JP2008163520A - Chitosan/sericin composite nanofiber and utilization of the same to artificial skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a medical material safe as a material for artificial organs such as artificial skin or as a wound-covering material, and high in tissue regenerative ability as well, and to provide artificial organs, wound-covering materials, etc. each using the medical material. <P>SOLUTION: A fiber 50-500 nm in average diameter comprising a chitosan/sericin composite is prepared by electric field spinning process. A fiber mat made of the fiber is useful as an artificial skin, a wound-covering material or the like, and as a medical material such as a scaffold for regenerating various organs including the skin, capillary, cartilage and bone. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a functional nanofiber formed by a complex of chitosan and sericin, a production method thereof, and a medical material obtained from the fiber.

  Traditional skin transplants or self-cultured skin damage caused by severe burns and scars, pressure ulcers due to bed slippage, diabetic ulcers, severe atopic dermatitis, skin damage caused by traffic accidents, etc. Although skin transplantation has been performed, in the case of severe damage reaching the dermis, the engraftment rate of the transplanted skin is not always good and re-transplantation may be necessary, so the burden on the patient is small In addition, self-cultivation was not always satisfactory because it could not cope in an emergency.

In recent years, as part of regenerative medicine, research and development of artificial skin using biocompatible materials such as natural and synthetic polymer materials has been promoted. For example, artificial skin using collagen as a base material for cultured skin Production examples (Patent Document 1), medical materials made of a DNA / chitosan complex (Patent Document 2), artificial skin made of chitin fibers (Non-Patent Document 1), and the like have been reported.
In addition, since tissue regeneration requires a three-dimensional structure as a scaffold, the artificial skin material has sufficient mechanical strength and cell adhesion in addition to biocompatibility and safety. There is a demand for a specific surface area or a porous structure that can supply oxygen and nutrients to form an invasion path for cells and regenerated tissue.
As the three-dimensional structure that functions as a scaffold, sponge bodies, honeycomb bodies, or nonwoven fabrics in which fibers are layered are known, but as the fibers constituting the nonwoven fabric, conventionally known micrometer order ( In addition to ultrafine fibers (micron order), the development and commercialization of thinner nanometer order fibers (nanofibers) are underway. Nanofibers usually have an average diameter of 100 nm or less, and have a much larger specific surface area than conventional ultrafine fibers, which is advantageous in terms of cell adhesion efficiency. Moreover, since the nonwoven fabric prepared from the said fiber approximates the microscopic structure of the extracellular matrix in vivo, the application to regenerative medicine is considered.

For example, Patent Document 3 discloses a medical material including a nonwoven fabric of fibers having an outer diameter of several nanometers to several tens of micrometers using a natural polymer material such as gelatin or collagen or a synthetic polymer material such as polyurethane. In addition, Patent Document 4 describes a fiber having a diameter of 500 nm or less using a polysaccharide such as chitosan, chondroitin sulfate, and pectin as a main raw material.
JP-A-9-173362 JP 2005-289852 A JP 2004-321484 A JP-A-2005-290610 Chitin Chitosan Study Group, “Chichin Chitosan Handbook”, 336-343, Gihodo Publishing, 1995

As described above, the use of some natural polymer materials or synthetic polymer materials as artificial skin materials has been attempted. For example, in the case of artificial skin made of chitin fibers, the fiber diameter is on the order of micrometers. For this reason, there are problems such as insufficient engraftment and the use of a highly toxic special reagent for its production, and the necessity of several steps for the production of non-woven fabric after spinning of chitin yarn. It was not always satisfactory.
Therefore, the problem to be solved by the present invention is to provide a medical material that is safe as a material for an artificial organ such as artificial skin or as a wound dressing and has a high tissue regeneration ability, and an artificial material using the same. It is to provide organs and wound dressings.

  As a result of earnest research on medical materials for artificial skin and the like, the present inventor succeeded in fiberizing a complex of chitosan and sericin into nanofibers using a highly safe reagent. The present invention has been completed by finding that nanofibers have an excellent effect that has not been achieved as a functional fiber for medical use for artificial skin and wound dressing.

