TWI537014B - Fibrous sponge dressing and manufacturing method thereof - Google Patents

Description

Fiber sponge material and manufacturing method thereof

The present invention relates to a sponge material and a method of manufacturing the same, and more particularly to a fiber sponge material and a method of manufacturing the same.

In the traditional wound treatment mode, it is generally believed that the dryness of the wound can provide a better environment for wound healing and make the wound easier to heal. Therefore, medical gauze is often used to avoid wound infection and keep the wound dry and clean. However, in recent years, research has pointed out that in a humid environment, the effect of healing wounds is better, and based on the research results, several wet advanced dressings such as hydrogels and hydrophilic colloidal dressings have been developed. Hydrocolloid), Semi-permeable film, Alginate, Hydrofiber, Foam and Collagens, among which Collagen Protein dressings are biodegradable, absorbable, moisturizing and can be used in combination with other drugs. They are the standard products in wet advanced dressings.

However, the collagen dressings currently on the market are expensive, difficult to popularize, and have doubts about the immunity of animal pathogens. In addition, collagen The decomposition rate of the dressing material is too fast, so it is necessary to fill it repeatedly when treating the wound, which is inconvenient to use.

In view of this, there is a need for a fibrous sponge material in which the fibrous sponge material is biodegradable, has a decomposition time course that can match the time of tissue repair, does not need to be replaced during the treatment of the wound, is convenient to use, and costs more than collagen. The advantages of low protein and so on.

The present invention provides a fibrous sponge material comprising a sponge-like fibrous structure, a polysaccharide, and a chitin degrading enzyme. The spongy fiber structure comprises chitin fiber and poly(lactic acid-glycolic acid) copolymer fiber, and the chitin fiber accounts for 3 parts by weight, and the poly(lactic acid-glycolic acid) copolymer fiber accounts for 1 to 9 parts by weight. The polysaccharide body is dispersed in the sponge-like fibrous structure and accounts for 1.33 to 20 parts by weight. The chitin degrading enzyme is dispersed in a sponge-like fibrous structure and has a content of 1 to 100 U. Among them, 1U represents the amount of enzyme required for chitin to decompose chitin at a pH of 6.0 and a temperature of 25 ° C to release 1.0 mg of N -acetyl glucosamine in one hour.

In one embodiment of the invention, the crystallinity of chitin is less than 5%.

In one embodiment of the invention, the molecular weight of chitin is 5 to 100 kDa.

In one embodiment of the invention, the degree of deacetylation of chitin is greater than 95%.

In one embodiment of the present invention, the poly(lactic-glycolic acid) copolymer has a copolymerization ratio of lactic acid to glycolic acid of 50:50 to 75:25.

In one embodiment of the invention, the poly(lactic-glycolic acid) copolymer has a molecular weight of from 5 to 100 kDa.

In one embodiment of the present invention, the chitin fiber and the poly(lactic acid-glycolic acid) copolymer fiber have a diameter of 1 to 20 μm.

In one embodiment of the invention, the polysaccharide body comprises hyaluronic acid and alginic acid.

In one embodiment of the present invention, hyaluronic acid accounts for 0.8 to 12 parts by weight, and alginic acid accounts for 0.53 to 8 parts by weight.

In an embodiment of the invention, the fiber sponge material further comprises a crosslinking agent, which is 0.68~3 parts by weight.

In one embodiment of the invention, the chitin degrading enzyme is present in an amount from 1 to 20 U.

In one embodiment of the invention, the fibrous sponge material has a basis weight of from 100 to 300 g/m ² .

In one embodiment of the invention, the fibrous sponge material has a thickness of from 0.5 to 20 mm.

In one embodiment of the invention, the fibrous sponge material is a fibrous sponge material that simulates a cortical structure.

The present invention further provides a method for producing a fibrous sponge material comprising 3 parts by weight of chitin fiber, 1 to 9 parts by weight of poly(lactic acid-glycolic acid) copolymer fiber, 1.33 to 20 parts by weight of polysaccharide, and chitin decomposition. The enzyme 1~100U is mixed in water to form a composite fiber solution, wherein 1U represents the decomposition of chitin by chitin decomposing enzyme at a pH of 6.0 and a temperature of 25 ° C, and 1.0 mg of N -acetyl glucosamine is released in one hour. The amount of enzyme needed. Next, the composite fiber liquid is freeze-dried to form a fiber sponge material. Wherein, the chitin fiber and the poly(lactic acid-glycolic acid) copolymer fiber form a sponge-like fiber structure of the fiber sponge material, and the polysaccharide body and the chitin decomposing enzyme are dispersed in the sponge fiber structure.

