KR100546793B1 - Foam dressing using chitosan and Method of preparing the same - Google Patents

Abstract

The present invention relates to a foam dressing material using chitosan, and more particularly, freeze-drying an acidic aqueous solution of chitosan containing glycerol, additionally PEG or DMSO, to obtain a chitosan structure on the foam dressing, neutralizing and washing to completely remove residual acid. It relates to a method for producing a foam dressing material using chitosan prepared by removing and freeze-dried again, and to a foam dressing material prepared by the method, which is manufactured using only chitosan and natural polymers with small pores of a predetermined size. In addition, its elongation and tensile strength are dramatically increased and its absorbency is excellent, which is useful for wound coating materials and other tissue engineering structures.

Chitosan, Foam Dressing Material, Glycerol, PEG, DMSO, Lyophilization

Description

Foam dressing using chitosan and method of preparing the same             

Figure 1 is a schematic cross-sectional view of the chitosan foam dressing material consisting of the outer, inner absorbent layer and the microporous wound surface contact layer according to the present invention.

Figure 2 is a scanning micrograph of both surfaces and cross-section of the chitosan foam dressing material according to the present invention.

(Explanation of symbols for the main parts of the drawing)

1 ... outside

2 ... the inner absorbent layer of foam dressing material

3 ... wound surface contact layer

4 ... outer surface

5 ... wound surface contact layer surface

6 ... cross section of inner absorbent layer

The present invention relates to a method for producing a foam dressing material using chitosan, and a foam dressing material prepared by the method, and more particularly, freeze-drying an acidic aqueous solution of chitosan containing glycerol, additionally PEG and / or DMSO, onto a foam dressing. The present invention relates to a foam dressing material using chitosan, which is prepared by obtaining, neutralizing and washing a chitosan structure to completely remove residual acid and freeze drying again.

Skin is the body that has the largest surface area in the body and functions as an immune function. It protects against various harmful environments such as microorganisms, ultraviolet rays, and chemicals, and prevents dehydration and regulates body temperature by inhibiting water evaporation. It must play a role, be strong in physical stimuli, be resilient, and fulfill its role while the human body is living.

However, skin damage caused by various causes such as severe burns, trauma, wounds, pressure sores and skin diseases is common.For example, wounds that cannot be primaryly sutured are inevitable for skin transplantation, leaving serious defects in performing such functions. do. Therefore, repair of damaged skin tissue is an important problem, and as a method for this, autograft transplanting the patient's own skin, homograph or allograph transplanting the skin of another person, animal skin There are three ways of transplanting xenografts. Among these methods, autograft is the most ideal, but if the burn area is extensive, there are limitations in securing the tissue, leaving new wounds at the collection site, and new trauma to the healthy area where the skin is removed. There is a problem that the pain increases and the time to cure is prolonged. Especially for severe burns, there are not enough healthy skin available for transplantation, so several transplants are needed. On the other hand, these allografts serve to help the movement and healing of cells around the wound rather than permanent engraftment. The skins obtained from the carcasses in the United States and China can be used as a temporary protective agent by cryopreserving the skin obtained from the carcasses in glycerol. It can also be used in the form of de-epidermized dermis, which completely removes cells that can cause an immune response.

In the case of xenotransplantation, the supply of human skin donors is insufficient and alternatively, freeze-dried pig skin is used. In this case, the supply of skin sources is stable, but there are disadvantages such as a hyperacute rejection reaction. Therefore, there is an urgent need for the development of artificial skin that has a function of protecting the human body by blocking the external environment such as bacteria and having a minimum of adequate moisture permeability.