That is, the present invention
(1) A fiber having an average diameter of 50 to 500 nm, comprising a complex of chitosan and sericin.
(2) The fiber according to (1), wherein the weight ratio of chitosan and sericin is 60 to 90:40 to 10.
(3) The fiber according to (2), wherein the weight ratio of chitosan and sericin is 80:20.
(4) The fiber according to any one of (1) to (3), further comprising a synthetic polymer material.
(5) The fiber according to (4), wherein the synthetic polymer material is any one or more of polyethylene oxide, polyvinyl alcohol, and PVP.
(6) The method for producing a fiber according to any one of (1) to (5), comprising dissolving chitosan and sericin in water in the presence of an acid and electrospinning the aqueous solution.
(7) The production method according to (6), wherein the acid is acetic acid.
(8) The production method according to (6) or (7), comprising dissolving polyethylene oxide in the aqueous solution.
(9) A mat comprising the fiber according to any one of (1) to (5).
(10) A medical material comprising the mat according to (9).
(11) The medical material according to (10), which is artificial skin.
(12) The medical material according to (10), which is a wound dressing.

  The nanofibers of the chitosan / sericin composite according to the present invention have a very large specific surface area compared to conventional micron-order fibers, so that the non-woven thin film or mat obtained from the fibers has a high porosity. Have Therefore, it is excellent in absorbability of bodily fluids and has hemostatic action and bacteria growth inhibitory action, so when used as artificial skin or wound dressing material, when the thin film or mat is brought into contact with the damaged site, it adheres well to the damaged surface. The adhesion area is large, and the interstitial structure (pore structure) between the fibers approximates in vivo, which is advantageous for cell / tissue regeneration. Furthermore, since the thin film or mat has extremely high flexibility, it is excellent in a feeling of mounting on a damaged surface. The wound healing promoting effect of the chitosan / sericin complex according to the present invention is remarkably superior to that of chitosan alone.

[Raw material solution]
Chitosan is a polysaccharide obtained by deacetylating chitin obtained mainly from crustaceans such as crabs and shrimps, insects, shellfish, mushrooms, etc., and usually refers to those having a degree of deacetylation of 60% or more. However, in the present invention, those having about 70% or more, more preferably about 80% or more, and further preferably about 90% or more are used. There are three types of chitin, α-type, β-type, and γ-type, depending on the molecular crystal structure. Chitosan using any chitin may be used.
The molecular weight of chitosan varies from, for example, 30,000 to 1,000,000 depending on the production method, and is not particularly limited in the present invention. However, if the molecular weight becomes too large, the solubility decreases, and there is a problem in solution concentration, viscosity, and spinnability. Therefore, a relatively low molecular weight of about 50,000 to 250,000 is preferable.
Sericin is a protein that is contained in an amount of 20 to 30% in the form of surrounding fibroin in the cocoon, and is obtained by recovering from waste liquid in the refining process for obtaining silk thread (fibroin thread). The molecular weight of sericin ranges from about 20,000 to over 500,000, and is not particularly limited in the present invention, but is preferably about 2 to 50,000.
Both chitosan and sericin are available as commercial products.
In the present invention, the chitosan / sericin complex refers to a simple mixture of chitosan and sericin, an electrostatic bond, a van der Waals conjugate, or the like, and may partially include a covalent bond.
In the chitosan / sericin complex of the present invention, the mixing ratio of chitosan and sericin is about 60 to 90:40 to 10 and preferably about 70 to 85:30 to 15 by weight. If the amount of chitosan is less than 60%, the spinnability tends to deteriorate, and if it exceeds 90%, the blending effect of sericin becomes dilute, which is not preferable.