In one embodiment of the invention, the polysaccharide body comprises hyaluronic acid and alginic acid.

In one embodiment of the present invention, hyaluronic acid accounts for 0.8 to 12 parts by weight, and alginic acid accounts for 0.53 to 8 parts by weight.

In one embodiment of the present invention, the chitin degrading enzyme is added in an amount of 1 to 20 U.

In one embodiment of the present invention, the method of producing a fibrous sponge material further comprises adding 0.68 to 3 parts by weight of a crosslinking agent to be mixed in water to form a composite fiber liquid.

In one embodiment of the invention, the fibrous sponge material is a fibrous sponge material that simulates a cortical structure.

The fibrous sponge material of the present invention has a sponge-like fibrous structure, and it is subjected to gradient degradation during the treatment of the wound, thereby providing a suitable growth environment for the wound tissue. The fibrous sponge material of the present invention is a biodegradable material which is completely decomposed after about 1 to 3 months of treatment.

110, 120‧‧‧ steps

210, 220, 230, 240, 250, 260, 270, 310, 320, 330, 340, 350‧‧‧ lines

In order to make the features, advantages and embodiments of the present invention more apparent, the description of the drawings is as follows: Figure 1 shows a microscopic image of a conventional collagen sponge dressing.

Fig. 2 is a microscope image showing a fiber sponge material according to an embodiment of the present invention.

Fig. 3 is a schematic flow chart showing the manufacture of a fibrous sponge material according to an embodiment of the present invention.

Fig. 4 is a graph showing the degradation rate-time relationship between the examples of the present invention and the comparative examples.

Fig. 5 is a graph showing the wound healing rate-time relationship between the examples of the present invention and the comparative examples.

In order to make the description of the present invention more detailed and complete, the embodiments of the present invention are described with reference to the accompanying drawings. The embodiments disclosed herein may be combined or substituted with each other in an advantageous manner, and other embodiments may be added to an embodiment without further description or description. In the following description, numerous specific details are set forth However, embodiments of the invention may be practiced without these specific details.

At present, the biodegradable sponge dressing standard product on the market is a collagen sponge dressing. Please refer to Fig. 1, which is a microscope image showing a conventional collagen sponge material. As can be seen from the figure, the collagen sponge material is a sponge structure having a plurality of round holes, however, the structure of the collagen sponge material is stable. Poorly characterized, and the collagenase (Reagenase) in the receptor is decomposed, so that the decomposition rate is too fast, and it completely decomposes in about 1 week. Therefore, in the treatment of wounds, it is necessary to repeatedly fill the collagen sponge material, which is inconvenient to use. Since the collagen unit price is high, and the collagen sponge material needs to be repeatedly filled, the overall cost of the treatment is high. In addition, since the collagen sponge material is decomposed rapidly, the sponge material is decomposed before the tissue is regenerated into the sponge structure, and cannot be used as a scaffold for tissue growth, and thus an appropriate tissue regeneration environment cannot be provided. Therefore, the use of collagen sponge dressing to treat wounds, the decomposition rate is greater than the healing speed of the wound, easy to make granulation tissue (Granulation) and newly formed collagen tissue structure is uneven, and scars are easy to produce after wound healing. In addition, the source of collagen is mostly of animal origin, which makes collagen have doubts about the tissue immunity of animal pathogens (eg, mad cow disease, foot-and-mouth disease, avian influenza).

Therefore, the present invention provides a fibrous sponge material whose biodegradation time course can be adjusted with tissue repair time by about 1 to 3 months, and does not need to be replaced during the treatment of the wound. The fiber sponge material of the invention can adjust the fiber sponge material to be staged by stepwise adjustment, and the fiber sponge material has a tissue-like sponge fiber structure, which can provide suitable cell growth and tissue regeneration. The growth environment.

The fibrous sponge material of the present invention comprises a sponge-like fibrous structure, a polysaccharide, and a chitin degrading enzyme. The spongy fiber structure comprises chitin fiber and poly(lactic acid-glycolic acid) copolymer fiber, and the chitin fiber accounts for 3 parts by weight, and the poly(lactic acid-glycolic acid) copolymer fiber accounts for 1 to 9 parts by weight. The polysaccharide body is dispersed in the sponge-like fibrous structure and accounts for 1.33 to 20 parts by weight. The chitin degrading enzyme is dispersed in a sponge-like fibrous structure and has a content of 1 to 100 U. Among them, 1U represents the amount of enzyme required for chitin to decompose chitin at a pH of 6.0 and a temperature of 25 ° C to release 1.0 mg of N -acetyl glucosamine in one hour.

