high added value such as a scaffold.

In general, the electrospinning system can be roughly divided into a solution supply part of a fiber material, a high voltage supply part, and a collector part where nanofibers are formed. In addition, the radiation environment (humidity, temperature) should be able to be maintained in an optimal and constant condition. The solution supply part consists of a syringe pump and a syringe (or nozzle) part that accurately discharges a solution at a constant speed, and the characteristics of the fiber can be controlled according to the design of the syringe needle shape, diameter, material, etc. The high voltage supply part controls the voltage and current with an insulated cable composed of a (+) pole that charges the polymer solution with a high dielectric constant and a (-) pole where the charged solution is collected in the form of a nanofiber filament. In the collector part where the nanofibers are collected, the arrangement of the nanofiber strands can be adjusted according to the design of the shape, movement, speed, etc., and various shapes of materials can be manufactured according to the purpose.

The type of material used for electrospinning is generally a well-dissolved solution, and the properties of the polymer used during electrospinning have a great influence on fiber formation. Such solution properties include the concentration, viscosity, surface tension, Conductivity, dielectric properties, volatility, etc. The concentration of the polymer solution is closely related to the viscosity, and since the viscosity is a measure of the degree of entanglement and fluidity of polymer chains, it is known as an important factor affecting the shape, diameter, and spraying speed of fibers produced during electrospinning. have. Although there are differences depending on the polymer properties, it has been reported that fiberization is possible when the viscosity is about 0.5-50 poise, and when the viscosity is too high or low, fiberization does not occur. Electrospinning is a technology for manufacturing fibers of several nm to several μm by applying an electrostatic force to a polymer solution or melt and spun by a large potential difference between a charged polymer and a grounded current collector. It is a spinning technology that can be spun with a fast spinning speed and a small amount, can obtain a nonwovens form at the same time as spinning, and is easy to add additives.

Techniques have been proposed to use nanofibers, particularly nanofibers obtained by electrospinning a polymer solution, as a physical barrier to prevent tissue adhesion.

Professor Benjamin Chu of the United States tried to use PLGA, which is commonly used as a material for tissue engineering, as a basic material to manufacture biodegradable nanofibers containing antibiotics and use them as an anti-adhesion film.

Patent Registration No. 10-0785378 discloses a multi-layer structure consisting of a nanofiber-structured base layer formed by electrospinning a hydrophobic biodegradable, biocompatible polymer and a polymer layer formed by coating a hydrophilic bio-derived polymer on the surface of the base layer. Describes anti-adhesion agents.

As described above, many studies have been made on the anti-adhesion film and new technologies have been proposed, but the proposed technologies have their own problems and limitations, and the anti-adhesion effect is still insignificant. In addition, the currently used anti-adhesion membranes are very expensive and are a factor in increasing medical expenses. In the case of Korea, research on anti-adhesion agents has not been carried out yet, and most of them depend on imports. Therefore, the development of high-performance anti-adhesion agents that can effectively prevent adhesions in abnormal tissues has high added value and is in great demand worldwide.

However, most of the prior patents describe only the manufacturing and physical properties of the product. Physical properties such as tensile and absorbency are important to use as an anti-adhesion film, but the priority is that it is convenient for use by doctors and nurses. In other words, there are ways to simplify packaging so that it can be used easily, but the most necessary is to be able to use it without problems such as tearing or sticking when the nanofiber sheet comes in contact with water or blood in a state of a lot of moisture or blood due to the nature of the operating room. do.

In Patent Publication No. 10-2017-0089427, a porous polymer is dissolved in a solvent to prepare a first spinning solution, the first spinning solution is subjected to primary electrospinning to form a first nanofiber layer, and alginate and spirulina are added to the solvent. A second spinning solution is prepared by dissolving, and a second nanofiber layer is formed by secondary electrospinning of the second spinning solution on the first nanofiber layer to prepare a nanofiber support having a multilayer structure. This technology manufactures a multi-layered nanofiber support by performing electrospinning twice, and when electrospinning is performed twice, it takes a long time to manufacture, although it depends on the thickness, and due to the characteristics of electrospinning, which is sensitive to temperature and humidity, There is a problem in that there is a high possibility that defects occur during the car radiation treatment.