Artificial skin is roughly divided into two types: temporary skin equivalent, so-called wound coating, and permanent skin equivalent for cultured skin or implantation. Wound coverings protect temporary lesions until the skin damaged by burns or trauma recovers, and prevents leakage of water from the body, absorption of exudates, and prevention of invasion of bacteria and infection from the outside. Dressing materials for wound dressings include film type, hydrocolloid type, hydrogel type, nonwoven fabric type and polyurethane foam type, and are made of porous membrane using collagen or natural polysaccharide, alginate, chitin, chitosan or lyophilized pig skin. Eggplant products are used clinically. On the other hand, cultured skin, also known as bioartificial skin, is applied to a wide range of burns of 3 degrees or more, or skin ulcers caused by diabetes, which have lost the ability to regenerate by surrounding magnetic cells. In a more advanced method, artificial skin obtained from a patient's own cells, that is, cells constituting each layer of the skin are collected and expanded in vitro, and then collagen solution extracted from bovine gel is mixed with the dermal layer cells to shrink. The skin obtained by layer differentiation of epidermal cells on the manufactured artificial dermis may be used. The artificial skin using the gel dermis is inoculated into a tissue engineering construct made mainly of suitable biodegradable synthetic polymer or natural polymer, and is prepared by using magnetic cells by inducing the formation of the tissue. There is no merit that can control the size of the skin. At this time, the natural or synthetic polymer material used as the structure for tissue engineering should provide a biomimetic environment capable of fully exhibiting the original functions while having the cell growth ability. Tissue engineering structure is made by using natural polymer directly or compounding with synthetic polymer.

As a wound coating material or tissue engineering structure material used for skin transplantation, US Patent No. 5143071 describes a method for preparing hydrogel by photocrosslinking an aqueous solution prepared by dissolving polyvinylpyrrolidone and polyethylene oxide using light. And several hydrogels are disclosed; U. S. Patent No. 4,773, 409 discloses a process for preparing a hydrophilic polyurethane foam dressing agent by mixing polyethylene glycol, isocyanate, catalyst, water, water soluble or water swellable polymers by one-shot process; U. S. Patent No. 4,375, 519 discloses a method of making a wound dressing prepared by adding hydrophilic absorbable particles to a polytetrafluoroethylene (PTFE) fibril matrix; And US Pat. No. 4,563,184 use poly (2-hydroxyethyl methacrylate) (PHEM) as a polymer, polyethylene glycol as an organic solvent and dimethyl sulfoxide as a hydrogen bond plasticizer. The present invention discloses a synthetic wound dressing and a wound dressing prepared using a synthetic polymer such as silicone gauze, crosslinked polyvinyl alcohol sponge, polyamide, polyester fiber, polypropylene fiber, and rayon fiber. Due to problems such as rejection, lack of mechanical properties and adhesion, it does not function as an artificial skin.

On the other hand, recently, artificial skin manufactured using collagen has been introduced in the United States, Europe, Japan and the like. For example, US Patent No. 4,294,214 discloses an artificial skin prepared from collagen or chemically modified collagen in the form of a gel or a sheet. Skin; U. S. Patent No. 4,984, 540 discloses the preparation of porous collagen dressing sheet materials made by lyophilization; US Pat. No. 6,051,425 discloses a method for producing a collagen laminated sponge for tissue culture consisting of two sponges having different characteristics, and in accordance with the above techniques, human fibroblasts and epidermal cells are initially cultured and hydrated. It has been known that the three-dimensional culture of collagen has resulted in the development of biopsy dermis, so that the clinical application in burn patients and plastic patients can significantly improve wound healing and reduce scars. However, the techniques are commercially available at a very high price because the production cost is high because the animal collagen should be used, and there is a limitation in using as a transplanted tissue due to lack of hardness because of using hydrated collagen gel.

Currently, the ideal method for skin transplantation is to obtain healthy cells from the tissues of the transplanted subjects, combine them with tissue engineering constructs with well-developed microstructured pores, and transplant them into tissue injuries. Regenerates the entire tissue as a cell, and the material used as the tissue engineering structure is to be gradually degraded / absorbed in the body over time, the material for the tissue engineering structure that will enable such ideal skin transplantation at low cost Active research is being done.

On the other hand, chitosan is a kind of polysaccharide that exists in nature. It is a compound obtained by deacetylating chitin contained in the cell walls of microorganisms such as crab, shrimp shell, squid bone, mold and bacteria. It is used in industry. In the past, chitosan was mainly used in the field of wastewater treatment such as flocculants, heavy metal adsorbents, dye wastewater purification agents, and agricultural fields such as soil modifiers, insecticides, plant antiviral agents, and pesticides. The range of food and beverage applications, health and hygiene applications, cosmetic applications, textile-related applications, and pharmaceutical applications is expanding. In particular, the use of chitosan in wound healing agents, artificial skin, pharmacologic materials, blood coagulants, artificial renal membranes, biodegradable surgical sutures, and antimicrobial materials has been reported as a substance that can be used as a medical material since the 1990s.