Chitin, also known as chitin, is a long-chain polymer formed by polymerizing N -acetylglucosamine as a monomer. In one embodiment of the invention, the crystallinity of chitin is less than 5%, for example 1%, 2%, 3% or 4%. The smaller the crystallinity of chitin, the easier the fiber sponge material to be decomposed. In one embodiment of the present invention, the molecular weight of chitin is 5 to 100 kDa, and may be, for example, 5 kDa, 10 kDa, 20 kDa, 30 kDa, 40 kDa, 50 kDa, 60 kDa, 70 kDa, 80 kDa, 90 kDa or 100 kDa. The molecular weight of chitin is preferably controlled within this range. If the molecular weight of chitin is too large, the obtained fibrous sponge material is not easily decomposed. In one embodiment of the invention, the degree of deacetylation of chitin is greater than 95%, such as 96%, 97%, 98%, 99% or 100%. The greater the degree of deacetylation of chitin, the more the amount of amino groups of chitin, the positively charged, thus having an antibacterial effect. Positively charged chitin interferes with the negative charge on the surface of the bacteria, altering the permeability of the bacterial cell wall, causing the outflow of material from the bacteria to cause bacterial death.

It is worth noting that the crystallinity and molecular weight of chitin are selected in order to control the biodegradation time of the fibrous sponge material in the range of 1 to 3 months.

Poly(lactic-co-glycolic acid copolymer, PLGA) is a copolymer of lactic acid and glycolic acid. In one embodiment of the present invention, the poly(lactic acid-glycolic acid) copolymer has a copolymerization ratio of lactic acid to glycolic acid of 50:50 to 75:25, for example, 50:50, 55:45, 60: 40, 65:35, 70:30 or 75:25. When the poly(lactic acid-glycolic acid) copolymer has a high content of lactic acid segments, it is decomposed faster. When the poly(lactic acid-glycolic acid) copolymer has a copolymerization ratio of 50:50, the decomposition rate is faster than the copolymerization ratio of 75:25. In one embodiment of the present invention, the poly(lactic-glycolic acid) copolymer has a molecular weight of 5 to 100 kDa, and may be, for example, 5 kDa, 10 kDa, 20 kDa, 30 kDa, 40 kDa, 50 kDa, 60 kDa, 70 kDa, 80 kDa, 90 kDa or 100 kDa. . The molecular weight of the poly(lactic acid-glycolic acid) copolymer is preferably controlled within this range, and the larger the molecular weight of the poly(lactic acid-glycolic acid) copolymer, the less easily the fiber sponge material obtained is decomposed and decomposed. The longer it takes.

It is worth noting that the copolymerization ratio and molecular weight of the poly(lactic-glycolic acid) copolymer are selected in order to control the biodegradation time of the fiber sponge material in the range of 1 to 3 months.

In one embodiment of the present invention, the chitin fiber and the poly(lactic acid-glycolic acid) copolymer fiber have a diameter of 1 to 20 μm.

The polysaccharide system is interspersed in a sponge-like fibrous structure composed of chitin fibers and poly(lactic-glycolic acid) copolymer fibers. One of the purpose of adding a polysaccharide to the fiber sponge material of the present invention is to enhance the biocompatibility and healing function of the fiber sponge material.

Another object is to provide a gradient degradation of the fibrous sponge applicator during the treatment of the wound. After the fibrous sponge material is applied to the wound, first, the new cells in the wound are attached with a sponge-like fibrous structure as a scaffold. When the polysaccharide in the spongy fibrous structure is gradually decomposed by the enzyme in a few days, after decomposing The space left is used to provide new tissue growth. Then, the spongy fiber structure is gradually decomposed, and the regenerated tissue gradually grows to the sea. Within the fibrous structure, it replaces the space occupied by the sponge-like fibrous structure. This progressively induces tissue regeneration, which in turn promotes wound healing. The fibrous sponge material is completely decomposed after about 1 to 3 months of treatment, and there is no need to change the dressing during the treatment period. The fiber sponge material of the present invention has a longer biodegradation time course than the conventional collagen sponge material, so that it takes a longer time to grow the stent during cell/tissue regeneration, and can provide an appropriate tissue growth environment. Therefore, the wound treated by the sponge-like fibrous structure of the present invention has a smooth and uniform appearance after tissue healing, and can reduce the occurrence of scars.