  In addition to chitosan and sericin, the raw material of the fiber of the present invention contains natural and synthetic polymer substances up to 40% by weight, preferably 10-30% by weight, based on the total weight 100 of the chitosan / sericin complex. be able to. Natural polymer materials include collagen, gelatin, chitin, fibroin, chondroitin sulfate, hyaluronic acid, pectin and the like, and synthetic polymer materials include polyethylene oxide, polyethylene glycol, polyvinyl alcohol, PVP, polylactic acid, polyglycol. Of these, synthetic polymer substances such as polyethylene oxide (PEO), polyvinyl alcohol (PVA), and polyvinyl pyrrolidone (PVP) are preferably blended to improve the spinnability. These synthetic polymer substances have a molecular weight of about 100,000 to 1,000,000, and preferably about 300 to 500,000. The blending amount of the synthetic polymer material for improving the spinnability is as described above, but when the molecular weight of chitosan is as small as about 100,000, a smaller amount may be used, and spinning with a blending of about 2.5%. Can improve sex.

  The chitosan / sericin composite fiber in the present invention is a fiber having an average diameter of 50 to 500 nm, preferably 100 to 200 nm, and is produced by electrospinning a mixed solution of chitosan and sericin using an electrospinning apparatus. .

[Electrospinning]
An electrospinning apparatus for obtaining nanofibers is, for example, as shown in FIG. 1, and includes a needle syringe (1), a nozzle (needle) (2), a substrate (3), a DC high voltage power source (4), A fusion pump (5) is provided.
When a high voltage is applied between the nozzle tip and the substrate 3 when the polymer solution remains at the tip of the nozzle 2 of the syringe 1 due to the action of surface tension, the electrostatic repulsive force of the polymer solution exceeds the surface tension at the nozzle tip, The solution is continuously discharged from the tip of the nozzle, and is collected on the substrate as a long fiber sheet in a fiber shape.
Further, as shown in FIG. 2, if the substrate is changed to a cylindrical rotating body, a tubular medical material such as an artificial blood vessel can be obtained.
The polymer concentration of the raw material solution, the discharge speed, the applied voltage, the type of polymer, the type of solvent, etc. are appropriately set. Generally, the polymer concentration is 3 to 20% by weight, preferably 7 to 15% by weight, and the discharge speed is 0. 1 to 10 ml / hr, preferably 1 to 3 ml / hr, applied voltage of 5 to 35 kV, preferably 15 to 27 kV.
The distance between the syringe and the substrate is 4 to 30 cm, preferably 8 to 15 cm, the temperature in the apparatus is room temperature ± 10 ° C., and the humidity is 30 to 70% relative humidity, preferably 40 to 60%.
If the applied voltage is made larger than the above range or the syringe / substrate distance is made narrower than the above range, there is a risk of discharge between the nozzle and the substrate. If the distance is larger than the above range or the relative humidity is out of the above range, the spinnability tends to be poor.

The syringe is filled with the raw material solution, and the positive side of the high-voltage power supply is connected to the nozzle tip and the negative side is connected to the substrate, and a high voltage is applied and integrated on the substrate.
The substrate may be of any shape and size as long as it has a metal having good conductivity such as copper or aluminum and can serve as an electrode when a high voltage is applied. For example, in FIGS. An insulating sheet such as a sheet (polyethylene terephthalate (PET)) is laminated, the insulating sheet is cut to an appropriate size, and the cut peripheral edge is edged with a copper tape to form a nanofiber receiving portion. A fiber sheet such as paper or gauze may be laid on the fiber receiving portion.

The preparation method of the raw material solution used for electrospinning is not particularly limited. For example, chitosan is dissolved in water in advance, and sericin is added to obtain a raw material solution.
Since chitosan is hardly soluble in water, it is preferable to add an organic acid or an inorganic acid to aid dissolution. Examples of organic acids include formic acid, acetic acid, propionic acid, butyric acid, citric acid, tartaric acid, lactic acid, ascorbic acid, and glycolic acid. Examples of inorganic acids include hydrochloric acid and nitric acid. The amount of the acid used depends on the molecular weight of chitosan, but is 20 to 80% by weight, preferably 40 to 70% by weight, based on 100 parts by weight of chitosan. If the amount is too high, the amount of residual acid increases, making it unsuitable for artificial skin.
In the case of adding another polymer substance, a polymer substance solution is separately prepared, added to the chitosan / sericin solution, and sufficiently stirred to obtain a raw material solution.
In preparation of the aqueous solution of each raw material, it may be heated to about 30 to 60 ° C. if necessary.

