KR20030002224A - Barrier membrance for guided tissue regeneration and the preparation thereof - Google Patents

Abstract

PURPOSE: Provided is a shielding membrane for induction of tissue regeneration which has an excellent effect of shielding invasion of epithelial cells and bonding tissues, help a bone tissue to grow and can be conveniently designed in an operation, and a method for producing the same. CONSTITUTION: The shielding membrane comprises two sheets of chitosan non-woven fabric and a porous bio-degradable polymer membrane disposed therebetween. The bio-degradable polymer is formed of bio-degradable polyester polymer such as polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer and polycaprolactone. The bio-degradable polymer membrane has a thickness of 0.01 to 10 mm. The chitosan non-woven fabric includes a foreign substrate ingredient to improve bio-compatibility, a ceramic ingredient to improve the mechanical strength and bone tissue regeneration or a mixture thereof.

Description

Barrier membrance for guided tissue regeneration and the preparation

The present invention relates to a membrane for inducing tissue regeneration for inducing regeneration of damaged alveolar bone and a method of manufacturing the same, and more specifically, a membrane for inducing tissue regeneration in which a porous biodegradable polymer membrane having micropores formed between chitosan nonwoven fabrics and sandwiches thereof is prepared. It is about a method.

In the treatment of alveolar bone damage caused by periodontal disease, the periodontal tissue may not be regenerated even if the periodontal disease is suppressed, and even if new bone is formed, the bone may be irregularly formed or replaced by gingival connective tissue, thereby losing the function of the periodontal tissue. May be In other words, the gingival connective tissue in the damaged area regenerates faster than bone tissue or periodontal ligament tissue and penetrates into these tissues. Therefore, normal regeneration of the alveolar bone and periodontal ligament tissue does not proceed smoothly, and anatomical deformation and loss of function are caused. Surgery is required.

Alveolar bone regeneration currently being performed to solve this problem is a method of inducing bone formation by filling the damaged area by autografting (autografting). Another method is to use the bones of humans or animals from which immunogenicity has been removed as an artificial bone substitute, or to use commercially available hydroxyapatite.

Recently, attention has been focused on the bone regeneration effect of demineralized bone powder and bone morphogenic protein obtained from it. In addition, various methods have been tested to prove bone tissue regeneration ability, It is not widely applied to them. Accordingly, in the regeneration of periodontal tissues, new artificial membranes have been introduced into tissues to promote the healing of periodontal tissues and to restore them to complete periodontal tissues, while improving the results of bone grafts and inducing the production of new alveolar bones. .

An example of a technique for surgically inserting a shield into a damaged area to improve recovery and regeneration of a specific tissue is a general tissue regeneration induction shield having a natural or synthetic latex or polytetrafluoroethylene as its material. In addition, the tissue regeneration induction membrane has a problem in that the above-described natural or synthetic latex (latex) or polytetrafluoroethylene is non-degradable, so that a secondary removal surgery is required to remove it.

Republic of Korea Publication No. 2000-73589 has a fiber thickness of 0.1 ㎛ ~ 0.001 ㎛ and biodegradable nonwoven fabric of one side produced by melt spinning, and a fiber thickness of 0.1 ㎛ ~ 400 ㎛ biodegradable polymer produced by melt spinning Disclosed are a membrane for inducing tissue regeneration for treating periodontal disease laminated and compressed. However, the above described tissue regeneration induction shielding membrane has a problem in manufacturing process that should be melt spinning and solution spinning, and the problem that the drug for treating periodontal disease is not effective enough by being incorporated into the space (or matrix of nonwoven fabric) formed in the nonwoven fabric. It also has a problem that it can not exhibit sufficient mechanical strength.

Accordingly, the present inventors have studied intensively to prepare an improved tissue regeneration induction barrier membrane having sufficient mechanical strength and useful for the treatment of alveolar bone regeneration.As a result, a porous biodegradable polymer membrane in which micropores are formed between chitosan nonwoven fabrics is sandwiched in tissue regeneration induction membrane. The present invention has been found to be able to improve the above problems.

Accordingly, it is an object of the present invention to provide a membrane for inducing tissue regeneration in which a porous biodegradable polymer membrane having micropores formed between chitosan nonwoven fabrics is sandwiched.

Still another object of the present invention is to provide a method of manufacturing the membrane for inducing tissue regeneration.