In one embodiment, the polysaccharide comprises hyaluronic acid and alginic acid, and the hyaluronic acid accounts for 0.8 to 12 parts by weight, and the alginic acid accounts for 0.53 to 8 parts by weight. Alginic acid as referred to herein includes alginic acid and its derived alginate, alginate such as sodium alginate and calcium alginate.

In an embodiment of the invention, the fiber sponge material further comprises a crosslinking agent, which is 0.68~3 parts by weight. In one embodiment, when the polysaccharide body comprises sodium alginate, the crosslinking agent may be a crosslinking agent having a divalent ion such as calcium chloride (CaCl ₂ ). In the preparation of the fibrous sponge material, the divalent calcium ion of the crosslinking agent replaces the sodium ion of sodium alginate to form a fibrous sponge material having calcium alginate. The calcium alginate structure is stable, so that the fibrous sponge material is not easily decomposed before use. When a fibrous sponge material with calcium alginate is used to treat a wound, the sodium ions in the body will replace the calcium ions, causing the calcium alginate to return to the sodium alginate, which is decomposed in the body.

Since the body does not have an enzyme capable of decomposing chitin, the fibrous sponge material of the present invention contains chitin decomposing enzyme, so that chitin in the fibrous sponge material can be decomposed when used. Chitin is decomposed by carapace The content of the enzyme is controlled by the enzyme, and the content of the enzyme is represented by the enzyme unit (Unit, U). The higher the content of chitin degrading enzyme, the faster the decomposition of chitin. In one embodiment, the chitin degrading enzyme is present in an amount from 1 to 100 U, preferably from 1 to 20 U, for example 1 U, 5 U, 10 U, 15 U or 20 U.

The fibrous sponge material of the present invention may further comprise a functional ingredient, for example, comprising an antibacterial substance such as silver, or the like, to impart an antibacterial effect to the fibrous sponge material, or to contain a growth factor to aid wound healing.

In one embodiment of the invention, the fibrous sponge material has a basis weight of from 100 to 300 g/m ² . The thickness of the fiber sponge material can be 0.5 to 20 mm. The area of the fibrous sponge material can be 10 cm x 10 cm (± 0.2 mm).

The fiber sponge material of the present invention is a fiber sponge material which simulates a cortical structure. The structure of the simulated cortical tissue creates an environment suitable for tissue regeneration at the wound.

The main system of the fiber sponge material of the invention is composed of chitin fiber and poly(lactic acid-glycolic acid) copolymer fiber, and has a sponge-like structure, which can improve the structural stability of the fiber sponge material, and the polysaccharide system Scattered in a sponge-like fibrous structure. Referring to Fig. 2, there is shown a microscope image of a fiber sponge material according to an embodiment of the present invention. The fibrous structure of the shell structure and the poly(lactic acid-glycolic acid) copolymer fiber in Fig. 2 are dispersed in the sheet structure of the polysaccharide. As can be seen from the figure, the fiber sponge material of the present invention is formed by interlacing two fibers to form a sponge-like structure having a plurality of pores, and the pores are not round holes. Compared with the structure of the collagen sponge material of Fig. 1, the fiber sponge material of the present invention is a fibrous sponge structure, and the structure of the skin tissue similar. Thus, the fibrous sponge sheath of the present invention provides a preferred tissue regeneration environment.

Please refer to FIG. 3, which is a schematic flow chart showing the manufacture of a fiber sponge material according to an embodiment of the present invention. The method for producing a fibrous sponge material of the present invention firstly mixes a chitin fiber, a poly(lactic acid-glycolic acid) copolymer fiber, a polysaccharide, and a chitin degrading enzyme in water to form a composite fiber liquid (step 110). The chitin fiber is added in an amount of 3 parts by weight, the poly(lactic acid-glycolic acid) copolymer fiber is added in an amount of 1 to 9 parts by weight, the polysaccharide is added in an amount of 1.33 to 20 parts by weight, and the chitin degrading enzyme is used. The amount of addition is 1~100U. Among them, 1U represents the amount of enzyme required for chitin to decompose chitin at a pH of 6.0 and a temperature of 25 ° C to release 1.0 mg of N -acetyl glucosamine in one hour. Next, the composite fiber liquid is freeze-dried to form a fiber sponge material (step 120). Wherein, the chitin fiber and the poly(lactic acid-glycolic acid) copolymer fiber form a sponge-like fiber structure of the fiber sponge material, and the polysaccharide body and the chitin decomposing enzyme are dispersed in the sponge fiber structure.