More specifically, German Patent Nos. 1,906,155 and 1,906,159, which are almost the first patents related to chitin and chitosan-related wound dressings, disclose that pulverized chitin powder has an excellent effect on wound recovery. Japanese Patent No. 3,632,754 and Japanese Patent No. 3,914,413 disclose that chitin promotes wound healing and has a property of being degraded to lysozyme, so that it can be physiologically dissolved. Japanese Patent Laid-Open No. 57-143508 proposes a gauze made from chitin fiber, and only suggests physical properties of the gauze, and Japanese Patent No. 8211258 only shows that the chitin component merely bonds in the process of combining various kinds of materials. It was used only for the purpose of exercising. In Japanese Patent Laid-Open Publication No. 5-92925, chitosan and cotton, chitin and cotton were used for the treatment of burns, indicating that the effect of protecting the wound and relieving pain is excellent. Was dispersed in water at a concentration of 1.5% (w / w), poured onto a polystyrene film and lyophilized to obtain a sponge form. In addition, U. S. Patent No. 4,651, 725 discloses a method of making a wound coating comprising a chitin fiber nonwoven fabric; U. S. Patent No. 4,699, 135 discloses a method for producing a wound dressing consisting of a nonwoven fabric or fibrous sheet of fibrous chitin body; Korean Patent No. 2001-37340 discloses a method for manufacturing a clinical pharmaceutical coating material using high culture chitosan short fibers; Korean Patent No. 2001-19732 discloses a method for producing functional fibers containing chitosan; Korean Patent No. 2000-47330 discloses a nonwoven fabric for wound treatment using chitin and chitosan alginic acid. However, these ordinary gauze dressings are easy to absorb the wound secretion but have no protection against infections such as bacteria from the outside, and keep the wound dry so that the treatment is delayed, and the dressing material adheres to the wound surface and is not easy to exchange. Not only are there problems with neoplastic damage and pain. In addition, because the exudates occur in the early stages of healing, there is a disadvantage that the dressing material must be changed several times a day.

Also as a chitin film, U.S. Patent No. 4,803,078 discloses a method for producing a film laminated wound coating material comprising an expanded polytetrafluoroethylene (PTFE) layer having a chitin layer and pores; Korean Patent No. 2000-66617 discloses a method for producing an amorphous water-soluble chitosan film that dramatically improves coating ability by using high purity chitosan obtained by high molecular weight from chitin. However, these films lack porosity at all, and thus lack of moisture permeability and exudative ability, and due to low permeability, they cannot be used for wounds with many exudates, and if the water swelling condition persists, the dressing material collapses and causes inflammation of normal skin. There is this.

Therefore, in the art, it is excellent in biocompatibility and long in shape retention period, so that it is excellent in improving wound healing, wound healing, sterilization, prevention of scar tissue, and treatment when treating physical trauma including skin damage, surgery and burn. There has been a need for wound dressings having excellent elongation and tensile strength, excellent water absorption, and well-developed uniform size micropores, while having an effect of suppression and wound recovery.

The present inventors have diligently studied to solve the above problems, and as a result, the chitosan structure of a foam dressing obtained by lyophilizing an acidic aqueous solution of chitosan containing glycerol, DMSO, PEG, etc. and adjusting the degree of acetylation, viscosity, and concentration By neutralizing and washing, in its structure, the outer side has little pore to prevent foreign matter and bacteria from invading from the outside, and the inner absorbent layer contains a large number of pores of 50 to 300 μm, and has a effusion absorption capacity and high moisture permeability. The contact layer was provided with a large number of pores of 10 ~ 50㎛ could provide a foam dressing material having a high water absorption.

That is, one aspect of the present invention relates to a composition of iii) freeze-drying an acidic aqueous solution of chitosan containing glycerol, additionally polyethylene glycol (hereinafter referred to as PEG) and / or dimethyl sulfoxide (hereinafter referred to as DMSO) to form chitosan on a foam dressing. Obtaining a structure; Ii) neutralizing / washing the chitosan structure with at least 95% pure ethanol, at least 70% ethanol aqueous solution, at least 50% ethanol aqueous solution and water or buffer to completely remove residual acid; And iii) freeze-drying the neutralized chitosan structure again.

Another aspect of the present invention relates to a method for preparing a neutralized chitosan sponge using a mixed solution of chitosan having different deacetylation degree and / or viscosity as chitosan acidic aqueous solution in step iii) of the method.