The operation of electrospinning is to fill the syringe 1 of the electrospinning apparatus with the raw material solution, adjust the atmospheric humidity in the apparatus to 30 to 70%, and then apply the high voltage to collect the nanofibers on the substrate. A thin film is formed. Although the thickness of a thin film is arbitrary according to a use, when using it as artificial skin, it shall be about 50 micrometers-100 micrometers, for example. The nanofiber thin film and mat deposited on the substrate may be neutralized. In that case, the target thin film and mat are obtained by neutralization and then washing and drying.
The neutralization method may be any method such as immersing in an alkaline aqueous solution such as sodium hydroxide, potassium hydroxide, sodium bicarbonate, spraying the alkaline aqueous solution, or leaving in an ammonia saturated vapor.

[Usage]
The nanofiber of the present invention has a very large specific surface area, and the non-woven thin film or mat on which the fiber is deposited has a pore structure that approximates the microscopic structure of the extracellular matrix in vivo, and is damaged. It functions as an excellent scaffold in the regeneration of deficient biological tissue. Therefore, the nanofiber of the present invention, or the thin film or mat thereof, is formed into a shape / structure corresponding to a damaged or deficient biological tissue site, and is used for skin, blood vessels, nerves, bones, cartilage, esophagus, valves, other organs. Can be used directly for regeneration, and can also be used as a scaffold in tissue culture in vitro.
The nanofiber of the present invention can be further used as a wound dressing by forming a surgical suture or a non-woven thin film and laminating it on an adhesive sheet as necessary. The wound dressing of the present invention can significantly promote natural healing simply by contacting the wound surface without using a drug.

  Hereinafter, examples and comparative examples will be described in more detail, but the present invention is not limited to these examples.

[Example 1] Electrospinning 1
Table 1 shows chitosan (molecular weight 217,000: manufactured by Katakura Chikkarin), sericin (molecular weight 30,000: manufactured by Seiren Co., Ltd.), PEO (molecular weight 400,000: manufactured by SCIENTIFIC POLYMER PRODUCTS), and distilled water. The amount used was used. Chitosan was immersed in distilled water for 30 minutes, acetic acid was added, and the mixture was stirred for about 4 hours to obtain an aqueous chitosan solution. Subsequently, sericin and PEO were added, and it stirred for about 8 hours, heating at about 40-50 degreeC, and obtained chitosan / sericin / PEO aqueous solution.
This aqueous solution is filled into the syringe 1 of the electrospinning apparatus in FIG. 1A, the distance between the nozzle and the substrate is adjusted to 8 cm, the atmosphere in the apparatus is adjusted to a relative humidity of about 50%, and then the applied voltage is 25 to 30 kV, the discharge speed is 2 ml / The fiber was continuously spun from the nozzle tip with hr, and the fibers were collected on the substrate of FIG. 1A. As shown in FIG. 1B, the substrate is formed by laminating a polyethylene terephthalate (PET) sheet 6 on a copper plate, making a 2 cm square hole in the PET sheet, attaching a copper tape 8 to the outer periphery of the hole, and attaching a high voltage negative electrode. The paper tape 7 was set on the bottom of the attachment and the hole to form a nanofiber receiving part.
After the surface of the sample film was vapor-deposited with metal (Au) by E-101 type ion sputtering, it was observed with a scanning electron microscope (SEM) (Hitachi model S-2300 type) at an acceleration voltage of 25 kV and a working distance of 25 mm. As shown in FIGS. 3A and 3B, a nanofiber nonwoven fabric having an average diameter of about 170 nm was shown.