1 is a surface of the tissue regeneration induction shielding membrane of the present invention observed with a differential scanning microscope,

FIG. 2 is a cross-sectional view of a sandwiched biodegradable polymer membrane between tissue inducing shields of the present invention observed with a differential scanning microscope,

Figure 3a is a result of attaching the osteoblasts of the tissue-induced shielding membrane of the present invention observed with a differential scanning microscope for 1 day,

Figure 3b is a result of attaching the osteoblasts of the tissue regeneration induction shielding membrane of the present invention observed with a differential scanning microscope for 7 days.

<Explanation of symbols on main parts of the drawings>

1: biodegradable polymer membrane 2: chitosan nonwoven fabric

In order to achieve the above object, the present invention provides a membrane for inducing tissue regeneration in which a porous biodegradable polymer membrane sandwiched with micropores is formed between chitosan nonwoven fabrics.

The membrane for inducing tissue regeneration according to the present invention ensures selective cell growth induction function of the membrane by the micropores formed in the biodegradable polymer membrane, and prevents regeneration-inhibiting cells, and obtains the angiogenic effect. Neutralizes the acid produced by hydrolysis of the polymer used in the polymer membrane to reduce the inflammatory reaction and tissue toxicity, and by sequentially laminating the nonwoven fabric, the polymer membrane, and the nonwoven fabric, the mechanical strength of the membrane for inducing tissue regeneration is sufficiently improved. You can.

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

1Is the surface of the tissue regeneration induction shielding membrane of the present invention observed with a differential scanning microscope, more specifically2in The membrane for inducing tissue regeneration of the present invention observed by a differential scanning microscope shows a cross-sectional view of a biodegradable polymer membrane in which a biodegradable polymer membrane 1 is sandwiched between chitosan nonwoven fabrics 2. It is possible to confirm the porous structure of the micropores of 2 to 10 μm formed inside the biodegradable polymer membrane 1 and have sufficient pores to block the infiltrating tissue cells, which are regeneration inhibitory cells of about 10 to 30 μm, invading. to be. In addition, the formed micropores thus provide an effect to ensure selective cell growth induction of the barrier membrane, to prevent regeneration while blocking the regeneration cells. The formation of micropores is possible by the use of a mixed solvent, which will be described later. If necessary, chitosan nonwoven fabric, biodegradable polymer membrane, chitosan nonwoven fabric, biodegradable polymer membrane, chitosan nonwoven fabric may be further laminated in this order. In addition, the tissue regeneration induction shielding membrane of the present invention has an advantage that the mechanical strength of the tissue regeneration induction shielding membrane can be sufficiently improved by sequentially stacking the nonwoven fabric, the polymer membrane, and the nonwoven fabric.

Biodegradable polymer materials that can be used in the preparation of the biodegradable polymer membrane of the present invention are polyesters, and examples thereof include polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, and polycaprolactone. Polylactic acid is the first polymer used together with polyglycolic acid as an in vivo degradable implant, which has been used primarily in the manufacture of matrixes or surgical materials for drug delivery systems. Antimicrobial agents, antagonists, contraceptives, anticancer drugs, etc. in the delivery of the body in the form of a fine, implanted subcutaneous or intravenous injection to the animal has proved its application. The thickness of the biodegradable polymer membrane is usually 0.01 to 10 mm, preferably 0.05 to 3 mm to ensure sufficient mechanical strength and induce effective tissue regeneration.

Chitosan used in the production of nonwovens is biodegradable and contains amine groups in the tissues, so that lactic acid, glycols, and the like when polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymers, etc. used in biodegradable polymer membranes are hydrolyzed in vivo If acid is produced, such as acid, the pH around the polymer formulation decreases, causing inflammatory reactions and histotoxicity. Therefore, if the blood vessels are incapacitated or metabolic, the tissues are less capable of removing acid-degrading products. The potential for toxic effects is greater, but can be neutralized to prevent side effects.

In addition, the structure similar to the glycosaminoglycan of the extracellular matrix has the advantage of excellent tissue compatibility.

The fiber thickness of the chitosan nonwoven fabric according to the present invention is not particularly limited, and can be freely within, for example, 0.001 to 400 µm. Fiber thickness may vary depending on the nature of the biodegradable polymer used and the like, but generally depends greatly on the spinning method of the nonwoven fabric. For example, in the case of solution spinning, a nonwoven fabric having a diameter in the range of 0.1 µm to 400 µm is obtained, but by spinning and spinning a high voltage during spinning, the thickness of the fiber can be made extremely fine to about 0.001 µm.