Another aspect of the present invention is carried out by dividing the freeze-drying in step iii) preliminary freezing and sublimation drying process, the preliminary freezing is divided into two or more times, at each prefreeze, immediately before freezing chitosan The present invention relates to a method for producing a neutralized chitosan sponge, wherein a chitosan layered structure is obtained by adding a chitosan acid solution to the acid solution and prefreezing and drying the same.

Another aspect of the invention relates to a wound coating or tissue engineering structure using a layered or single phase chitosan foam dressing material produced by the method.

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

The method for producing a foam dressing according to the present invention includes the steps of: i) freeze drying an acidic aqueous solution of chitosan containing glycerol, additionally PEG, DMSO to obtain a chitosan structure on the foam dressing.

Chitosan used in the step is a deacetylated chitin, the viscosity is 2 cps to 800 cps, the degree of deacetylation is used 50 to 99%. The viscosity is a value measured on a Brookfield viscometer at 20 ° C. using a 0.5 mass% chitosan solution in an aqueous 0.5 mass% acetic acid solution.

The acidic aqueous solution of chitosan is prepared by dissolving chitosan at a concentration of 1 to 10% by mass relative to the acidic aqueous solution. Dissolve for 12 to 48 hours for complete dissolution of chitosan. The prepared acidic aqueous solution is left to depressurize or incubate for 3 to 24 hours to completely remove air bubbles in the solution, and completely remove impurities and insoluble residues with filter paper or gauze of 1 to 25 μm.

The acidic aqueous solution of chitosan is prepared by dissolving chitosan in an organic or inorganic acid aqueous solution. Examples of organic or inorganic acids usable in the present invention include acetic acid, hydrochloric acid, lactic acid, pyrionic acid, citric acid, acrylic acid, butyric acid, formic acid, glutamic acid, gluconic acid, glycolic acid, succinic acid, succinic acid, maleic acid, ascorbic acid, tartaric acid And mixed acids obtained by mixing two or more thereof, and the concentration of the organic acid and the inorganic acid aqueous solution is 0.1 to 10 mass% in weight ratio to water.

Glycerol is essentially added to the acidic solution of chitosan, but it is preferable to add 5 to 30% by mass with respect to the acidic aqueous solution. When glycerol is added in less than 5%, it is difficult to expect the formation of fine pores and increase in tensile strength and elongation, and when it exceeds 30%, the concentration of glycerol is too high to form chitosan foam dressing itself.

In addition, PEG or DMSO may be additionally added. Preferably, 0.5 to 10 mass% of PEG or DMSO is added to the acidic aqueous solution by weight, and the molecular weight of PEG used is preferably between 200 and 20,000. According to the research of the present inventors, when using glycerol and PEG as in the present invention, it is possible to obtain a neutralized chitosan foam dressing having excellent mechanical properties in which tensile strength and elongation are dramatically increased through hydrogen bonding with chitosan. If the concentration of PEG is less than 0.5% by mass, the concentration of PEG is so low that it is difficult to expect an increase in tensile strength and elongation through hydrogen bonding. If it exceeds 10% by mass, the concentration of PEG is so high that the effect of chitosan foam dressing cannot be expected. . DMSO also affects the freezing point, resulting in a multi-layered neutralizing chitosan foam dressing with finer pores. More specifically, it is prepared by adding DMSO in an amount of 0.5 to 10 mass% by weight of an acid aqueous solution. In this case, if the concentration of DMSO is less than 0.5% by mass, the concentration is too low to be expected due to the freezing point due to DMSO. If the concentration exceeds 10% by mass, the concentration of DMSO is too high, so that chitosan foam dressing itself is not formed.

The prepared chitosan acid aqueous solution is placed in a dish of a predetermined shape and size, and freeze-dried to prepare a sponge-like structure in which pores of a predetermined size are formed.

Freeze drying is a method of freezing the material and then drying it by sublimation with gaseous vapor without drying the liquid state in a high vacuum apparatus, and a much higher quality product can be obtained than a general drying method. As moisture is removed from the dried product, the dried product is characterized by having a light sponge or foam form and is a drying method to obtain a high-quality product currently used for drying foods, pharmaceuticals, and microorganisms. In the present invention, the lyophilization is preferably performed by dividing the process of prefreezing and sublimation drying.