Republic of Korea Patent No. 10-0785378 Republic of Korea Patent Publication No. 10-2015-0004750 Republic of Korea Patent Publication No. 10-2017-0135264 Republic of Korea Patent Registration No. 10-2017-0128385 Republic of Korea Patent Publication No. 10-2018-0115594 Republic of Korea Patent Publication No. 10-2018-0003139

In order to solve the problems of the conventional anti-adhesion film as described above, the present invention is a nanofiber sheet prepared by mixing a hydrophilic natural polymer and polyvinylpyrrolidone (PVP) by applying a surfactant or a mixed solution of a moisturizing agent and a solvent and drying it. An object of the present invention is to provide an anti-adhesion film that does not cause deformation or problems by moisture or blood while effectively preventing adhesion of abnormal tissues.

In order to achieve the above object, the present invention comprises the steps of dissolving at least one hydrophilic natural polymer selected from the group consisting of chitosan, fullulan, gelatin, γ-PGA and alginate in a solvent to prepare a hydrophilic natural polymer solution; preparing a hydrophilic mixed polymer solution by adding polyvinylpyrrolidone (PVP) to the hydrophilic natural polymer solution; obtaining a hydrophilic nanofiber sheet by electrospinning the hydrophilic mixed polymer solution; preparing a mixed solution for application by mixing a surfactant or a humectant with a solvent; applying the mixed solution for application to the hydrophilic nanofiber sheet at 15 to 35 g/m 2 ; and drying the hydrophilic nanofiber sheet coated with the mixed solution for application at 100 to 160° C. for 1 to 2 minutes.

In the manufacturing method, it is preferable to mix the solvent and the surfactant or moisturizing agent in a weight ratio of 1-3:3-1.

In the preparation method, the hydrophilic natural polymer is preferably chitosan.

In the manufacturing method, the chitosan has a viscosity of 5 to 2,000 cps, and it is preferable that the deacetylation degree is 80% or more.

In the manufacturing method, the nanofiber sheet preferably has a cross-sectional average diameter of 100 to 300㎛.

The preparation method may further include adding a drug to the hydrophilic mixed polymer solution.

In addition, the present invention electrospinning a hydrophilic mixed polymer solution containing at least one hydrophilic natural polymer selected from the group consisting of chitosan, fullulan, gelatin, γ-PGA and alginate, and polyvinylpyrrolidone (PVP). The obtained hydrophilic nanofiber sheet layer and; It provides an anti-adhesion film with improved usability, comprising a mixed solution application layer dried by applying a mixed solution for application containing a surfactant or a moisturizing agent and a solvent to the nanofiber sheet.

In the anti-adhesion film, the hydrophilic natural polymer is preferably chitosan.

In the anti-adhesion film, the chitosan preferably has a viscosity of 5 to 2,000 cps, and a degree of deacetylation of 80% or more.

In the anti-adhesion film, the nanofiber sheet layer preferably has a cross-sectional average diameter of 100 to 300 μm.

In the anti-adhesion film, the hydrophilic nanofiber sheet layer preferably further comprises a drug.

The anti-adhesion film of the present invention has a nanofiber structure and blocks cell penetration and movement, thereby increasing the anti-adhesion ability and promoting wound healing. Thus, by applying a surfactant or moisturizing agent on the nanofiber sheet layer, which is easy to apply to various surgical operations, the surface of the nanofiber sheet is even, and the adhesion is excellent.

In addition, the anti-adhesion film of the present invention has a clean internal environment and does not change physical properties, appearance, and convenience of use by moisture or blood in a non-contaminated area, and does not change due to external factors, so treatment time is reduced and operation time is reduced. Because it does not have an effect, it can reduce the fatigue of doctors and nurses from long surgery, and it has the effect of reducing the burden of medical expenses on patients by reducing the problem of additional use due to abnormalities during use.