[Example 2] Electrospinning 2
The nanofiber mat obtained in Example 1 was neutralized by immersing it in a 5% aqueous NaOH solution for about 1 hour, washed with water three times, and dried to obtain a nanofiber mat. 3C and 3D show SEM images.
[Example 3] Electrospinning 3
The nanofiber mat obtained in Example 1 was neutralized by leaving it in saturated steam of 5% NH ₃ aqueous solution for 4 days, then washed with water and dried to obtain a nanofiber mat.
[Example 4] Electrospinning 4
A nanofiber mat was obtained in the same manner as in Example 1 except that the amounts of chitosan, sericin, PEO, and distilled water were changed as shown in Table 1.
[Example 5] Electrospinning 5
The nanofiber mat obtained in Example 4 was neutralized by immersing it in a 5% NaOH aqueous solution for about 1 hour, washed with water three times, and dried to obtain a nanofiber mat.

[Example 6] Electrospinning 6
A nanofiber mat was obtained in the same manner as in Example 1 except that the amounts of chitosan, sericin, PEO, and distilled water were changed as shown in Table 1.
The obtained nanofiber mat was folded to 10 × 3 mm, adjusted to a thickness of 0.1 mm, sufficiently dried in a desiccator, and subjected to wide angle X-ray diffraction (WAXD) measurement.
The measurement is performed by photographing for 8 hours with a Toshiba XC-40H wide-angle X-ray diffractometer (collimator 0.5 mm diameter, camera length 32 mm) and CuKα rays (Ni filter filtration) (40 kV, 20 mA). (FIG. 4).
Using the same sample, the wide-angle X-ray diffraction intensity was measured on the equator line (β = 0 °).
RINT2100 manufactured by Rigaku Corporation was used for the measurement, scanning range 2θ: 3 ° to 40 °, scanning speed: 1 ° / min, scanning axis: 2θ / θ, X-ray: CuKα ray (tube voltage 40 kV, tube current 20 mA) It carried out using Ni filter filtration X ray (FIGS. 5-7).
FIG. 5 shows WAXD intensity curves of sericin powder, FIG. 6 of PEO powder, and FIG. 7 of chitosan / sericin / PEO = 7/3/2 nanofibers.
According to FIG. 7, diffraction peaks appeared in a form similar to chitosan neutralized to 2θ = 9.52 °, 20.8 °, 23.1 °, 29.8 °, 35.2 °. Since the X-ray diffraction intensity curve before neutralization resembles the X-ray diffraction intensity curve after neutralization, it is considered that the acetic acid solution diffused during electrospinning and almost no acetic acid remained in the nanofibers. The diffraction peaks appearing at 2θ = 16.0 °, 20.8 °, 23.1 °, and 36.4 ° are considered to be the influence of slightly mixed PEO. Since the two meridian reflections at 2θ = 29.8 ° and 35.2 ° are strong, the nanofibers appear to exhibit a high molecular orientation.
FIG. 5 shows that sericin has low crystallinity, and FIG. 6 shows that PEO shows clear crystal diffraction.

[Example 7] Electrospinning 7
The nanofiber mat obtained in Example 6 was neutralized by immersing it in a 5% NaOH aqueous solution for about 1 hour, washed with water three times, and dried to obtain a nanofiber mat.
[Comparative Example 1]
Except for using a raw material solution prepared using 6 g of chitosan (molecular weight 100,000: manufactured by Fuji Boseki Co., Ltd.), PEO (molecular weight 400,000: manufactured by SCIENTIFIC POLYMER PRODUCTS) 4 g, acetic acid 3 g and distilled water 87 g. A nanofiber mat was obtained in the same manner as in Example 3.
[Comparative Example 2]
A nanofiber mat was obtained in the same manner as in Example 1 except that the materials used in Comparative Example 1 were used in the proportions shown in Table 1.

[Example 8] Wound treatment effect 1 (Healing effect on shallow wound of epidermis only)
Wound preparation: A hair removal agent was applied to the back of the mouse and left for about 3 minutes. Thereafter, the epidermis was scraped off and a wound was prepared.
Nanofiber mat adhesive tape: The nanofiber mat obtained in Example 1 was cut into 1 × 2 cm and adhered to the center of the adhesive tape to prepare an adhesive tape.
Wound treatment: The nanofiber mat surface of the adhesive tape was affixed to the wound site of the mouse, peeled off every 0, 3, 6, and 10 days, and the therapeutic effect was observed using the mouse without the mat as a control. The visual treatment results are shown in Table 2, and photographs of wounds after 0, 3, 6, and 10 days are shown in FIGS. 8A, 9A, 10A, and 11A. After observation, a new adhesive tape was applied.
On the 10th day after application, the skin in the treatment area was cut out, fixed and sliced, and stained with hematoxylin and eosin, and the skin cross section was observed (FIG. 12A).
Except for using the nanofiber mats obtained in Examples 2, 3, 5 and 7, the wound treatment effects were observed in the same manner as described above (Table 2, FIGS. 8B to E, 9B to E, 10B). -E, 11B-E, 12B-E).