When preliminary freezing, the freezing temperature has a great effect on the quality of the dried product, so careful attention is required for its control. In the present invention, the preliminary freezing is performed at minus 140 to minus 160 ° C using minus 10 ° C to minus 80 ° C or liquid nitrogen. Freeze treatment. Sublimation drying is a process of removing the organic solvent present in the chitosan solution. At this time, water is gradually removed to the upper portion of the freezing layer, leaving the chitosan foam dressing material, and the sublimation screen is lowered, and the freezing layer disappears eventually, and the chitosan foam dressing material is removed. Obtained. In lyophilization, in the present invention, a sponge-like chitosan structure may be prepared by vacuum drying a chitosan solution at a temperature of 10 ° C. to 30 ° C. under a vacuum degree of 10 mmHg or less.

In a preferred embodiment of the present invention, the preliminary freezing in step iii) is carried out in two or more times, and at each preliminary freezing, an additional aqueous chitosan solution is added to the preliminary freezing chitosan aqueous solution. By drying it as a whole, a sponge-like chitosan layered structure can be obtained. At this time, each pre-freezing can be performed by varying the freezing temperature and time, when the pre-freezing temperature is minus 10 ℃ to minus 80 ℃ for 2 to 24 hours, minus 80 ℃ to minus 160 ℃ If performed for 1 to 12 hours. In obtaining a layered sponge by a plurality of preliminary results, the additional aqueous chitosan solution added in step iii) is the same aqueous solution as the previously pre-frozen chitosan solution, or a chitosan solution with different concentrations, or A preliminarily frozen aqueous chitosan acid solution and an acid aqueous solution of the same or different concentration of chitosan with different viscosity and / or deacetylation degrees are used.

In the step iii) of the present invention, an acidic aqueous solution of chitosan containing glycerol prepared by mixing two or more kinds of chitosans having different molecular weights (or viscosities) and / or deacetylation degrees may be used. When mixed chitosan with different deacetylation degree is used, 1) Multi-layered neutralizing chitosan foam dressing made of low molecular weight with excellent antimicrobial activity but low mechanical strength can increase mechanical properties while maintaining antimicrobial activity. 2 By using chitosan and chitin with different deacetylation degree together, it has the effect of raising / complementing both advantages (for example, having high solubility and excellent antibacterial property), and 3) multi-layer having desired various physical properties. Structure neutralizing chitosan foam dressing can be obtained. More specifically, within the range of 2 cps to 800 cps viscosity and the deacetylation degree of 50% to 99%, chitosan having a predetermined viscosity and deacetylation degree, and the chitosan and the viscosity and deacetylation degree are different, respectively, An acidic aqueous solution of chitosan may be prepared by mixing one or two or more chitosans having the same viscosity and different degrees of deacetylation, or having the same deacetylation degree and different viscosity.

Conventional chitosan-based films have no pores or are too small in size, lack of moisture permeability and exudation ability, and are not available for wounds with high exudation due to low water permeability. There are disadvantages such as causing. On the other hand, nonwoven fabrics using fibers, ie gauze dressings, are easy to absorb the secretions of the wound, but they do not have protection against infections such as bacteria from the outside and keep the wounds dry to delay the treatment. Not only does not elute the exchange by attaching to it, there are problems involving neoplastic damage and pain. In addition, because the exudates occur in the early stages of healing, there is a disadvantage that the dressing material must be changed several times a day. However, when using the method according to the present invention, the tensile strength and elongation rate is significantly increased, and chitosan foam dressing material having uniform micropores can be prepared, which prevents leakage of water from the body, absorption of exudates and various germs from the outside. In addition to excellent intrusion and infection prevention effect, the air flow through the foam dressing has the advantage of helping the healing of wounds and differentiation and growth of cells.