1 is a schematic cross-sectional view of the anti-adhesion film of the present invention.
2 is a photograph showing the nanofiber sheet before and after applying the mixed solution.
3 is a photograph showing the development of the nanofiber sheet coated and dried with the mixed solution of the present invention and the non-coated nanofiber sheet after impregnation with distilled water.
Figure 4 shows a photograph after applying the mixed solution by concentration to the nanofiber sheet of the present invention and a photograph after drying it.
5 is a surface electron micrograph before and after applying the mixed solution to the nanofiber sheet prepared by electrospinning in the present invention.
6 is a graph confirming the cytotoxicity of the dried product after applying the mixed solution to the nanofiber sheet of the present invention.

The anti-adhesion film with improved usability of the present invention is a mixture of at least one hydrophilic natural polymer selected from the group consisting of chitosan, fullulan, gelatin, γ-PGA and alginate, and a hydrophilicity containing polyvinylpyrrolidone (PVP). A hydrophilic nanofiber sheet layer obtained by electrospinning a polymer solution; It includes a mixed solution coating layer dried by applying a mixed solution for application containing a surfactant or a moisturizing agent and a solvent to the nanofiber sheet.

The method for preparing an anti-adhesion film having improved usability of the present invention comprises dissolving at least one hydrophilic natural polymer selected from the group consisting of chitosan, fullulan, gelatin, γ-PGA and alginate in a solvent to prepare a hydrophilic natural polymer solution ; preparing a hydrophilic mixed polymer solution by adding polyvinylpyrrolidone (PVP) to the hydrophilic natural polymer solution; obtaining a hydrophilic nanofiber sheet by electrospinning the hydrophilic mixed polymer solution; preparing a mixed solution for application by mixing a surfactant or a humectant with a solvent; applying the mixed solution for application to the hydrophilic nanofiber sheet at 15 to 35 g/m 2 ; and drying the hydrophilic nanofiber sheet coated with the mixed solution for application at 100 to 160° C. for 1 to 2 minutes.

Hereinafter, the present invention will be described in detail.

1. Preparation of nanofiber sheet

A mixed polymer solution in which a hydrophilic natural polymer and polyvinyl pyrrolidone (PVP) are mixed is electrospun to prepare a nanofiber sheet, which is a hydrophilic base layer having a nanofiber structure.

The nanofiber sheet is in direct contact with the wound site and has the advantage of very good safety for the human body and good biodegradability.

The hydrophilic natural polymer is at least one selected from the group consisting of chitosan, pullulan, gelatin, γ-PGA [Poly(γ-glutamic acid)] and alginate, more preferably.

As chitosan, it is particularly preferable to use chitosan having a viscosity of 5 to 2,000 cps and a degree of deacetylation of 80% or more.

Chitosan is a copolymer composed of N-acetylglucosamine and β-(1,4) glycosidic bonds of glucosamine and can be obtained by deacetylation of chitin. While chitin has a very limited solvent and is chemically inert, chitosan has the advantage that it is relatively reactive and can be prepared into various derivatives. Chitosan is biodegradable, non-toxic, and can be made in various forms such as powder, gel, and film, and the release of these components can be controlled through the combination of growth factors and extracellular matrix (ECM), and adhesion and differentiation of seeded cells. And because it can improve the proliferation, its application range is very wide. However, chitosan suffers from commercialization difficulties because the radiation persistence is low in the electrospinning method and the radiation is not excellent due to the solidification phenomenon.

In the present invention, these disadvantages of chitosan are supplemented and improved by introducing polyvinylpyrrolidone (PVP), which mixes well with chitosan, has excellent radioactivity, and is easily decomposed and discharged into the body. Polyvinylpyrrolidone (PVP) is a biocompatible polymer approved by the US FDA, and when polyvinylpyrrolidone (PVP) is added to chitosan, it has the advantage of excellent biocompatibility while solving the radioactive problem of chitosan nanofibers.