The chitosan nonwovens of the present invention preferably further comprise an in vitro matrix component that enhances biocompatibility and / or a ceramic component that enhances mechanical strength and bone tissue regeneration effects. Examples of ceramic components include tricalcium phosphate (TCP) or calcium metaphosphate.

Usually, drugs for treating periodontal disease are included in the biodegradable polymer membrane. However, the present invention is not necessarily limited thereto, and may be embedded in a matrix formed by the nonwoven fabric. Drugs for treating periodontal disease include flubiprofen, ibuprofen, indomethacin, naproxen, mephenamic acid, tetracycline, minocycline, oxytetracycline, metronidazole, platelet-derived growth factor, and insulin-like growth factor. , Epidermal growth factor, tumor growth factor or mixtures thereof, and these are usually added in an amount of 5 to 20% by weight based on the weight of the polymer.

The biodegradable polymeric membranes and / or chitosan nonwovens described above may further comprise plasticizers, surfactants commonly used in the art, and their use is widely known in the art. For example, refer to Korean Patent No. 180585 filed by the present applicant.

The present invention also relates to a method for producing a polymer membrane for inducing tissue regeneration, wherein the method comprises spinning a biodegradable polymer material in a spinning apparatus to obtain a chitosan nonwoven fabric, and a main solvent and a nonsolvent of a biodegradable polymer material on the surface of the obtained nonwoven fabric. And applying a mixed solution of to form a biodegradable polymer membrane having micropores, and laminating and pressing the chitosan nonwoven fabric obtained above on the surface of the biodegradable polymer membrane, followed by drying. In the present specification, the main solvent refers to a solvent having a solubility of 0.01 g / ml or more, preferably 0.05 to 0.2 g / ml, and a boiling point of 30 to 70 ° C. with respect to the biodegradable polymer used in the preparation of the biodegradable polymer membrane. As used herein, the subsolvent refers to a solvent having a solubility of 0.4 g / ml or less, preferably 0.2 to 0.4 g / ml, and a boiling point of 50 to 90 ° C with respect to the biodegradable polymer.

Micropores may be formed in the biodegradable polymer membrane by dissolving the biodegradable polymer material using a mixed solvent of the main solvent and the subsolvent. More specifically, after being applied as a mixed solution, the main solvent having high solubility and low boiling point in the biodegradable polymer material is evaporated first, and the proportion of the low solubility and high boiling point solvent in the biodegradable polymer is relatively increased. As a result, the dissolving power of the biodegradable polymer is lowered and the subsolvent and the biodegradable polymer are separated. Therefore, after the subsolvent is completely evaporated, micropores are formed at the site where the subsolvent was present. Examples of the solvent that can be used as the main solvent include methylene chloride, and examples of the solvent that can be used as the subsolvent include ethyl acetate, dioxane and chloroform. The type of main solvent and subsolvent may vary depending on the type of biodegradable polymer used, and one of ordinary skill in the art will appropriately select it.

The spinning method for forming the nonwoven fabric is not particularly limited, and solution spinning, melt spinning and melt brown may be employed. When solution spinning is used in the above method, it may further include an in vitro matrix component for improving biocompatibility and / or a ceramic component for improving mechanical strength and bone tissue regeneration ability (eg, TCP, calcium metaphosphate, etc.). More preferred. Solvents capable of dissolving chitosan during solution spinning include, but are not limited to, lactic acid, acetic acid and hydrochloric acid, and the choice of solvent may be appropriately modified by those skilled in the art. The biodegradable polymer fibers released from the spinning device are solidified while passing through the coagulation bath and washed while passing through the washing bath to produce a chitosan nonwoven fabric. The coagulation solution on the preparation method is a polymer selected from a solvent containing a mixed solvent of potassium hydroxide and ethylene glycol, a mixed solvent of sodium hydroxide and ethylene glycol, potassium hydroxide solution, sodium hydroxide solution, ethanol, methanol and acetone It may be selected differently depending on the type. In addition, the solution used in the washing tank is prepared in distilled water that is selected from methanol and ethanol.

In the biodegradable polymer solution used in the preparation of the biodegradable polymer membrane, a plasticizer may also be added to impart plasticity to the shielding membrane. Plasticizers that can be used include diethyl terephthalate, polyethylene glycol, glycerin or mixtures thereof, and are added and dispersed in an amount of 10 to 30% by weight based on the weight of the polymer used.

