TWI477670B - Micro-fibrous hemostatic materials and methods for preparing the same - Google Patents

Description

Micron-sized fibrous hemostasis material and preparation method thereof

The invention relates to a hemostatic material and a preparation method thereof, and in particular to a micron-scale fibrous hemostatic material and a preparation method thereof.

Blood loss is one of the most important causes of human death. It is estimated that about 50% of people die from a lot of blood loss. The amount of blood in the human body is about 1/13 of that of body weight. When the blood loses more than 15% in the body, shock occurs. If it exceeds 30%, it will be life-threatening. Therefore, it is necessary to be able to stop bleeding in a timely and effective manner in order to stabilize the injury and thereby create favorable conditions for subsequent treatment.

In order to effectively stop bleeding, hemostatic dressings are often used in current hemostasis procedures. Chitosan is one of the main components of current hemostatic dressings. The positively charged chitosan material itself has no adhesion ability, but when it encounters blood, it will combine with negatively charged red blood cells, platelets, white blood cells, etc. Cell emboli (or thrombus) seals the hemorrhage and forms a barrier that not only stops bleeding, but also reduces the chance of infection by bacteria and other invaders.

Currently there are a variety of commercially available hemostatic dressing as CELOX ^TM (SAM Medical Products Ltd.) and (HEMCON, Inc. production) hemostatic powder and the like. However, the anti-solubility of these hemostatic powders is not ideal, and after contact with blood, the powder dissolves quickly to form a hydrogel. When used in a large number of bleeding wounds, such hydrogels are easily washed away by the blood; therefore, it is usually necessary to use a large amount of hemostatic powder to achieve the purpose of stopping bleeding. In order to solve this problem, the support substrate may be additionally applied to prevent the gel from being carried away by the blood; or the prepared hemostatic material may be further compressed to increase the density of the material and thereby retard the dissolution rate of the material. However, the above methods require the use of additional materials or steps, thereby increasing the cost and/or time cost of preparing the hemostatic material.

Therefore, how to improve the anti-solubility of the hemostatic dressing and reduce the clotting time by using a simple method is still one of the research and development centers in related fields.

SUMMARY OF THE INVENTION The Summary of the Disclosure is intended to provide a basic understanding of the present disclosure. This Summary is not an extensive overview of the disclosure, and is not intended to be an

One aspect of the present invention relates to a method for preparing a hemostatic material, which can be prepared by using any suitable method of chitosan fiber, and then acidifying the fiber to form a fibrous hemostatic material. It's simpler.

According to an embodiment of the invention, the above preparation method comprises the following steps. The chitosan fiber having a fiber diameter of about 10 to 100 μm is immersed in an acid solution (or acidification solution) of about 3 to 60 wt% to acidify the surface of the chitosan fiber. The acidified chitosan fiber is powdered to obtain a fibrous powder of chitosan having a length of less than about 1 mm.

Another aspect of the present invention relates to a micron-sized fibrous hemostatic material which does not have significant biological toxicity and has desirable coagulation efficacy and solubility resistance, is suitable for treating various wounds, and is particularly suitable for wounds with massive bleeding. .

According to an embodiment of the invention, the micron-sized fibrous hemostatic material comprises a fibrous powder of a partially acidified chitosan having a fiber diameter of about 10 to 100 μm and a length of less than about 1 mm.

The basic spirit and other objects of the present invention, as well as the technical means and implementations of the present invention, will be readily apparent to those skilled in the art of the invention.

The description of the embodiments of the present invention is intended to be illustrative and not restrictive. The features of various specific embodiments, as well as the method steps and sequences thereof, are constructed and manipulated in the embodiments. However, other specific embodiments may be utilized to achieve the same or equivalent function and sequence of steps.

According to an embodiment of the present invention, a method for preparing a micron-sized fibrous hemostatic material comprises: acidifying and then pulverizing an appropriate chitosan fiber to obtain a micron-sized fibrous hemostatic material.

The test results show that the diameter of the chitosan fiber affects the hemostatic effect of the hemostatic material. When the fiber diameter is less than 10 μm, the hemostatic effect and the anti-blood solubility are very unsatisfactory; in addition, if the diameter of the chitosan fiber is too large, application to the wound may cause the patient to be uncomfortable. Therefore, according to an embodiment of the present invention, chitosan fibers having a fiber diameter of about 10 to 100 μm should be obtained first, and preferably have a fiber diameter of about 10 to 20 μm. In particular, the fibers may have a diameter of about 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 μm.