For the hydrophilic natural polymer and polyvinyl pyrrolidone (PVP), it is preferable to use 10 to 30 parts by weight of polyvinyl pyrrolidone (PVP) with respect to 100 parts by weight of the hydrophilic natural polymer, and polyvinyl phyllrolidone (PVP) for 100 parts by weight of the hydrophilic natural polymer. It is more preferable to use 10 to 20 parts by weight of vinyl pyrrolidone (PVP). When polyvinyl pyrrolidone (PVP) is used in less than 10 parts by weight, there may be a problem that it takes 4 weeks or more for the decomposition of nanofibers, and when used in excess of 30 parts by weight, the biodegradation period is short and the anti-adhesion ability may be lowered. can In particular, when using chitosan and PVP, it is preferable to use 10 to 20 parts by weight of polyvinylpyrrolidone (PVP) with respect to 100 parts by weight of chitosan, and more preferably to use 15 parts by weight. When polyvinylpyrrolidone (PVP) is used in less than 10 parts by weight, there is a problem in that it is difficult to form fibers due to the solidification of chitosan, and when used in excess of 20 parts by weight, it may be difficult to control the biodegradation time.

As a solvent for preparing a mixed polymer solution in which a hydrophilic natural polymer and polyvinylpyrrolidone (PVP) are mixed, one selected from trifluoroacetic acid, acetic acid and formic acid It is preferable to use the above, and it is more preferable to use a cosolvent obtained by mixing distilled water with acetic acid having relatively little toxicity.

The nanofiber sheet of the present invention may further include drugs such as anti-inflammatory agents and antibiotics, if necessary.

Anti-inflammatory drugs include aspirin (acetylsalicylic acid), ibuprofen, naproxen, sulindac, diclofenac, piroxicam, ketofuropen, diflunisal, nabumetone, etodolac, oxalupozin, India One or more nonsteroidal anti-inflammatory agents composed of metacin, tolmethine, and plant-derived polyphenols having anti-inflammatory action may be selected and used, but the present invention is not limited thereto. The plant-derived polyphenols include components having an anti-inflammatory action, such as rutin, EGCG, and catechin.

Antibiotics include penicillin, streptomycin, tetracyclin, kanamycin, chloramphenicol, actinomycin, ampicillin, bacitracin, and gracitracin. By selecting one or more of gramicidin, nalidixic acid, neomycin, nonactin, norfloxacin, patulin and terramysin It can be used, but is not limited thereto.

A solution was prepared by dissolving a hydrophilic natural polymer in a solvent, polyvinyl phyllrolidone (PVP) was added to the prepared hydrophilic natural polymer solution to prepare a hydrophilic mixed polymer solution, and the prepared hydrophilic mixed polymer solution was electrospinning to make it hydrophilic. A nanofiber sheet is obtained. When adding a drug, it is preferable to add the necessary drug to the mixed polymer solution.

In general, nanofibers have different diameters and properties depending on the concentration of polymer solution, spinning voltage, spinning distance, and flow rate during electrospinning.

In the present invention, electrospinning is performed by a conventional method, and it is preferable that the average cross-sectional diameter of the nanofiber sheet is 100 to 300 μm.

It may further include the step of drying in order to remove the residual solvent contained in the prepared nanofiber sheet. It is particularly preferable to sufficiently dry the drying in a vacuum oven at 25° C. for 24 hours.

2. Preparation of mixed solution for application

A mixed solution for application is prepared by mixing a surfactant or humectant with a solvent.

It is preferable to mix the solvent and the surfactant or humectant in a weight ratio of 1-3:3-1, and it is particularly preferable to mix the solvent and the surfactant or humectant in a weight ratio of 1:1.

As surfactants, BASF's ethylene oxide polymers (F-68, F-87, F-88, F-108, F-127, P-184), glycerin, diglycerin, polysorbate 20 (Poly sorbate 20), Tween 80, emulsifying wax, lanolin, cocamide MEA and CDE are selected and used. It is preferable to use an ethylene oxide polymer as a surfactant, and it is especially preferable to use P-184 among ethylene oxide polymers.

Moisturizers include propylene glycol alginate, methyl cellulose, sodium carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl starch, sodium alginate, ammonium alginate, potassium alginate, calcium alginate, sodium caseinate, guar gum, locust bean gum, xanthan gum, Cyclodextrin, gum arabic, gellan gum, carrageenan, karaya gum, casein, tara gum, tamarind gum, tragacanth gum, pectin, glucomannan, garty gum, arabinogalactan, purcelleran, pullulan, glucosamine, Carboxymethylcellulose, chitin, chitosan, sodium alginate, hyaluronic acid, amino acid, L-aspartic acid, L-sodium aspartate, DL-alanine, L-isoleucine, lysine hydrochloride, glycine, glycerin, L-glutamine, L-glutamic acid, L- One or more selected from sodium glutamate, pyrizic acid, L-threonine, sericin, serine, L-tyrosine, heparin, sodium chondroitin sulfate, sodium alginate and gelatin is used.