In addition, the hydrophilic material and the surfactant may be added to the polymer solution to enhance the water affinity of the shielding film. The hydrophilic material includes hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), sodium chloride, glycerin, chitosan, alginate, or mixtures thereof, and may contain 10 to 20% by weight based on the weight of the polymer used. It is preferred to be added to the polymer solution in an amount. In addition, the surfactants used to uniformly disperse these additives in the polymer solution include polyethylene-polyoxypropylene block copolymers (product name: Pluronics or Poloxamers), and the polymer weight is 5 to It is preferred to add in an amount of 15% by weight.

It is preferable to treat the shielding film produced by applying the prepared biodegradable polymer solution to the chitosan nonwoven fabric with a non-solvent in order to increase its micropore generating ability. The nonsolvent treatment can be performed by immersing the shielding membrane in a nonsolvent such as methanol, distilled water or ethyl acetate for 12 to 24 hours or by placing it in a saturated water bath and leaving it for 12 to 24 hours before taking it out and drying it. have. The increase of micropore generating ability by nonsolvent treatment is based on the principle of porosity formation by phase transition due to the difference in solubility between the main solvent and the nonsolvent.

The tissue regeneration inducing membrane of the present invention prepared above is inserted into or overlaid on the damaged alveolar bone or implanted jaw area, and then fixed to the root with a surgical biodegradable suture or secured to bone tissue using a biocompatible adhesive. When attached, the bone tissue that requires induced regeneration is located on the inner surface of the shielding membrane and the connective tissue or epithelial tissue is directly contacted and covered on the outer surface.

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

However, the following examples are merely to illustrate the content of the present invention is not limited to the scope of the present invention.

Preparation Example 1 Chitosan Nonwoven Fabric

Chitosan having a molecular weight of 200,000 was dissolved in a 1% acetic acid solution to prepare a 4% chitosan solution. At this time, a spinneret having 30 spinners and a diameter of 0.2 mm spinnerets of the solution spinning device was used, and the pressure was 0.6 to 1.2 atm and spun at a spinning speed of 5 to 6 m / min. The solution of the coagulation bath was prepared by adding 400 g of potassium hydroxide to 400 g of ice, and the solution of the washing bath was prepared by adding 400 g of distilled water to 1 kg of ethylene glycol. The chitosan fibers released from the solution spinning device were solidified while passing through the coagulation bath. It was washed while passing through the washing bath to prepare a chitosan nonwoven fabric consisting of chitosan fibers. At this time, the fiber of the chitosan nonwoven fabric has an average thickness of 50 µm.

Production Example 2 Manufacture of Chitosan-TCP Nonwoven Fabric

In the preparation method of Preparation Example 1, chitosan having a molecular weight of 200,000 was dissolved in a 1% acetic acid solution, and TCP 50% was added to the 4% chitosan solution. A chitosan nonwoven fabric was prepared, and the thickness of the chitosan-TCP fibers prepared by the spinning method was 60 μm on average.

Example 1 Fabrication of Tissue Induced Shield Membrane with L-polylactic Acid Biodegradable Polymer Membrane Between Chitosan Nonwoven Fabrics

6 mL of methylene chloride and 3 mL of ethyl acetate were added to 1 g of L-polylactic acid having a molecular weight of 370,000, and 0.3 mL of Span 80 as a surfactant was added thereto to prepare a uniform polymer solution by stirring.

The solution was applied to one side of the chitosan nonwoven fabric prepared in Preparation Example 1, and further laminated on the chitosan nonwoven fabric prepared in Preparation Example 1 thereon, followed by drying and vacuum drying at room temperature for 24 hours, followed by L-polylactic acid. A membrane for inducing tissue regeneration in which the biodegradable polymer membrane was sandwiched was fabricated.

As shown in FIG. 2 , as a result of observing the characteristics of the prepared tissue regeneration inducing membrane with a differential scanning microscope, the surface of the membrane showed a chitosan nonwoven layer, and a chitosan nonwoven layer was observed on both sides of the inside of the membrane. In between, a biodegradable polymer membrane of L-polylactic acid was observed.

