KR20070118730A - Wound dressing materials with excellent ability to moisturized skin and method of manufacturing the same - Google Patents

Abstract

A wound dressing material with excellent ability to moisturize skin and a manufacturing method for the same are provided to prevent the loss of the chitosan due to moisture because the molecular weight of the chitosan is high. A wound dressing material with excellent ability to moisturize skin comprises chitosan nano fiber which contains chitosan as a principal ingredient and has a mean diameter of less than 1,000nm, and contains chitosan nano fiber web containing hyaluronic acid on which plural minute pores are formed. The hyaluronic acid is contained in the minute pores formed on chitosan nano fiber web. The molecular weight of the chitosan is 3,000 to 200,000. The degree of deacetylation is more than 70%. The chitosan nano fiber web is laminated on a synthetic fiber non-woven fiber having a mean diameter of more than 1,000nm.

Description

Wound dressing materials with excellent ability to moisturized skin and method of manufacturing the same

1 is a schematic diagram of an electrospinning apparatus for manufacturing a nanofiber web.

Figure 2 is an electron micrograph of the chitosan nanofiber web according to the present invention.

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a wound dressing having excellent moisturizing properties and a method for manufacturing the same, and more particularly, to a wound dressing having excellent biocompatibility, biodegradability, bacterial penetration resistance, breathability, and moisture retention properties, and a method for manufacturing the same.

Skin is an organ that protects the body from the outside, and if the skin is damaged, it is exposed to dangerous situations. When defects such as wounds and burns occur on the skin of the human body, they have the property of defending the defects and healing naturally.In this case, wound dressings are used as methods to effectively heal the defects and to speed up the healing. . These wound dressings should have excellent biocompatibility and should not have rejection of defects. They should be able to sufficiently absorb body fluids exuded from wounds. It should not have this toxicity. In addition, the wound surface and the cladding material should be properly contacted, the reactivity with other medicines used to prevent further infection of the defect area and to improve the wound healing ability and should be easy to mix.

Initially, non-degradable polymer materials such as polytetrafluoroethylene, cellulose acetate, silicone rubber, and polyurethane have been studied as materials for wound dressings. However, these non-degradable substances have a disadvantage in that some of the skin sinks during the healing process and remains in the skin permanently. In addition, the effective defense of the infection was difficult to cause unnecessary inflammation. In order to overcome this drawback, the development of wound coating materials using materials having excellent biocompatibility such as chitosan has recently been in progress.

Specifically, Korean Patent Laid-Open Publication No. 2002-0075539 proposes a wound dressing prepared by using a chitosan oligomer and an electrolyte composite. However, the wound dressing has a disadvantage in that physical defense against bacteria penetrating from the outside by using chitosan oligomer is difficult. In particular, the chitosan oligomer is water-soluble, and thus there is a disadvantage that the chitosan oligomer component may be dissolved in the exudates generated in the wound and removed by other gauze. In addition, if the voids are not physically provided separately, the air permeability to the affected part is lowered and the effect of wound healing is lowered.

On the other hand, Republic of Korea Patent Publication No. 10-2004-0052526 proposes a wound dressing made of a foam prepared using chitosan polymer. However, the wound dressing is not water-soluble and has excellent breathability, but it is difficult to physically defend against invasion of bacteria because the size of the pores of the foam is large and not uniform. In addition, due to the characteristics of the foam, the wound coating material itself may be damaged when bent or folded, and the wound portion has to be treated with a coating material having a considerable thickness. In addition, in the case of using the drug mixture in the wound dressing for the purpose of enhancing the wound healing effect, there is a disadvantage that the drug easily comes out by the pressure from the outside.

In order to overcome these shortcomings and provide better wound wound coating, Korean Patent Publication No. 10-2005-0032656, 10-2005-0048360, etc. propose a wound coating composed of chitosan nanofiber webs produced by electrospinning. . However, the above wound coating uses a solvent such as N-methyl morpholine oxide and hexafluoroisopropanol to dissolve chitosan, so the manufacturing cost is very expensive, and the wound is present in the state in which the solvent is mixed in the nanofibers during the electrospinning process. May cause rejection or inflammation at the site.