As the solvent, ethyl acetate, dimethylformamide, ethanol, distilled water, etc. may be used. Particular preference is given to using ethanol.

It is more preferable to use a surfactant among surfactants and moisturizers in the mixed solution.

3. Application of mixed solution for application

The prepared mixed solution for application is applied to the molded nanofiber sheet at 15 to 35 g/m 2 . It is more preferable to apply 20-25 g/m<2>.

As a method of treating the mixed solution, there are methods such as coating, spraying, immersion, etc., but it is preferable to apply. In the case of immersion, it is difficult to control the amount of treatment, and accordingly, a large amount of mixed solution is used, which increases the manufacturing cost of the product. For the application method, consider the surrounding environment in the range of 0.06~0.1T using an appropriate mesh roll considering the solid content of the mixed solution. Particularly preferably, using a 50-150 mesh roll, the coating speed is 10-20M/min.

4. Preparation of anti-adhesion film

An anti-adhesion film is obtained by drying the nanofiber sheet coated with the mixed solution for application at 100 to 160° C. for 1 to 2 minutes. It is more preferable to dry at 120-140 degreeC for 1-2 minutes.

A cross-sectional schematic diagram of the anti-adhesion film of the present invention is shown in FIG. 1 . In FIG. 1, reference numeral 10 denotes a mixed solution coating layer, and reference numeral 20 denotes a nanofiber sheet layer.

Hereinafter, the present invention will be described in more detail through specific examples. However, the following examples illustrate the present invention, and the scope of the present invention is not limited to the following examples.

<Production Example 1>

Preparation of chitosan/PVP nanofiber sheet

A solution was prepared by dissolving chitosan/PVP (9:1) in an aqueous acetic acid solution so as to be 10 wt/v%. As process factors, the voltage was fixed at 15~20kV, the spinning distance of 10cm, and the fluid velocity of 10ml/h, spun in a drum collector for 10 hours, and the humidity was maintained at 30% or less. In order to remove the residual solvent contained in the prepared nanofiber sheet, it was sufficiently dried in a vacuum oven at 25° C. for 24 hours.

<Example 1>

Ethanol was used as a solvent, and P-184 in ethylene oxide polymer was used as a surfactant. A mixed solution of a solvent and a surfactant in a weight ratio of 1:1 was added to the nanofiber sheet prepared in Preparation Example 1 at 20-25 g/m2 as An anti-adhesion film was obtained by coating.

<Example 2>

Ethanol was used as a solvent, and P-184 in ethylene oxide polymer was used as a surfactant. A mixed solution of a solvent and a surfactant in a weight ratio of 1:2 was added to the nanofiber sheet prepared in Preparation Example 1 at 20-25 g/m2 as An anti-adhesion film was obtained by coating.

<Example 3>

Ethanol was used as a solvent, and P-184 in ethylene oxide polymer was used as a surfactant. A mixed solution of a solvent and a surfactant in a weight ratio of 2:1 was added to the nanofiber sheet prepared in Preparation Example 1 at 20-25 g/m2 as An anti-adhesion film was obtained by coating.

<Comparative Example 1>

20-25 g/m 2 of ethanol as a solvent to the nanofiber sheet prepared in Preparation Example 1 An anti-adhesion film was obtained by coating.

<Comparative Example 2>

20~25g/m2 of P-184, a surfactant, on the nanofiber sheet An anti-adhesion film was obtained by coating.

<Comparative Example 3>

Ethanol was used as a solvent, and P-184 in ethylene oxide polymer was used as a surfactant. A mixed solution of a solvent and a surfactant in a weight ratio of 1:1 was added to the nanofiber sheet prepared in Preparation Example 1, 35-40 g/m2 An anti-adhesion film was obtained by coating.