In accordance with the principles and spirit of the present invention, any conventional technique can be utilized to prepare chitosan fibers suitable for use in the present process; for example, wet spinning techniques can be utilized to prepare the chitosan fibers described above.

According to an optional embodiment, the preparation of the chitosan fiber by wet spinning comprises the steps of:

(1) dissolving chitosan in an aqueous solution of acetic acid to prepare a spinning solution;

(2) dissolving an aqueous sodium hydroxide solution in a hydrophilic solvent and water having a volume ratio of about 1:1 to prepare a molding liquid;

(3) Using a wet spinning apparatus, the spinning solution is passed through a molding liquid to prepare chitosan fibers having a fiber diameter of about 10 to 100 μm.

In the spinning solution, the concentration of chitosan is about 3-8 wt%; specifically, the concentration can be about 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5 or 8 wt%. Further, the concentration of acetic acid in the spinning solution is about 3-10 wt%; such as 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 wt%.

In general, chitosan is obtained by deacetylation of chitin. According to an optional embodiment of the present invention, the chitosan used has a degree of deacetylation of about 50-99%; For example, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98 or 99%.

In the molding liquid, the concentration of sodium hydroxide is about 3-10 wt%, such as 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 or 10 wt%. .

Further, the hydrophilic solvent used in the molding liquid may be methanol, ethanol, water, acetone or a mixed solvent of at least two of them.

By way of illustration and not limitation, in an optional embodiment, the concentration of acetic acid in the spinning solution is about 5% by weight, the oxime of chitosan is about 90%, and the concentration is about 5% by weight; Methanol and water in a volume ratio of about 1:1 were used, and the concentration of sodium hydroxide was about 5% by weight.

In a preferred embodiment, the resulting chitosan fibers can be rinsed with deionized water after step (3) to wash away residual base.

After obtaining appropriate chitosan fibers (fiber diameters of about 10-100 μm), they are immersed in an acid ethanol solution to acidify the surface of the chitosan fibers.

In the examples of the present invention, an organic acid or a mineral acid may be used to prepare an ethanol solution of the above acid. Examples of organic acids include, but are not limited to, acetic acid, lactic acid, citric acid, succinic acid, malic acid, maleic acid, and acrylic acid; and examples of inorganic acids include, but are not limited to, hydrochloric acid and sulfuric acid.

In the above acid ethanol solution, the weight percentage of the acid is about 3 to 60 wt%; preferably about 5 to 20 wt%, such as about 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 or 60 wt%.

Generally, the time of soaking depends on the type of acid used, the concentration, and the degree of acidification. However, the degree of acidification of the material is not easily quantified; therefore, in the present invention, the acidification of the material is illustrated by the process conditions and the effects exhibited by the product.

By way of illustration and not limitation, when chitosan is immersed in acetic acid at a concentration of about 3-60 wt%, a hemostatic material (resistance to solubility) which combines desirable solubility and coagulation efficacy can be obtained in about 10-180 minutes. The analysis of coagulation efficacy is detailed below. Specifically, the above immersion time may be about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175 or 180 minutes.

In contrast, if other conventional process conditions are the same, if the conventional chitosan powder is soaked in the acidification solution, the solubility and coagulation properties of the material cannot be effectively improved.

After the soaking is completed, the chitosan fibers can be taken out and dried. For example, chitosan fibers can be placed in an oven and dried at a temperature of about 40-70 °C.

Thereafter, the acidified chitosan fiber is powdered to obtain a fibrous powder having a length of less than about 1 mm of chitosan. In general, if the length of the fibrous powder is too long, it may cause discomfort to the patient when used on the wound, and may be stuck on the wound and is not easily removed; therefore, in the embodiment of the present invention, the fibrous shape is used. The length of the powder is limited to 1 mm or less. However, it has been found during the test that when the length of the fibrous powder is too small, the solubility resistance and coagulation efficiency of the fibrous powder may be greatly impaired; therefore, in an alternative embodiment of the present invention, the length of the fibrous powder is It is defined as from about 10 μm to about 1 mm, and the preferred fibrous powder has a length of from about 100 to 500 μm.