The chitin fiber can be produced by alkalizing a chitin with a high concentration of alkali and swelling and dissolving it in ice water, neutralizing the precipitation of chitin, and lowering the crystallinity of the chitin, and the chitin which is reduced in crystallinity is more easily decomposed. More specifically, the crystallinity of chitin is controlled to be less than 5%, the molecular weight is controlled at 5 to 100 kDa, and the degree of deacetylation is controlled to be greater than 95%. Next, chitin is fiberized to form a chitin fiber.

The poly(lactic-glycolic acid) copolymer fiber can be produced by copolymerizing a lactic acid monomer with a glycolic acid monomer, and controlling the copolymerization ratio at 50:50 to 75:25, and controlling the molecular weight to 5 to 100 kDa. To form a poly (milk Acid-glycolic acid) copolymer. Next, the poly(lactic-glycolic acid) copolymer is fiberized to form a poly(lactic-glycolic acid) copolymer fiber.

In one embodiment, the polysaccharide body comprises hyaluronic acid and alginic acid, and the amount of hyaluronic acid added is 0.8 to 12 parts by weight, and the amount of alginic acid added is 0.53 to 8 parts by weight.

The fibrous sponge material is formed by lyophilization of the composite fiber liquid to remove water, and the chitin decomposing enzyme loses activity because the material does not have moisture, so the chitin in the fiber sponge material is not decomposed before use. When a fibrous sponge material is used for treatment, the dressing absorbs moisture from the wound, thereby restoring the activity of the chitin enzyme and starting to decompose chitin. In one embodiment, the chitin degrading enzyme is added in an amount of 1 to 20 U.

In one embodiment, step 110 further comprises adding 0.68 to 3 parts by weight of a crosslinking agent to mix in water to form a composite fiber liquid. The crosslinking agent can be a crosslinking agent having a divalent ion such as calcium chloride (CaCl ₂ ).

The method of making a fibrous sponge dressing of the present invention may additionally add a functional ingredient to the water in step 110 to form a composite fiber liquid. For example, the addition of silver can impart an antibacterial effect to the prepared fibrous sponge material, or the addition of a growth factor can enhance the wound healing effect of the prepared fiber sponge material.

The fiber sponge material is formed by freeze-drying a composite fiber liquid containing chitin fiber and poly(lactic acid-glycolic acid) copolymer fiber, and the fiber sponge material has a sponge fiber in which two fibers are interlaced. structure. In one embodiment, the fibrous sponge material is a fibrous sponge material that simulates a cortical structure.

The fiber sponge material of the present invention has a sponge-like fiber structure which is composed of two kinds of fibers of chitin fiber and poly(lactic acid-glycolic acid) copolymer fiber, and a sponge having a plurality of holes is formed by the interlaced fibers. Structure. The fiber sponge material of the invention has a biodegradation time course of about 1 to 3 months, and is gradient degradation during the treatment of the wound, so that the new cell/tissue is more intact, which is beneficial to tissue regeneration and wound healing. The appearance is relatively flat and uniform. In addition, the fibrous sponge dressing of the present invention is suitable for treating deep wounds with a long healing time, such as acne and deep diabetic wounds, due to the long biodegradation time course. In addition, the raw material cost of chitin and poly(lactic acid-glycolic acid) copolymer is relatively low, and the unit price of the pharmaceutical grade poly(lactic acid-glycolic acid) copolymer is about 1/10 to 1/100 of the unit price of pharmaceutical grade collagen. . Compared with the conventional collagen sponge material, the fiber sponge material of the invention has the advantages of low cost, no need to repeatedly change the dressing, and reduce scar generation.

The following examples are given to illustrate the method of the present invention in more detail, and are intended to be illustrative only and not to limit the invention, and the scope of the invention is defined by the scope of the appended claims.

Experimental example 1, structural stability test

In this experimental example, the stability of the structure of the fibrous sponge material of the examples and the comparative examples was tested. The structural stability test method was to observe whether the structure of the sample was broken after immersing the sample in secondary water at 37 ° C overnight. The test results are shown in Table 1 below.

The method for producing a fibrous sponge material of the present experimental example comprises the following steps:

1. Mixing chitin fiber, poly(lactic acid-glycolic acid) copolymer fiber, hyaluronic acid, and alginic acid and a crosslinking agent in secondary water to form a composite fiber liquid. In this embodiment, the molecular weight of the chitin fiber is 18,560 Da, the molecular weight of the poly(lactic-glycolic acid) copolymer fiber is 56,241 Da, the copolymerization ratio is 75:25, and the crosslinking agent is calcium chloride (CaCl _{2 ).} ).