<Experimental Example 1>

Comparison of nanofiber sheets before and after application of mixed solution

A photograph comparing the nanofiber sheet prepared in Preparation Example 1 and the nanofiber sheet (adhesion prevention film) coated with the mixed solution prepared in Example 1 is shown in FIG. 2 . The photo on the left of Figure 2 is a nanofiber sheet without applying the mixed solution, and the photo on the right is a nanofiber sheet coated with the mixed solution. When the mixed solution was applied, the nanofiber sheet did not show stickiness.

<Experimental Example 2>

Confirmation of deformation due to moisture

After impregnating the nanofiber sheet of Preparation Example 1 and the anti-adhesion film of Example 1 in a dish containing 20ml of distilled water for 30 seconds to submerge all sides, the change was confirmed. The results are shown in FIG. 3 .

As can be seen from the photo of FIG. 3 , the nanofiber sheet of Preparation Example 1 to which the mixed solution was not applied was severely deformed, whereas the anti-adhesion film of Example 1 to which the mixed solution was applied was hardly deformed.

<Experimental Example 3>

Nanofiber sheet drying time

The drying times of the anti-adhesion films of Preparation Example 1, Examples 1 to 3 and Comparative Examples 1 to 3 were checked, and the results are shown in Table 1 below.

room temperature 100℃ 140℃ Preparation Example 1 - - - Example 1 not dry 60-90 seconds 30-60 seconds Example 2 not dry 300 seconds 90 seconds Example 3 less than 60 seconds less than 40 seconds less than 30 seconds Comparative Example 1 less than 30 seconds less than 10 seconds less than 5 seconds Comparative Example 2 not dry not dry not dry Comparative Example 3 not dry 60-90 seconds 30-60 seconds

As shown in the results of Table 1, in the case of Example 3, the drying time was longer than the products of other Examples and Comparative Examples, and it took 4 to 5 minutes at 100°C. In Comparative Example 1, the drying time was too short, and in Comparative Example 2, drying was not performed. From these results, it was confirmed that the solvent and surfactant alone were not suitable for use.

<Experimental Example 4>

Change in appearance of anti-adhesion film

In the manufacturing process of the nanofiber sheet of Preparation Example 1, the anti-adhesion films of Examples 1 to 4 and Comparative Examples 1 to 3, after impregnating with the mixed solution and drying, the appearance change (shrinkage, hardening) was confirmed, and the result is shown in Table 2 and Figure 4 below.

Solvent: Surfactant Shrink rigidity Preparation Example 1 - ○ - Example 1 1:1 - - Example 2 1:2 - - Example 3 2:1 - - Comparative Example 1 - ○ - Comparative Example 2 - - - Comparative Example 3 1:1 - -

As shown in the results of Table 2, the anti-adhesion film of Comparative Example 1, in which only the nanofiber sheet of Preparation Example 1 and the solvent was applied, showed a phenomenon of product shrinkage after drying.

<Experimental Example 5>

Measurement of mechanical properties (tensile strength, elongation)

For the samples of Preparation Example 1, Examples 1 to 3 and Comparative Example 3, a load cell 50N using a universal test machine (Instron), the width of the specimen was 12 mm, and the length of the specimen (Gauge Length) ) was 100 mm, and the cross head speed was 100 mm/min, and the mechanical properties of each sample were measured. The results are shown in Table 3 below. In the case of the nanofiber sheet coated with the mixed solution, the tensile strength was similar to that of the fiber sheet without the mixed solution, and the elongation was higher. In the case of Example 2, the tensile strength and elongation were higher, but the drying process took more time.

Tensile strength (kgf/m㎡) Elongation (%) Preparation Example 1 0.43 9 Example 1 0.43 17 Example 2 0.46 27 Example 3 0.38 15 Comparative Example 3 0.40 19

< Experimental example 6>

Surface change of anti-adhesion film

The surface state of the samples of Preparation Example 1 and Examples 1 to 3 was measured using a scanning electron microscope (SEM). Confirmed. The results are shown in FIG. 5 .