In the table, C is chitosan, S is sericin, P is PEO, the numerical value is the blending weight of the three components, Un is a fiber mat that is not neutralized, Na is a fiber mat that is neutralized with sodium hydroxide means.
As is clear from the results in Table 2, all the cases with the mat of the present invention applied to the shallow wound only on the epidermis showed good results on the 10th day of the wound treatment as compared with the control. Also in the follow-up observation, the mats of the present invention showed improvement in comparison with the control in almost all cases.
There is a slight difference in the course of treatment with the three types of CSP822, and the Un type was advantageous because of the excellent biocompatibility of sericin. On the other hand, in the neutralized Na type and NH ₃ type, it is estimated that some sericin was eluted during the neutralization / water washing process.
Further, using the fiber mat obtained in Comparative Example 1, in the same manner as in Example 8, the healing effect on shallow wounds on the epidermis was observed. FIG. 13 shows a photographic image of the wound part on the 10th day, and FIG. 14 shows a cross-sectional image of the skin.

[Example 9] Wound treatment effect 2 (healing effect for deep wounds up to the dermis)
Wound creation: The epidermis on the back of the mouse was rubbed hard with a metal brush to make a wound reaching the dermis layer.
Thereafter, as in Example 8, the mat surface of the adhesive tape on which the nanofiber mat obtained in Example 1 was attached was affixed to the wound site of the mouse, and peeled off on the 0th, 3rd, and 6th days. The therapeutic effect was observed using a mouse to which no affixed as a control. The visual treatment results are shown in Table 3, and photographs of wounds after 0, 3, and 6 days are shown in FIGS. After observation, a new adhesive tape was applied.
On the 6th day after application, the skin of the treatment area was cut out, fixed and sliced, and stained with hematoxylin and eosin, and the cross section of the skin was observed (FIG. 17A).
Except for using the nanofiber mats obtained in Example 4 and Comparative Example 2, the effect of treating deep wounds was observed in the same manner as described above (FIGS. 15, 16D to F, FIGS. 17B and b). .
From the images in Table 3 and FIGS. 15 to 17, it was revealed that healing and regeneration of damaged skin due to deep wounds were promoted when treated with the mat of the present invention.

  When the experimental results of Examples 8 and 9 are combined, CSP822 · Un can be said to be an optimal artificial skin / wound dressing material in that it can be applied not only to a shallow wound only on the epidermis but also to a deep wound reaching the dermis.