2. The composite fiber liquid of the step 1 was freeze-dried to form the fiber sponge material of Examples 1 to 7. For the composition ratio of each example, refer to Table 1, in which the PLGA fiber system represents a poly(lactic acid-glycolic acid) copolymer fiber.

The fiber sponge material to which no alginic acid and a crosslinking agent were added was used as Comparative Example 1, and the composition ratio thereof is shown in Table 1.

It is worth noting that the fiber sponge material used in this experimental example was not added with chitin degrading enzyme in order to avoid the test of structural stability, the chitin in the fiber sponge material was decomposed and affected the test. result.

As a result of the structural stability test, the composition of each component of the fiber sponge material of Example 2 was suitable for molding. Taking the composition ratio of each component of Example 2, and using different poly(lactic-glycolic acid) copolymer fibers and different chitin decomposing enzymes to prepare different specifications of Examples 2-1 to 2-5. The fiber structure sponge material is subjected to subsequent experimental examples, and the composition ratio thereof is shown in Table 2. The poly(lactic-glycolic acid) copolymer fibers used in Examples 2-1 to 2-4 had a molecular weight of 56,241 Da and a copolymerization ratio of 75:25. The poly(lactic-glycolic acid) copolymer fiber used in Example 2-5 had a molecular weight of 14,145 Da and a copolymerization ratio of 75:25. The chitin fibers used in Examples 2-1 to 2-5 had a molecular weight of 18,560 Da.

The preparation methods of Examples 2-1 to 2-5 were similar to those of Example 2 except that a chitin degrading enzyme was additionally added in the step 1 to form a composite fiber liquid.

As a comparative example 2, a hyaluronic acid sponge material to which no chitin fiber, poly(lactic acid-glycolic acid) copolymer fiber, alginic acid and a crosslinking agent were added; no chitin fiber, poly(lactic acid-glycolic acid) Copolymer fiber and hyaluronic acid seaweed sponge sponge as Comparative Example 3; and hyaluronic acid/seaweed composite sponge material without adding chitin fiber and poly(lactic acid-glycolic acid) copolymer fiber as a comparison For example 4, please refer to Table 2 for the composition ratio. In addition, a BIOSTEP ^® collagen sponge material sold by Smith & Nephew Co., Ltd. was used as Comparative Example 5 for subsequent experiments.

Experimental example 2, swelling ratio test

In this experimental example, the swelling ratio test of the examples and the comparative examples in physiological saline was carried out by the test method of EN13726-1:2002, and the results are recorded in Table 3 below.

As can be seen from the results of Table 3, the swelling ratio of the examples was about 13 to 16 times, which was superior to the commercially available product BIOSTEP ^® (8.74 times).

Experimental Example 3, in vitro degradation test

In this experimental example, in vitro degradation tests ( in vitro ) were carried out on the examples and comparative examples using the test method of ASTM F1635-04a. Please refer to FIG. 4 , which is a diagram showing the degradation rate-time relationship between the embodiment of the present invention and the comparative example, wherein the lines 210, 220, 230, 240, 250, 260, and 270 represent the comparative example 5 and the comparative example 4, respectively. The results of Example 2-1, Example 2-2, Example 2-3, Example 2-4, and Example 2-5. As can be seen from Fig. 4, the time required for the material to degrade by 90 wt% is: Comparative Example 5 (BIOSTEP ^® ) for about 5 days; Comparative Example 4 for about 10 days; Example 2-1 for more than 90 days; Example 2-2 for about 84 Days; Example 2-3 for about 70 days; Examples 2-4 for about 42 days; and Examples 2-5 for about 28 days. Therefore, the degradation rate of the fibrous sponge material of the present invention can be regulated by adjusting the copolymerization ratio and molecular weight of the poly(lactic-glycolic acid) copolymer, the content of the chitin degrading enzyme, and the composition and ratio of the dressing.

Experimental example 4, implant degradation test

In this experimental example, the examples and comparative examples were subjected to an implant degradation test ( in vivo ) using the test method of ISO 10993-6, the sample was implanted under the skin of the rat, and the time required for the sample to be degraded was observed.