<Example 2> Fabrication of the membrane for inducing tissue regeneration in which a biodegradable polymer membrane of polycaprolactone was sandwiched between chitosan nonwoven fabrics

6 mL of methylene chloride and 3 mL of ethyl acetate were added to 1 g of polycaprolactone having a molecular weight of 130,000, 0.3 mL of Span 80 as a surfactant was added thereto, and a uniform polymer solution was prepared by stirring.

The solution was applied to one side of the chitosan nonwoven fabric prepared in Preparation Example 1, and the chitosan nonwoven fabric prepared in Preparation Example 1 was further laminated thereon, followed by compression and drying at room temperature for 24 hours, followed by drying and vacuum drying for polycapro. A membrane for inducing tissue regeneration in which a biodegradable polymer membrane of lactone was sandwiched was fabricated.

<Example 3> Preparation of a shield membrane for inducing tissue regeneration in which a biodegradable polymer membrane of polylactic acid-glycolic acid copolymer was sandwiched between chitosan nonwoven fabrics

6 mL of methylene chloride and 3 mL of ethyl acetate were added to 1 g of a polylactic acid-glycolic acid copolymer having a molecular weight of 130,000, and 0.3 mL of Span 80 as a surfactant was added thereto to prepare a uniform polymer solution by stirring. . The solution was applied to one side of the produced chitosan nonwoven fabric, and the chitosan nonwoven fabric prepared above was laminated thereon, pressed, dried at room temperature for 24 hours, and then vacuum dried to prepare a porous shielding membrane.

Example 4 Fabrication of Tissue Induced Shielding Film with Biodegradable Polymeric Membrane of L-Polylactic Acid Between Chitosan-TCP Nonwoven Fabric

6 mL of methylene chloride and 3 mL of ethyl acetate were added to 1 g of L-polylactic acid having a molecular weight of 370,000, and 0.3 mL of Span 80 as a surfactant was added thereto to prepare a uniform polymer solution by stirring.

The solution was applied to one side of the chitosan-TCP chitosan nonwoven fabric prepared in Preparation Example 2, and the chitosan-TCP chitosan nonwoven fabric prepared in Preparation Example 2 was further laminated thereon, followed by compression and drying for 24 hours at room temperature, followed by vacuum drying. Through the production of a shield membrane for inducing tissue regeneration.

Hereinafter, the characteristics of the membrane for inducing tissue regeneration of the present invention were tested.

Experimental Example 1 Mechanical Strength Measurement

Tensile strength was measured to determine the mechanical strength of the membrane for inducing tissue regeneration of the present invention. Instron (trade name: Instron 8511; Instron corp., USA) was used for the measurement of the tensile strength, and the results of using a 500 N load cell at a speed of 1 mm / min are shown in Table 1 below.

Tensile Strength Measurement Tensile strength (kPa) Example 1 3541.67 Example 2 3125.00 Example 3 3245.27 Example 4 4375.00 Nonwoven fabric consisting of chitosan only 1670 ± 797

As shown in the results of Table 1 , the resulting nonwoven fabric consisting of chitosan only has a tensile strength of 1670 ± 797 kPa, while the porous biodegradable polymer membrane having micropores formed between the chitosan nonwoven fabric of the present invention induces tissue regeneration. For the shielding membrane, the mechanical strength was improved to 3680 ± 636 kPa.

Experimental Example 2 Osteoblast Adhesion Test of Tissue Induction Shield Membrane

In order to effectively cover the damaged area of the membrane, adhesion of cells around the membrane is essential and adhesion by bone cells in bone injury is also essential in effective guided tissue.

Osteoblasts were counted with a hematocytometer and added to a complete media (DMEM supplemented with 10% FBS, 8 μg / ml gentamycine, 10 mM Na β-glycerol phosphate, 50 μg / ml L-ascorbic acid) Dispersed. At the bottom of a 24-well plate, a shield for inducing tissue regeneration of the present invention was mounted. The liquid in which the cell was dispersed was added to the shielding film by 30 ul. The density of the cells added was 1 x 10 ⁵ cells per matrix of 1 x 1 cm ² . Cell inoculation was incubated for 3 hours in an incubator at 37 ℃, 5% CO ₂ condition to allow the cells to adhere. Thereafter, 1 ml of the culture solution was added, and the culture solution was exchanged every 2 to 3 days.