In step ii) of the preparation method according to the invention, the chitosan structure obtained in step iii) is a) at least 95% pure ethanol, b) at least 70% ethanol aqueous solution, c) at least 50% ethanol aqueous solution, and d) water or Neutralization and washing in turn with buffer to completely remove residual acid. The chitosan structure on the foam dressing obtained in step iii) contains the organic acid as it is in the foam dressing, so that the remaining organic acid is completely removed in this step. The prior art in this case is neutralized with basic solution and then washed with water or buffer, but according to the study of the present inventors, upon use of such basic solution, the foam dressing obtained is contracted or severely warped as a whole while contacting the basic solution. This happens and the original form cannot be maintained as it is, or a significant decrease in strength is caused. In order to recognize and effectively solve the above problem, the present inventors neutralize and wash the chitosan foam dressing in the order of pure ethanol, an aqueous ethanol solution (ie, a mixture of water and ethanol) and water or a buffer to completely remove residual acid. It was. In the process according to the invention, the residual organic acid is completely removed step by step using ethanol, a mixture of water and ethanol, water or a buffer in turn, without the use of a basic solution, so that no shrinkage or distortion of the foam dressing occurs and no freezing occurs. It is possible to maintain the form as it is dried, not only to obtain a well-developed foam dressing material fine pores, but also to neutralize, cleaning process sterilization is more advantageous.

The method according to the invention comprises the steps of iii) lyophilizing the neutralized chitosan structure again. Freeze drying of this step is as described above. Through this step, it is possible to obtain a neutralized chitosan structure in which micropores having a predetermined size are uniformly distributed.

The neutralizing chitosan structure obtained through the above steps is composed of a multi-layered structure as well as antimicrobial activity, immune activity enhancement, and biocompatibility, which are inherent in chitosan, and prevents invasion of bacteria and foreign substances, and has characteristics of high moisture permeability and high absorption. The scar after treatment was minimized, and in particular, by including glycerol and additionally PEG and DMSO in the acidic aqueous solution of chitosan, the elongation rate and tensile strength were significantly increased than those produced by chitosan alone, and the fine pores of uniform size were better developed. Since the wound healing rate can be used as a wound coating material superior to conventional products.

Preferably, the chitosan foam dressing material of the present invention is composed of an outer layer, an inner absorbent layer and a wound surface contact layer, and has a thickness of 0.1 to 20 mm, the inner absorbent layer is 50 to 300 µm thick, and the wound surface contact layer is 10 to 50 µm. It is preferable that it is the thickness of.

Hereinafter, the structure and effect of the present invention will be described in more detail with specific examples and comparative examples, but these examples are only intended to more clearly understand the present invention, and are not intended to limit the scope of the present invention.

EXAMPLE

Measure the physical properties as follows

(1) Mechanical Properties (tensile strength, elongation)

It measured by the tensile tester (Instron 5565) based on JIS-K-6401.

(2) Absorbance%

The chitosan foam dressing agent was cut into a size of 5 cm × 5 cm, dried in an oven at 50 ° C. for 24 hours, the initial weight (A) was measured, immersed in distilled water for 24 hours, taken out to remove moisture from the surface, and then weighed (B ) Was calculated using the following formula.

Absorbance% = (B-A) / A × 100

(3) pore size

Scanning electron microscopy is used to measure the pore size of both surfaces and cross sections of the chitosan foam dressing material.

Example 1

Using a 1.2% aqueous acetic acid solution containing 5% glycerol, a viscosity of 11 cps (prepared 0.5 wt% chitosan solution of 0.5 wt% acetic acid and measured at 20 DEG C with a Brookfield viscometer) and a deacetylation degree of chitosan of 98% An aqueous solution of 3 w / w% was prepared. The obtained solution was filtered to remove the insoluble substance, and then 60 g of the solution was placed in a plastic dish of 12 × 12 cm and left at room temperature for 24 hours to completely remove air in the solution. The solution was preliminarily frozen for 24 hours in an ultra-low temperature freezer at minus 70 ° C., followed by sublimation drying at minus 20 ° C. for 48 hours to obtain a chitosan structure of foam dressing. The obtained chitosan structure was washed two or more times with 1 L of 95% ethanol, again twice or more with 1 L of 70% ethanol, and washed twice or more with 1 L of 50% ethanol, and then several times with 1 L of distilled water. Washed. The washed chitosan structure was frozen again in an ultra-low temperature freezer at -70 ° C for 24 hours and then dried at -20 ° C for 24 hours to uniformly distribute micropores of a uniform size. Ash was prepared.

Example 2

The same procedure as in Example 1 was conducted except that an aqueous 3% w / w% solution of chitosan with a viscosity of 11 cps and a deacetylation degree of 98% was prepared using an aqueous 1.2% acetic acid solution containing 10% glycerol. The neutralized chitosan foam dressing material of the multilayer structure was prepared.