A: Schematic diagram of the electrospinning apparatus 1; B: Schematic diagram of a substrate that becomes a fiber receiving part in the electrospinning apparatus. It is a schematic diagram of the electrospinning apparatus 2. A: Scanning electron microscope image (× 30k) of the fiber mat obtained in Example 1, B: Scanning electron microscope image (× 3k) of the fiber mat obtained in Example 1, C: Example 2 is a scanning electron microscope image (× 30k) of the fiber mat obtained in 2, and D: a scanning electron microscope image (× 3k) of the fiber mat obtained in Example 2. The wide-angle X-ray photograph image of the nanofiber obtained in Example 6. Wide angle X-ray intensity curve of sericin powder. Wide angle X-ray intensity curve of PEO powder. Wide angle X-ray intensity curve of nanofiber of chitosan / sericin / PEO = 7/3/2. The wound part photographic image immediately after the wound treatment in Example 8. a: Control, A: Nanofiber mat of Example 1, B: Nanofiber mat of Example 2, C: Nanofiber mat of Example 3, D: Nanofiber mat of Example 5, E: The nanofiber mat of Example 7. The wound part photograph image of the coating | coated 3rd day in Example 8. FIG. a: Control, A: Nanofiber mat of Example 1, B: Nanofiber mat of Example 2, C: Nanofiber mat of Example 3, D: Nanofiber mat of Example 5, E: The nanofiber mat of Example 7. The wound part photograph image of the coating | coated 6th day in Example 8. FIG. a: Control, A: Nanofiber mat of Example 1, B: Nanofiber mat of Example 2, C: Nanofiber mat of Example 3, D: Nanofiber mat of Example 5, E: The nanofiber mat of Example 7. The wound part photograph image of the coating | coated 10th day in Example 8. FIG. a: Control, A: Nanofiber mat of Example 1, B: Nanofiber mat of Example 2, C: Nanofiber mat of Example 3, D: Nanofiber mat of Example 5, E: The nanofiber mat of Example 7. The wound part skin cross-section photograph image of the coating | coated 10th day in Example 8. FIG. a: Control, A: Nanofiber mat of Example 1, B: Nanofiber mat of Example 2, C: Nanofiber mat of Example 3, D: Nanofiber mat of Example 5, E: The nanofiber mat of Example 7. The wound part photograph image at the time of using the nanofiber mat of the comparative example 1. a: Control, b: Day 10 after wound treatment of control, A: Immediately after wound treatment, B: Day 10 of coating with nanofiber mat of Comparative Example 1. The wound part skin cross-section photograph image of the 10th day at the time of using the nanofiber mat of the comparative example 1. FIG. a: cross section of untreated skin (× 4), b: cross section of skin with peeled epidermis (× 10), c: control (× 10), A: nanofiber mat of Comparative Example 1 (× 4) Photo 9 of wound part in Example 9 a: Immediately after wound treatment (control), b: Day 3 of wound treatment, c: Day 6 of wound treatment, d: Immediately after wound treatment (Nanofaber mat of Comparative Example 2) ), E: the third day of coating with the nanofiber mat of Comparative Example 2, and f: the sixth day of coating with the nanofiber mat of Comparative Example 2. Photo image 2 of wound part in Example 9 A: Immediately after wound treatment (Nanofiber mat of Example 1), B: Third day of coating with nanofiber mat of Example 1, C: Nano of Example 1 6 days after coating with fiber mat, D: immediately after wound treatment (nanofiber mat of Example 4), E: 3 days of coating with nanofiber mat of Example 4, F: nanofibers of Example 4 Covering with mat 6th day. The skin cross-sectional photographic image on the 6th day of wound treatment in Example 9. FIG. a: Control, b: Nanofiber mat of Comparative Example 2, A: Nanofiber mat of Example 1, B: Nanofiber mat of Example 4.

Explanation of symbols

1 Syringe 2 Nozzle (needle)
3 Substrate 4 DC high voltage power supply 5 Infusion pump
6 PET sheet 7 Paper tape 8 Copper tape

Claims (12)

  A fiber having an average diameter of 50 to 500 nm, comprising a complex of chitosan and sericin.   The fiber according to claim 1, wherein the weight ratio of chitosan to sericin is 60 to 90:40 to 10.   The fiber according to claim 2, wherein the weight ratio of chitosan to sericin is 80:20.   Furthermore, the fiber of any one of Claims 1-3 containing a synthetic polymer material.   The fiber according to claim 4, wherein the synthetic polymer material is one or more of polyethylene oxide, polyvinyl alcohol, and PVP.   The manufacturing method of the fiber of any one of Claims 1-5 which melt | dissolves chitosan and serine in water in presence of an acid, and electrospins the said aqueous solution.   The production method according to claim 6, wherein the acid is acetic acid.   The production method according to claim 6 or 7, comprising dissolving polyethylene oxide in the aqueous solution.   The mat which consists of a fiber of any one of Claims 1-5.   A medical material comprising the mat according to claim 9.   The medical material according to claim 10, which is artificial skin. The medical material according to claim 10, which is a wound dressing.