The purpose of the present invention is high molecular weight of chitosan, compared to the conventional chitosan wound material, there is no loss of chitosan due to moisture, and air is permeated easily through the fine pores on the wound coating, so that oxygen is supplied to the wound site smoothly. By using chitosan nanofibers, the surface area of chitosan is extremely wide, which greatly enhances the antimicrobial effects of chitosan, and prevents infection from external bacteria by preventing complex bacteria from complex pores of several nanometers to several micrometers. By adding hyaluronic acid to the three-dimensional pores of the nanofiber wound dressings, the amount of hyaluronic acid can be maximized and the slow release effect of hyaluronic acid by the micropores is excellent. To provide.

In addition, unlike the prior art, by using an acetic acid aqueous solution as a solvent in the electrospinning process is to provide a wound coating material having a low manufacturing cost.

The use of such chitosan nanofiber wound dressings containing hyaluronic acid is superior in biocompatibility compared to conventional polyurethane wound dressings, and is harmless to the human body even when the wound tissue is recessed into the skin tissue during the recovery of the wound site. Compared to wound dressings, the manufacturing process is simple and economical. Chitosan polymer is used to prevent the loss of chitosan due to moisture and the surface area of chitosan is extremely wide, so it is effective by chitosan and physically penetrates bacteria by complex micropores. The large amount of hyaluronic acid contained in the microvoids can be prevented, and the moisturizing effect of the wound is sustained, thereby increasing the recovery rate of the wound.

The wound coating material of the present invention for achieving the above object is composed of chitosan nanofibers whose main component is chitosan and an average diameter of 1,000 nm or less, and a plurality of micropores are formed and a chitosan nanofiber web containing hyaluronic acid is produced. It is characterized by including.

In addition, in the present invention, the wound coating is prepared by dissolving chitosan having a molecular weight of 3,000 to 200,000 and deacetylation degree of 70% or more in an acetic acid solution having a concentration of 1 to 30%, followed by electrospinning the polymer spinning liquid. To prepare a chitosan nanofiber web (Web), and then immersed in a hyaluronic acid solution, characterized in that for producing by squeezing.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

The present invention consists of chitosan nanofibers having a chitosan and an average diameter of 1,000 nm or less, and a plurality of micropores are formed and includes a chitosan nanofiber web containing hyaluronic acid.

More specifically, the present invention may be composed only of the chitosan nanofiber web (Web) containing hyaluronic acid, the structure of the chitosan nanofiber web (Web) containing the hyaluronic acid is laminated on a separate synthetic fiber nonwoven fabric It may be. The synthetic fiber nonwoven is made of synthetic fibers having an average diameter of more than 1,000 nm.

The average diameter of the chitosan nanofibers is more preferably 10 to 950 nm.

The molecular weight of chitosan constituting the chitosan nanofibers is preferably 3,000 to 20,000 and the degree of deacetylation is 70% or more.

If the molecular weight of chitosan is less than 3,000, the problem of chitosan dissolving and loss is caused by the exudates of the wound or other moisture. If the degree of deacetylation is less than 70%, the dilute acetic acid solution, which is a solvent, does not dissolve. The polymer spinning solution for this becomes difficult.

In general, chitosan is obtained by immersing shells of crustaceans, such as crabs and crayfish, in 5% aqueous solution of hydrogen chloride to remove calcium, and then putting it in 5-10% aqueous solution of caustic soda and heating to 100 ℃ to stir for 4-6 hours. After removing to obtain chitin, the chitin was added to 40 ~ 50% caustic soda solution and heated to 100 ° C. for 6 hours to deacetylate to prepare.

The hyaluronic acid has the following chemical structural formula.