This pulverization step can be carried out using any suitable equipment. For example, chitosan fibers can be placed in a high speed homogenizer and agitated, mixed, dispersed and sheared by a high speed homogenizer to obtain a fibrous powder.

The test results show that the fibrous powder of chitosan which is not significantly cytotoxic can be obtained according to the above steps; in other words, the material can be directly applied to the animal as a hemostatic material without an additional treatment step.

According to a specific embodiment of the present invention, a micron-sized fibrous hemostatic material comprising a fibrous powder having a partially acidified chitosan surface having a fiber diameter of about 10 to 100 μm and a length of less than about can be obtained by the above method. 1 mm. Test results show that such micron-sized fibrous hemostatic materials are suitable for treating various wounds; and because of their better resistance to dissolution, they are particularly suitable for large bleeding wounds.

Specifically, during the hemostasis process, when the micron-sized fibrous hemostatic material is in contact with blood, a portion of the fibrous hemostatic material interacts with various molecules in the blood to produce a massive gel; however, other Part of the fibrous hemostatic material still retains the original fibrous structure and thus forms a fiber-clot structure.

The fiber-clot structure is generally a network structure in which the original fibrous materials are joined together by a gel. This fiber-clot structure can block the wound to achieve a coagulation effect; in addition, the test results show that the absorbed blood is encapsulated in the gel and does not easily bleed out. Furthermore, compared with the gel structure produced by some traditional hemostatic materials after encountering blood, the reticulated fiber-clot structure is better in solubility; that is, the reticulated fiber-clot structure It is less likely to be dissolved (or rushed) by the blood, and thus the stagnation time of the hemostatic material of the present invention at the wound can be improved, thereby improving the blood coagulation effect.

Since the micron-sized fibrous hemostatic material proposed herein first contacts the blood, a fibrous fiber-clot structure is formed, and the fibrous hemostatic material can be used without using an additional supporting substrate. The time spent at the wound is sufficient to effectively stop the bleeding of the wound.

In order to verify the anti-dissolution properties and coagulation potency of the micron-sized fibrous hemostatic material proposed herein, different fibrous hemostatic materials were prepared according to the method set forth in the above examples of the present invention, and their anti-dissolution properties and coagulation efficacy were analyzed. Table 1 below summarizes the partial process conditions used in each of the experimental examples, as well as the anti-solubility and coagulation efficacy (including hemostasis time and aspiration rate) of each hemostatic material.

Taking Experimental Example 1A as an example, the preparation method is to soak a chitosan fiber having a diameter of about 10-20 μm in a solution of about 5 wt% of acetic acid in ethanol for about 30 minutes. Thereafter, the chitosan fiber is filtered and dried, and then the chitosan fiber is pulverized by a high-speed homogenizer (Model: RT02; Lingguang Industrial Co., Ltd.) to obtain the micron scale of Experimental Example 1. A fibrous hemostatic material having a micron-sized fibrous hemostatic material having a length of about 10-100 μm and having an appearance as shown in the scanning electron micrograph (SEM) photograph of Fig. 1. The preparations of Experimental Examples 2A to 8A shown in Table 1 were substantially the same as those of Experimental Example 1, and only the concentration of the ethanol solution of acetic acid was changed. Further, Experimental Examples 1B to 8B were immersed in chitosan fibers in different concentrations of succinic acid in ethanol.

In Comparative Examples 1 to 8, commercially available chitosan powder (Shizhan Technology Co., Ltd.) was separately immersed in a solution of different concentrations of succinic acid in ethanol for 30 minutes.

In Experimental Examples 9A and 9B, chitosan fibers were respectively immersed in a 3 wt% ethanol solution of acetic acid and a solution of succinic acid in ethanol for a period of up to 5 hours. In Comparative Example 9, the above commercially available chitosan powder was immersed in a 3 wt% ethanol solution of succinic acid, and the soaking time was also 5 hours.

Further, also commercially available hemostatic powder CELOX ^TM (the unsealing process without additional acidification, then display packaging, this material has been soaked in the preparation of acid solution) was subjected to the same test as a reference. Above CELOX ^TM hemostatic powder irregular appearance of tabular grains having a size between about 100-900 μm.

After obtaining the hemostatic materials of various experimental examples and comparative examples, the following methods were used to evaluate the anti-solubility and hemostatic efficacy of each material.