On the 7th day after the material of Comparative Example 5 was implanted into the skin of rats, the implant was unable to observe the implant. The material of Comparative Example 4 was observed on the 7th day after implantation, but no implant was observed on the 30th day after implantation. The implant of Example 2-1 was observed on the 7th, 30th, and 90th day after implantation, and the appearance of the dressing gradually decreased over time. A portion of the implant was observed after the 7th and 30th days of the dressing of Examples 2-4, and the appearance of the dressing gradually decreased over time; the implant was no longer observed on the 90th day of the rat tissue appearance. A portion of the implant was observed after the 7th and 30th days of the dressing of Examples 2-5, and the appearance of the dressing gradually decreased over time; the implant was no longer observable on the 90th day after implantation. The results of this experimental example show that, in accordance with the trend of in vitro degradation, the fiber sponge material of the present invention can be controlled to decompose in a physiological environment (for example, subcutaneously) in the range of about 1 to 3 months.

Experimental Example 5: Comprehensive evaluation of wound healing

This experimental example uses deep wounds of diabetic pigs to evaluate the effect of the dressings of the examples and comparative examples on wound healing. In the experimental manner, the dressing materials of Comparative Example 5, Example 2-2, Example 2-4 or Example 2-5 were placed on the wound, and the outer layer of the dressing of the comparative example or the example was covered with moisturizing or antibacterial coating. The material keeps the inner layer of material moist and observes the appearance of the wound and the rate of healing. It is worth noting that since Comparative Example 5 was completely degraded within a few days, it was timed to replace or supplement. Moisturizing or antibacterial dressings such as medical gauze, AQUACEL ^® Ag sold by Conva tec, etc., need to be replaced regularly. In Comparative Example 5 the inner cladding material, and the outer covering AQUACEL ^® Ag as Comparative Example 5-1, and Comparative Examples 5 to apply an inner layer material, the outer covering of medical gauze and Comparative Example 5-2. The outer layer of Example 2-2 covered AQUACEL ^® Ag, while the outer layers of Examples 2-4 and Examples 2-5 covered the moisturizing dressing.

Please refer to FIG. 5 , which is a graph showing the wound healing rate-time relationship between the examples and the comparative examples, wherein the lines 310, 320, 330, 340 and 350 represent the comparative example 5-1 and the comparative example 5-2, respectively. The results of Example 2-2, Example 2-4 and Example 2-5. As can be seen from Fig. 5, the time required for the wound to heal 80% is: Comparative Example 5-1 about 25 days; Comparative Example 5-2 about 26 days; Example 2-2 about 19 days (Compared with Comparative Example 5-1 24) %); Example 2-4 was about 19 days (24% shorter than Comparative Example 5-1); and Example 2-5 was about 17.5 days (30% shorter than Comparative Example 5-1). The healing time of the examples (80% healing of the wound) was shortened by about 24 to 30% compared to the commercially available standard product BIOSTEP ^® (Comparative Example 5-1). In addition, since the wound treated by the comparative example 5 needs to be replaced or supplemented with the inner layer, the wound healing is slow, the tissue regeneration structure is uneven, and scarring is easy. In addition, since the inner and outer layers of the comparative examples need to be replaced frequently, the overall treatment cost is high. After the treatment with the fiber sponge material of the embodiment, the wound healing is moist and flat, and the tissue regeneration structure is relatively uniform, so that the scar can be reduced. In addition, only the outer layer of the material has to be replaced during the treatment, so the economic cost is low.

The results of the foregoing Experimental Examples 3 to 5 are summarized in the following Table 4, wherein the experimental three series test the time required for the composite of the comparative example and the example to degrade 90 wr% in vitro; the experimental example four series test comparative examples and examples The material is large The time required for subcutaneous degradation of the mouse; Experimental Example Five tests the time required for the wound to heal 80% of the wound of the comparative example and the example, and observes the appearance of the healing tissue after the treatment.

As can be seen from the results of Table 4, the fibrous sponge material of the present invention has a long biodegradation time course (about 1 to 3 months) both in vitro and in vivo. In addition, the wound treated by the fiber sponge material of the present invention has a faster healing speed, and the wound tissue is more even and uniform in appearance, and is less likely to cause scarring.