Hyaluronic acid is a natural substance found in all living organisms, and it is contained in high concentrations in soft connective tissue, intraocular vitreous, cartilage, joint fluid, and skin tissue in the human body. have. As shown in Figure 5, hyaluronic acid is a high-viscosity substance between collagen, elastin, and fibrous tissue.

Hyaluronic acid is known to deliver essential nutrients from the bloodstream to skin cells, absorb moisture as much as possible to keep the skin moist, and act as a buffer and lubricant from physical and chemical damage.

The hyaluronic acid is contained in the micropores formed in the chitosan nanofiber web (Web). In addition, the present invention is the collagen, alginic acid, chondroitin sulfate, mephenamic acid, ibuprofen, flubiprofen, indobetacin, naproxen, together with hyaluronic acid in the micropores formed in the chitosan nanofiber web (Web) It may include a wound dressing containing one compound selected from the group consisting of metronidazole, tetracycline, minocycline, oxytetracycline, and mixtures thereof.

Next, look at the method for producing a wound dressing of the present invention.

First, a polymer spinning solution is prepared by dissolving chitosan having a molecular weight of 3,000 to 200,000 and deacetylation degree of 70% or more in an acetic acid aqueous solution having a concentration of 1 to 30%.

In preparing the polymer spinning solution, hyaluronic acid may be added to the aqueous acetic acid solution.

The concentration of the acetic acid aqueous solution is preferably 5 to 20% in consideration of electrospinning and the like.

In the present invention, a low-toxic and low-cost dilute acetic acid solution is used as a chitosan solvent instead of conventional solvents such as N-methylmorpholine oxide and hexafluoroisopropyl alcohol.

Next, the polymer spinning solution prepared as described above is electrospun using an electrospinning device as shown in FIG. 1 to prepare a chitosan nanofiber web.

Specifically, the polymer spinning liquid stored in the spinning liquid main tank 1 is supplied to the nozzle 3 under high voltage through the metering pump 2, and then the polymer spinning liquid is subjected to high voltage through the nozzle 3. Electrospinning toward the collector (4) to produce a chitosan nanofibers and chitosan nanofiber web consisting thereof.

At this time, each of the nozzle 3 and the collector 4 is loaded with a high voltage from the voltage generator 6 and the voltage transfer rod 5.

When a conventional synthetic fiber nonwoven fabric or the like is passed through the collector 4 at a constant speed during electrospinning, the electrospun nanofibers are laminated on the synthetic fiber nonwoven fabric in the form of a web.

The voltage applied to the nozzle 3 and the collector 4 during the electrospinning is appropriately adjusted according to the concentration of the polymer spinning solution, the thickness of the desired nanofibers, etc. within the range of several thousand to several hundred thousand volts.

The synthetic fiber nonwoven fabric is composed of synthetic fibers having an average diameter of more than 1,000 nm. In the case of not passing the synthetic fiber nonwoven fabric on the collector during the electrospinning chitosan nanofiber web (Web) itself is produced.

Next, the chitosan nanofiber web (Web) prepared as described above is immersed in a solution containing hyaluronic acid, and then squeezed to fix hyaluronic acid to the micropores of the web (Web) to produce a wound coating material of the present invention. Manufacture.

In the wound coating material of the present invention, chitosan nanofibers are prepared through electrospinning, but a dilute acetic acid aqueous solution is used as a solvent, and a conventional chitosan oligomer is used as a wound coating material prepared by containing hyaluronic acid in the prepared chitosan nanofiber web. There is no loss of chitosan oligomer generated from wound dressing manufactured by water, and it has excellent air permeability, and it is difficult to penetrate bacteria from the outside, and wound healing medicine is released through countless micropores. It is characterized by.

That is, the nanofiber web of the present invention is used as a wound coating material that promotes a healing effect on skin defects caused by wounds, burns and the like and effectively prevents bacterial infection from the outside.