In the photo of FIG. 5 , it can be seen that the surface of the anti-adhesion film of Examples 1 to 3 coated with the mixed solution was even compared to the nanofiber sheet of Preparation Example 1 to which the mixed solution was not applied.

<Experimental Example 7>

Cytotoxicity test

Preparation Example 1 (control), Example 1 (1:1), Example 2 (1:2), Example 3 (2:1), Comparative Example 1 (only solvent) and Comparative Example 2 (only surfactant) A cell culture test was performed to confirm the cell reactivity with respect to the sample.

For the experimental method, the method presented in the literature (ISO 10993 Biological evaluation of medical devices - Part 5: Test for in vitro cytotoxicity, Test on extracts) was used. As a cell line, rat fibroblasts (L-929, Korea Cell Line Bank) were used.

The results are shown in FIG. 6 . From the results of Figure 6, it can be seen that the samples of Examples 1 to 3 have almost no cytotoxicity with a cell viability of 95.1 to 96.2%.

<Experimental Example 8>

Check for change in stickiness

The degree of stickiness was checked for the samples of Preparation Example 1, Examples 1 to 3, and Comparative Example 3, and the results are shown in Table 4 below.

stickiness Preparation Example 1 Example 1 Example 2 Example 3 Comparative Example 3 One ○ × × △ × 2 ○ × × △ × 3 ○ × × △ × 4 ○ × × × × 5 ○ × × △ × ○: Sticky △: Slightly sticky ×: Not sticky

As shown in the results of Table 4, it was confirmed that stickiness appeared in the sample of Preparation Example 1 to which the mixed solution was not applied.

10: mixed solution coating layer
20: nano fiber sheet layer

Claims (11)

Dissolving at least one hydrophilic natural polymer selected from the group consisting of chitosan, fullulan, gelatin, γ-PGA and alginate in a solvent to prepare a hydrophilic natural polymer solution;
preparing a hydrophilic mixed polymer solution by adding polyvinylpyrrolidone (PVP) to the hydrophilic natural polymer solution;
obtaining a hydrophilic nanofiber sheet by electrospinning the hydrophilic mixed polymer solution;
preparing a mixed solution for application by mixing a surfactant or a humectant with a solvent;
applying the mixed solution for application to the hydrophilic nanofiber sheet at 15 to 35 g/m 2 ; and
A method of manufacturing an anti-adhesion film with improved usability, comprising drying the hydrophilic nanofiber sheet coated with the mixed solution for application at 100 to 160° C. for 1 to 2 minutes. According to claim 1,
The solvent and the surfactant or humectant is a manufacturing method, characterized in that mixed in a weight ratio of 1-3:3-1. According to claim 1,
The hydrophilic natural polymer is a manufacturing method, characterized in that chitosan. 4. The method of claim 3,
The chitosan has a viscosity of 5 to 2,000 cps, and the deacetylation degree is 80% or more. According to claim 1,
The nanofiber sheet is a manufacturing method, characterized in that the cross-sectional average diameter of 100 ~ 300㎛. According to claim 1,
The method, characterized in that it further comprises the step of adding a drug to the hydrophilic mixed polymer solution. Hydrophilic nanofiber sheet obtained by electrospinning a hydrophilic mixed polymer solution containing at least one hydrophilic natural polymer selected from the group consisting of chitosan, fullulan, gelatin, γ-PGA and alginate, and polyvinylpyrrolidone (PVP) layer;
An anti-adhesion film with improved usability, comprising a mixed solution application layer dried by applying a mixed solution for application containing a surfactant or a moisturizer and a solvent to the nanofiber sheet. 8. The method of claim 7,
The anti-adhesion film, characterized in that the hydrophilic natural polymer is chitosan. 9. The method of claim 8,
The chitosan has a viscosity of 5 to 2,000 cps, and an anti-adhesion film, characterized in that the degree of deacetylation is 80% or more. 8. The method of claim 7,
The nanofiber sheet layer is an anti-adhesion film, characterized in that the cross-sectional average diameter is 100 ~ 300㎛. 8. The method of claim 7,
The hydrophilic nanofiber sheet layer is an anti-adhesion film, characterized in that it further comprises a drug.

Images