In summary, the fiber sponge material of the present invention comprises a sponge-like composite of chitin fibers and poly(lactic acid-glycolic acid) copolymer fibers. Fiber structure and polysaccharide. The spongy fibrous structure forms a structure having a plurality of pores by interlaced fibers to enhance the structural stability of the fibrous sponge material and to induce tissue regeneration as a scaffold for cell growth. The polysaccharide system enhances the biocompatibility and healing function of the fibrous sponge material, and causes the fibrous sponge material to exhibit a gradient degradation during the treatment of the wound, thereby providing a suitable growth environment and tissue regeneration space for the regenerated cells, and The appearance of the wound after healing is relatively flat and uniform. In addition, since the biodegradation time course is long (about 1 to 3 months), the fiber sponge material of the present invention is suitable for treating deep wounds having a long healing time. Compared with the conventional collagen sponge material, the fiber sponge material of the invention has the advantages of low cost, convenient use (no need to repeatedly change the dressing) and reduction of scar generation. In addition, the method for producing a fibrous sponge material of the present invention is to obtain a fiber sponge material by freeze-drying a composite fiber liquid containing various components, and the process is simple.

Although the present invention has been disclosed in the above embodiments, it is not intended to limit the present invention, and the present invention can be modified and modified without departing from the spirit and scope of the present invention. The scope is subject to the definition of the scope of the patent application attached.

Claims (18)

A fiber sponge material comprising: a sponge-like fiber structure comprising: chitin fiber, 3 parts by weight; and poly(lactic acid-glycolic acid) copolymer fiber, 1 to 9 parts by weight; a polysaccharide body, Dispersing in the sponge-like fibrous structure, and occupying 1.33 to 20 parts by weight; a crosslinking agent, accounting for 0.68 to 3 parts by weight; and a chitin degrading enzyme dispersed in the sponge-like fibrous structure, wherein the chitin The content of the decomposing enzyme is 1 to 100 U, wherein 1 U represents the enzyme required for the chitin to decompose chitin and release 1.0 mg of N -acetylglucosamine at a pH of 6.0 and a temperature of 25 ° C. the amount. The fibrous sponge material of claim 1, wherein the chitin has a crystallinity of less than 5%. The fibrous sponge material according to claim 1, wherein the chitin has a molecular weight of 5 to 100 kDa. The fibrous sponge material of claim 1, wherein the chitin has a degree of deacetylation greater than 95%. The fiber sponge material according to claim 1, wherein the poly(lactic acid-glycolic acid) copolymer has a copolymerization ratio of lactic acid to glycolic acid of 50:50 to 75:25. The fiber sponge material according to claim 1, wherein the poly(lactic acid-glycolic acid) copolymer has a molecular weight of 5 to 100 kDa. The fiber sponge material according to claim 1, wherein the chitin fiber and the poly(lactic acid-glycolic acid) copolymer fiber have a diameter of 1 to 20 μm. The fibrous sponge material of claim 1, wherein the polysaccharide comprises hyaluronic acid and alginic acid. The fiber sponge material according to claim 8, wherein the hyaluronic acid accounts for 0.8 to 12 parts by weight, and the alginic acid accounts for 0.53 to 8 parts by weight. The fiber sponge material according to claim 1, wherein the content of the chitin degrading enzyme is 1 to 20 U. The fiber sponge material according to claim 1, wherein the fiber sponge material has a basis weight of 100 to 300 g/m. The fiber sponge material according to claim 1, wherein the fiber sponge material has a thickness of 0.5 to 20 mm. The fiber sponge material according to claim 1, wherein the fiber sponge material is a fiber sponge material of a simulated skin structure. A method for producing a fiber sponge material, comprising: 3 parts by weight of chitin fiber, 1 to 9 parts by weight of poly(lactic acid-glycolic acid) copolymer fiber, 1.33 to 20 parts by weight of a polysaccharide, and a crosslinking agent 0.68~3 parts by weight and one chitin decomposing enzyme 1~100U are mixed in water to form a composite fiber liquid, wherein 1U represents the pH of 6.0 and the temperature is 25 ° C, the chitin decomposing enzyme decomposes chitin in one hour. An amount of the enzyme required to release 1.0 mg of N -acetylglucosamine; and freeze-drying the composite fiber solution to form the fiber sponge material, wherein the chitin fiber is copolymerized with the poly(lactic acid-glycolic acid) The fibrous fiber forms a sponge-like fibrous structure of the fibrous sponge material, and the polysaccharide and the chitin degrading enzyme are dispersed in the sponge-like fibrous structure. The method of claim 14, wherein the polysaccharide comprises hyaluronic acid and alginic acid. The method of claim 15, wherein the hyaluronic acid comprises 0.8 to 12 parts by weight, and the alginic acid accounts for 0.53 to 8 parts by weight. The method of claim 14, wherein the chitin degrading enzyme is added in an amount of 1 to 20 U. The method of claim 14, wherein the fibrous sponge material is a fibrous sponge material of a simulated cortical structure.