Example 3

The same procedure as in Example 1 was conducted except that an aqueous solution of 4 w / w% of chitosan having a viscosity of 11 cps and a deacetylation degree of 98% was prepared using an aqueous 1.2% acetic acid solution containing 15% of glycerol. The neutralized chitosan foam dressing material of the multilayer structure was prepared.

Example 4

The same procedure as in Example 1 was conducted except that an aqueous solution of 5 w / w% of chitosan having a viscosity of 11 cps and a deacetylation degree of 98% was prepared using an aqueous 1.2% acetic acid solution containing 10% of glycerol. The neutralized chitosan foam dressing material of the multilayer structure was prepared.

Example 5

A neutralized chitosan foam dressing material having a multilayer structure was prepared in the same manner as in Example 1, except that PEG 1% having a molecular weight of 10,000 was added.

Example 6

A neutralized chitosan foam dressing material having a multilayer structure was prepared in the same manner as in Example 1, except that PEG 3% having a molecular weight of 300 was added.

Example 7

A neutralized chitosan foam dressing material having a multilayer structure was prepared in the same manner as in Example 1, except that 1% DMSO was added.

Example 8

A neutralized chitosan foam dressing material having a multilayer structure was prepared in the same manner as in Example 1, except that 2% DMSO and PEG 2% having a molecular weight of 10,000 was added.

Example 9

Viscosity 11 cps (prepared 0.5 wt% chitosan solution of 0.5 wt% acetic acid and measured at 20 ° C. with Brookfield viscometer), 1.2% acetic acid containing 10% glycerol with chitosan 1 as chitosan with 98% deacetylation degree An aqueous solution was used to prepare 3 w / w% chitosan 1 acidic aqueous solution. Separately, viscosity 212 cps (prepared 0.5 wt% chitosan solution of 0.5 wt% acetic acid and measured at 20 ° C. with Brookfield viscometer), chitosan with deacetylation degree of 98% as chitosan 2, 1.2 containing 10% glycerol 3 w / w% chitosan diacid aqueous solution was prepared using% acetic acid aqueous solution. The two solutions were mixed at a volume ratio of 1: 1, and the obtained solution was filtered to remove insoluble matters. Then, 50 g of the solution was placed in a plastic dish of 12 × 12 cm and left at room temperature for 24 hours to completely remove air in the solution. It was. The solution was preliminarily frozen in a cryogenic freezer at minus 70 ° C. for 24 hours and then sublimed and dried at minus 20 ° C. for 48 hours to obtain a chitosan structure in a foam dressing. The obtained chitosan structure was washed two or more times with 1 L of 95% ethanol, again twice or more with 1 L of 70% ethanol, and washed two times or more with 1 L of 50% ethanol, and then several times with 1 L of distilled water. Washed. The washed chitosan structure was frozen again in an ultra-low temperature freezer at -70 ° C for 24 hours and then dried at minus 20 ° C for 24 hours to uniformly distribute micropores of a uniform size. Ash was prepared.

Comparative Example 1

To 97 g of 1 wt% aqueous acetic acid solution was added 3 g of chitosan having a viscosity of 1446 cps and a degree of deacetylation of 94%, and dissolved by stirring using a stirrer to prepare a transparent solution. The prepared chitosan solution was aged at 4 ° C. for 12 hours. The aged chitosan solution was formed into a 300 mm thick film using a film maker capable of adjusting the thickness on the Teflon film. The formed chitosan film was dried at room temperature for 12 hours to obtain a water-soluble chitosan film having the thickness required above.

Comparative Example 2

Quantitative chitosan (deacetylation degree: 84%, molecular weight: 400,000) was completely dissolved in a 1v / v% formic acid aqueous solution to give a solution of 0.5w / w%. The solution was depressurized in a sterile hood to remove air bubbles in the solution. 20 ml of the solution was placed in a plastic culture dish having a diameter of 100 mm, and allowed to stand for 48 hours in an ultra low temperature of -70 deg. This freezing solution was freeze-dried for at least 72 hours to obtain chitosan sponge artificial dermis. The obtained chitosan sponge artificial dermis was washed 6 times or more with an aqueous solution of 2.0 M ammonium hydroxide which is an alkaline solution for neutralization. In this way, a sponge-like dermis having a thickness of about 2 mm was prepared, but the sponge was completely shrunk and twisted to obtain a sponge of a desired shape.