The wound dressing of the present invention is made of chitosan, which is a natural material, and has excellent biocompatibility and antibacterial effect. In particular, the chitosan has a high surface area, which is a characteristic of nanofibers, and thus, the effect of chitosan is conventional. It is superior to the wound dressing by the treated nonwoven fabric and chitosan oligomer. In addition, the numerous pores of the chitosan nanofiber web has excellent air permeability, so that oxygen is smoothly supplied to the wound site, thereby facilitating cell proliferation and improving wound recovery rate. In addition, hyaluronic acid is added to the chitosan nanofiber web, but a large amount of hyaluronic acid can be added by the myriad three-dimensional micropores of the chitosan nanofiber web, and it has excellent sustained release effect to the skin, so that the hyaluronic acid is continuously wound for a long time. It is supplied to the site, so the skin's moisturizing effect is excellent, so that the recovery speed of the wound site can be faster. Hyaluronic acid is a skin component, and it is characterized by almost no side effects due to its excellent biocompatibility.

The wound dressing using the chitosan nanofiber web of the present invention is characterized in that it is produced by electrospinning. In the process of manufacturing by electrospinning, unlike the prior art, the manufacturing process is very economical and safe because only an aqueous acetic acid solution is used without using any toxic organic solvent. Acetic acid solution used as a solvent is effective in disinfection, sterilization and neutralization at the same time in the post-treatment process, and is effective and safer for human body. In addition, the wound coating material manufactured through the electrospinning and post-treatment process without the need to reattach the nanofiber web to a separate substrate by using the fabric or nonwoven fabric which is the basis of the wound coating material as the base material in the electrospinning process. The process is simple and convenient to use. In addition, the thickness of the nanofiber web that is volatilized and adhered to the substrate can be arbitrarily adjusted, and according to the extent of the wound, it is possible to manufacture a variety of products that can be suitably used according to the application.

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

However, the present invention is not limited by the following examples.

Example  One

Chitosan having a molecular weight of 30,000 and deacetylation degree of 95% was dissolved in an aqueous acetic acid solution of 5% concentration to prepare a spinning liquid having a chitosan concentration of 10%.

The spinning solution was electrospun onto the polyester nonwoven fabric passing through the collector 4 using the electrospinning apparatus of FIG. 1 to laminate the chitosan nanofiber web on the polyester nonwoven fabric.

At this time, the voltage during electrospinning was 30,000 V, and the moving speed of the polyester nonwoven fabric was 0.5 m / min.

Next, the laminate of the polyester nonwoven fabric and the chitosan nanofiber web was sterilized and sterilized by ammonia vapor, then immersed in a hyaluronic acid-potassium salt solution and squeezed at 30 PSi pressure with a mangled wound. The coating material was prepared.

The results of evaluating various physical properties of the prepared wound coating material are shown in Table 2.

Example  2- Example  5

The wound was the same as in Example 1 except that the molecular weight and deacetylation of chitosan, the concentration of acetic acid aqueous solution, the concentration of chitosan in the spinning solution, the voltage and substrate transfer rate during electrospinning, and the squeezing pressure were changed as shown in Table 1. The coating material was prepared.

The results of evaluating various physical properties of the prepared wound coating material are shown in Table 2.

Manufacture conditions division Chitosan Type Acetic acid solution concentration (%) Chitosan concentration in spinning solution (%) Voltage during electrospinning (V) Polyester nonwoven fabric moving speed (m / min) Squeezing Pressure (PSi) Molecular Weight Deacetylation Degree (%) Example 1 30,000 95 5 20 30,000 0.5 30 Example 2 5,000 80 5 20 20,000 0.3 25 Example 3 10,000 72 15 18 25,000 0.3 20 Example 4 55,000 85 20 15 30,000 0.3 20 Example 5 200,000 90 15 12 38,000 0.2 40

Comparative Example  One

A chitosan having a molecular weight of 30,000 and 95% deacetylation was dissolved in 8% hexafluoropropylene alcohol to prepare a spinning solution having a chitosan concentration of 10%.