On 1 and 7 days after the culture, the shielding membrane to which cells were attached was collected. The operation for observing the state and differentiation degree of the cells attached to each shielding membrane under differential scanning microscope (SEM) is as follows. The osteoblast-attached membranes were washed to remove unattached cells and pre-fixed for 40 minutes at 4 ° C. in 2.5% glutaraldehyde solution dissolved in 0.1 M phosphate buffered saline (PBS, pH 7.4). After fixation, the resultant was washed with 0.1 M phosphate buffered saline solution, and then fixed in osmium tetroxide dissolved in 0.1 M phosphate buffered saline solution at 1% concentration for 40 minutes at 0 ° C. After fixation, the cells were stored at −70 ° C. for 24 hours and lyophilized. Lyophilized samples were observed by differential scanning microscope (SEM) by gold-palladium coating.

As a result of the osteoblast adhesion test of the membrane of the present invention, Figure 3a is a result of observing with a differential scanning micrograph after attaching the osteoblasts of the membrane prepared in Example 1 for 1 day, 1 of the membrane for inducing tissue regeneration of the present invention As a result of osteoblast adhesion, the cells showed spherical and elongated morphology that began to adhere to the shielding membrane. Most of the cytoplasm is expanded to show a flat shape, so that adhesion is stable within 1 day, and thus a flat form is observed, so that the stable adhesion of osteoblasts can be seen. FIG. 3B shows the osteoblasts of the membrane prepared in Example 1 for 7 days. As a result, the expansion of the cytoplasm into the radiographic image and the flattening of the cell center were observed, and it can be observed that these expanded cells form a layered layer forming a dendritic cell aggregate.

Therefore, as a result of FIG . 3A and FIG. 3B , stable adhesion and differentiation of osteoblasts were seen, which indicates that the tissue regeneration induction barrier of the present invention showed high cell affinity and biocompatibility.

As described above, the tissue regeneration induction shielding membrane of the present invention has an excellent shielding effect that sufficiently blocks the invasion of epithelial cells and connective tissues, helps the growth of bone tissue, and is designed as easily as desired during surgery to provide excellent surgical convenience. It has excellent product productivity and excellent mechanical strength, which has very good functionality.

Claims (15)

A membrane for inducing tissue regeneration in which a porous biodegradable polymer membrane sandwiched with micropores between chitosan nonwoven fabrics is sandwiched. The shielding membrane according to claim 1, wherein the polymer used for producing the biodegradable polymer membrane is a biodegradable polyester polymer. 3. The shielding film according to claim 2, wherein the biodegradable polyester polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polylactic acid-glycolic acid copolymer, and polycaprolactone. The shielding film according to claim 1, wherein the biodegradable polymer film has a thickness of 0.01 to 10 mm. The method of claim 1, wherein the chitosan nonwoven fabric further comprises selected from the group consisting of an extracellular matrix component to improve biocompatibility, a ceramic component to improve the mechanical strength and bone tissue regeneration effect, and mixtures thereof. Shielding film. 6. The shielding film according to claim 5, wherein the ceramic component is tricalcium phosphate or calcium metaphosphate. The shielding film according to claim 1, wherein the chitosan nonwoven fabric has a fiber thickness of 0.001 to 400 µm. a) spinning a biodegradable polymeric material in a spinning device to obtain a chitosan nonwoven fabric, b) applying a mixed solution of a main solvent and a subsolvent of a biodegradable polymer material on the surface of the obtained nonwoven fabric to form a biodegradable polymer film having micropores, c) laminating and pressing the chitosan nonwoven fabric obtained above on the surface of the obtained biodegradable polymer membrane and then drying. The method of claim 8, wherein the chitosan nonwoven fabric is produced by solution spinning, melt spinning or melt brown. The method of claim 9, wherein the chitosan nonwoven fabric is produced by solution spinning. 9. The method according to claim 8, wherein the main solvent is methylene chloride. 9. A process according to claim 8, wherein said subsolvent is selected from the group consisting of ethyl acetate, dioxane and chloroform. 9. The process according to claim 8, wherein the main solvent is methylene chloride and the subsolvent is ethyl acetate. The coagulating solution of the spinning process is selected from the group consisting of a mixed solvent of potassium hydroxide and ethylene glycol, a mixed solvent of sodium hydroxide and ethylene glycol, potassium hydroxide solution, sodium hydroxide solution, ethanol, methanol and acetone Manufacturing method characterized in that. The method of claim 8, wherein the solvent during spinning is acetic acid, lactic acid, hydrochloric acid, and the like.