Table 1 shows the results of evaluating the physical properties of the chitosan foam dressing material prepared in Examples 1 to 9 and Comparative Examples 1 to 2.

division Tensile Strength (MPa) Elongation (%) Absorbance (%) Example 1 0.98 38 1,240 Example 2 1.10 42 1,340 Example 3 1.22 49 1,370 Example 4 1.08 51 1,480 Example 5 1.29 50 1,390 Example 6 1.31 47 1,350 Example 7 0.99 46 1,370 Example 8 1.11 47 1,310 Example 9 1.08 44 1,275 Comparative Example 1 0.48 3 220 Comparative Example 2 0.35 6 568

The multi-layered closed foam dressing material using chitosan according to the present invention has improved mechanical properties by significantly increasing tensile strength and elongation rate compared to the prior art using chitosan having a fiber, film, or powder form, and having a predetermined uniform size. Because of its micropores, the surface area is widened to improve absorption, and the excellent air permeability and the ability to collect and remove secretions discharged from the wound area can be improved, thus minimizing scars after treatment for wound healing and existing wound healing speed. It is faster than the product.

In addition, when two or more kinds of deacetylation and different viscosity of chitosan are used, the characteristics of chitosan can be maximized, and final wound dressings and foam dressings are prepared by using ethanol, ethanol aqueous solution and water or buffer instead of basic solution in the washing and neutralizing step. It can effectively prevent shrinkage or torsion, which is a problem of ashes.

Claims (12)

Iii) freeze drying an acidic aqueous solution of chitosan, including glycerol, to obtain a chitosan structure on the foam dressing; Ii) neutralizing and washing the chitosan structure in order of a) at least 95% pure ethanol, b) at least 70% ethanol aqueous solution, c) at least 50% ethanol aqueous solution, and d) water or buffer solution to completely remove residual acid. step; And Iii) a method of producing a chitosan foam dressing material, which comprises freeze-drying the neutralized chitosan structure again. The chitosan form dressing material according to claim 1, further comprising polyethylene glycol (PEG) and / or dimethyl sulfoxide (DMSO) in the chitosan acidic aqueous solution. The chitosan acidic aqueous solution of claim 1, wherein the chitosan acidic aqueous solution is a mixed solution of chitosan having different deacetylation degree and / or viscosity. [Claim 2] The chitosan foam dressing material of claim 1, wherein the chitosan uses chitosan within a range of 2 cps to 800 cps viscosity and a deacetylation degree of 50% to 99% based on 1 to 10% by weight of the total acidic aqueous solution. Manufacturing method. The method for producing a chitosan foam dressing material according to claim 1, wherein glycerol is added in an amount of 5 to 30% by mass in the acid aqueous solution. The method for producing a chitosan foam dressing material according to claim 2, wherein the PEG has a molecular weight of 200 to 20,000 and a weight ratio to an aqueous acid solution is 0.5 to 10 mass%. The method for producing a chitosan foam dressing material according to claim 2, wherein DMSO is used in an amount of 0.5 to 10 mass% in the aqueous acid solution. According to claim 1, wherein step iii) freeze-drying is carried out divided into a pre-freezing and sublimation drying process, the preliminary freezing result is minus 10 ℃ to minus 80 ℃, or minus 140 ℃ to minus 180 ℃ using liquid nitrogen And, the freeze-drying process is a method for producing a chitosan foam dressing, characterized in that carried out by vacuum drying at minus 20 ℃ to 30 ℃. 9. The preliminary freezing chitosan solution of claim 8, wherein the preliminary freezing in the step iii) is carried out in two or more times, and at each prefreezing, the freezing temperature and time are the same or different. A method of producing a chitosan foam dressing material, further comprising pre-freezing by adding an aqueous chitosan acid solution and drying it to obtain a sponge-like chitosan layered structure. The chitosan foam dressing material of claim 1, wherein the chitosan foam dressing material is a chitosan foam dressing material including an outer layer, a wound surface contact layer, and an inner absorption layer, and has a thickness of 0.1 to 20 mm, and the wound surface contact layer includes pores having a diameter of 10 to 50 µm. And the inner absorbent layer comprises pores having a diameter of 50 to 300 µm. delete delete

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