The spinning solution was electrospun onto the polyester nonwoven fabric passing through the collector 4 using the electrospinning apparatus of FIG. 1 to laminate the chitosan nanofiber web on the polyester nonwoven fabric.

At this time, the voltage during electrospinning was 30,000 V, and the moving speed of the polyester nonwoven fabric was 0.5 m / min.

Next, the laminated body consisting of the polyester nonwoven fabric and the chitosan nanofiber web was sterilized and sterilized with ammonia vapor to prepare a wound coating material.

The results of evaluating various physical properties of the prepared wound coverings are shown in Table 2.

Properties of wound dressing division Weight change rate (%) Moisture permeability (g / ㎡ / day) Bacteriostatic rate (%) Skin moisture rate (%) Treatment effect Example 1 2 21,000 99.9 50 10 Example 2 6 18,000 99.8 40 9 Example 3 4 19,000 99.6 40 10 Example 4 One 20,000 99.7 45 10 Example 5 0.2 21,000 99.9 50 10 Comparative Example 1 One 21,000 99.7 30 5

Various physical properties of Table 2 were evaluated by the following method.

Chitosan's moisture resistance

The epithelial cladding was immersed in water at 40 ° C. and left to stand for 24 hours, followed by natural drying to evaluate the weight change of the wound cladding.

The weight change rate was calculated | required through the following formula.

W0: Weight of wound dressing before immersion in hot water at 40 ℃ (number of g)

W1: Weight of wound dressing after natural drying after soaking in 40 ℃ hot water for 24 hours (number of grams)

Breathability ( Breathable )

Moisture permeability was evaluated for wound dressings. Since the wound coating having excellent moisture permeability will also have excellent breathability, the evaluation of breathability can be evaluated as the moisture permeability. The method of evaluating moisture permeability is to evaluate the number of grams of moisture passed after 24 hours of application of moisture to a fabric under a certain pressure, according to Korean Industrial Standard KS K 0594.

Antibacterial Bacteriostatic rate )

Antimicrobial activity against bacteria is evaluated according to Korean Industrial Standard KS K 0693-2001. That is, the bacteriostatic reduction rate by culturing staphylococcus and pneumococci 2 and bacterial counts is evaluated for wound coatings of Examples and Comparative Examples.

· Skin moisture

The degree of drying or moisturizing the skin according to the use of wound dressings was evaluated using a skin moisture meter indicating the water content as a percentage. That is, after anesthesia for an experimental rat weighing 250g, a square wound having a length of 3cm and a thickness of 0.3cm on one side is cut in parallel with the spine and wound wound is attached to the incision. It was. After 5 days after closure, the skin moisture content of the wound was measured using a skin moisture meter. The measurement was performed four times for the same site and the average value was used.

Comprehensive Wound  Treatment effect

In order to evaluate the overall therapeutic effect of wound dressings, the recovery process of artificially wounded rats was visually evaluated as in the test of skin moisturizing effect evaluation. In the visual evaluation of the wound recovery after 7 days of wound dressing prescription, the evaluation of the incidence of inflammation and the reconstruction of skin tissue was comprehensively evaluated, and the grade was divided into 10 stages from low effect (1) to high effect (10). .

As shown in Table 2, in the case of using the wound coating by the chitosan nanofiber web containing the hyaluronic acid of Examples 1 to 5, the weight change rate was 10% or less and the loss of chitosan by moisture was low and the moisture permeability was 18,000. It is possible to pass a large amount of water or air, oxygen and the like more than g / ㎡ / day. In addition, the extremely large surface area of chitosan nanofibers maximize the antimicrobial effect, the bacteriostatic reduction rate exceeds 99.5%. In addition, it has excellent skin moisturizing effect by hyaluronic acid, absorbs the exudates from the wound and moisturizes the skin to maintain the moisture level of 40% or more, accelerating the growth rate of skin cells. Due to these effects, when evaluated 7 days after the treatment of wound dressings, the therapeutic effect was evaluated as having a very high therapeutic effect with more than 9 steps.

However, as shown in Comparative Example 1, when hexafluoropropyl alcohol was used as the solvent, there was little loss of chitosan, excellent breathability, and excellent antibacterial activity, but a small amount of hexafluoropropyl alcohol, a solvent, remained in the nanofibers. It stimulated the skin, lowered the moisture content of the skin, and the treatment effect remained at the fifth stage in the comprehensive evaluation.

If the chitosan nanofiber web containing hyaluronic acid of the present invention is used as a wound coating material, the chitosan nanofibers may be used during the healing process due to excellent biocompatibility compared to the wound coating material made of a non-degradable material such as polyurethane. There is almost no side effect due to non-degradability or toxic substances generated during decomposition even if it is depressed in the tissue, and exudates or other exudates generated from the wound site due to the use of high molecular weight chitosan compared to the conventional wound dressing using chitosan. There is almost no loss of chitosan due to moisture, and the extremely wide surface area by chitosan nanofiber web maximizes the wound healing effect by chitosan, and infiltrates external bacteria by innumerable micropores of the chitosan nanofiber web. Can be physically prevented and The property is extremely excellent in the smooth supply of oxygen to the top window is greater healing effect of the cell proliferation. In addition, by containing hyaluronic acid in the chitosan nanofiber web, the effect of supplying moisture to the wound site is extremely excellent, preventing the wound from drying out, and the early recovery effect of the wound site can be expected. In particular, by placing hyaluronic acid in a large amount of micropores of the chitosan nanofiber web, it can contain a large amount of hyaluronic acid and has a sustained release effect so that hyaluronic acid can be supplied to the wound site for a long time to maintain a moisturizing effect for a long time. To ensure that

By using the wound dressings to which the chitosan nanofiber web containing the hyaluronic acid is applied, the early recovery of the wound site can be expected and the secondary disease caused by bacterial infection can be prevented.

Claims (11)

It is composed of chitosan nanofibers whose main component is chitosan and its average diameter is 1,000 nm or less, and a plurality of micropores are formed, and it has excellent moisture retention wound coating, which comprises a chitosan nanofiber web containing hyaluronic acid. . The wound coating material of claim 1, wherein the hyaluronic acid is contained in the micropores formed in the chitosan nanofiber web. The wound coating material having excellent moisturizing properties according to claim 1, wherein the chitosan has a molecular weight of 3,000 to 200,000. The wound dressing having excellent moisturizing properties according to claim 1, wherein the deacetylation degree of chitosan is 70% or more. The method according to claim 1, wherein the collagen, alginic acid, chondroitin sulfate, mefenamic acid, iburofen, flubiprofen, indobetacin, naproxen, metronidazole, tetracycline, together with hyaluronic acid in the chitosan nanofiber web A wound dressing having excellent moisture retention, characterized by containing at least one selected from minocycline, oxytetracycline, and mixtures thereof. The wound coating material according to claim 1, wherein the chitosan nanofiber web containing hyaluronic acid is laminated on a synthetic fiber nonwoven fabric having an average diameter of more than 1,000 nm. The wound dressing according to claim 1, wherein the wound dressing consists only of a chitosan nanofiber web containing hyaluronic acid. Chitosan having a molecular weight of 3,000 to 200,000 and deacetylation degree of 70% or more was dissolved in an acetic acid aqueous solution of 1 to 30% concentration to prepare a spinning solution, followed by electrospinning the polymer spinning solution to prepare a chitosan nanofiber web. Then, the method of producing a superior moisturizing wound coating, characterized in that the squeezed after immersing it in a hyaluronic acid solution. The method for producing a wound dressing according to claim 8, wherein hyaluronic acid is added to the polymer spinning solution. 10. The method of claim 8, wherein the polymer spinning solution is electrospun onto a synthetic fiber nonwoven fabric passing through the collector (4). The wound coating material of claim 10, wherein the synthetic fiber nonwoven fabric is composed of synthetic fibers having an average diameter of more than 1,000 nm.

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