Since the blood contains about 50% or more of water, about 1 g of hemostatic material and about 35 mL of physiological saline are placed in the vial during the anti-solubility test, and then the sample bottle is shaken with an oscillator and started. Timing. This time is the time required to dissolve the hemostatic material when it is not visible to the naked eye that there is a significant deposit of hemostatic material in the vial.

2A and 2B, respectively, of FIG. 2A is a hemostatic material of Experimental Example CELOX ^TM hemostasis and appearance at the time of completion of the test powder. It can be seen from Figure 2A that after about 30 minutes of shaking, there is still a considerable deposit at the bottom of the vial, which is the fiber-clot structure described herein. It is estimated that in Experimental Example 2, about 42% of the hemostatic material dissolved to form a hydrogel, and the remaining portion remained in the fiber-clot structure in the form of a fibrous material. In the Figure 2B, after about 124 seconds, the bottom of the sample bottle is almost no existence of the precipitate was found at this time CELOX ^TM hemostatic powder had fully dissolved to form a gel and suspended in physiological saline.

In terms of the solubility resistance of the material alone, the longer the dissolution time, the better the solubility resistance of the material. The un-acidified chitosan material (eg, blank or blank) will hardly dissolve under the test conditions; that is, the material will still exhibit the original fibrous or powdery appearance after prolonged shaking. . However, the coagulation performance of such an unacidified chitosan material is not ideal (see below for details).

From the results shown in Table 1, it was found that the dissolution time of the material of the experimental example of the present invention was more than 30 minutes when the acid concentration in the acidified solution was about 3 wt% (see Experimental Examples 1A, 1B, 9A and 9B). In addition, as the concentration of the acid in the acidified solution is gradually increased, the dissolution time is slightly lowered. However, even when the acid concentration in the acidifying solution was as high as about 60%, the dissolution time of the experimental material of the present invention was still higher than 16 minutes (see Experimental Examples 8A, 8B). In contrast, commercially available chitosan powders exhibit anti-dissolution properties under the same test conditions only when the acid concentration in the acidified solution is less than 5 wt% (see Comparative Examples 1, 2, 2. 9); When the acid concentration in the acidification solution is higher than 10 wt%, the dissolution time is only about 10 minutes (see Comparative Example 3), and when the acid concentration in the acidification solution is further increased, the solubility resistance thereof It will be greatly reduced (see Comparative Example 4-8, the dissolution time of the material is reduced from about 6 minutes to less than 1 minute).

Further, it can be seen from the results shown in Table I and Figure 2, a commercially available hemostatic powder CELOX ^TM enough for solvent resistance, under the test conditions, about 2 minutes would have been substantially dissolved to form a gel.

In the part of coagulation efficacy, the Lee-White's Method is used to determine the hemostasis time (blood coagulation time) of the sample; and an ELISA test is used to test whether the hemostatic material can fix the blood.

According to the Lee-Bai's method, about 0.5 g of hemostatic material and about 3.5 ml of blood (containing anticoagulant-hepatic anticoagulant) are added to the sample bottle, and then the cap is locked and placed in the shaker. The middle and lower oscillating, observing whether the blood in the bottle flows, and stopping the flow, is the hemostasis time of the sample material.

From the results shown in Table 1, it can be found that when the butanose material is not acidified, its coagulation efficiency is not ideal. Under the test conditions, it takes more than 30 minutes to stop bleeding (please see blank experiment, blank) Comparative example). In contrast, the micron-sized fibrous hemostatic material of Experimental Examples 1A to 9A of the present invention has a hemostasis time of about 19 to 65 seconds under test conditions, and a preferred hemostasis time is about 19 to 31 seconds. Further, the micron-sized fibrous hemostatic material of Experimental Examples 1B to 9B of the present invention had a hemostasis time of about 43 to 108 seconds under the test conditions.

As for the materials of Comparative Examples 1-9, the hemostasis time was about 62 seconds to 30 minutes or more. Further, a commercially available hemostatic powder CELOX ^TM of the measured under the same test conditions hemostasis processing time of about 65 seconds.

Looking at the dissolution time and hemostasis time in each experimental example and the control example, it can be found that the acid concentration in the acidified solution plays a key role in the solubility resistance and coagulation efficiency of the material; that is, as the acid concentration increases, although Shorten the hemostasis time of the material, but at the same time reduce the resistance of the material. However, an ideal hemostatic material should have both good resistance to dissolution and short hemostatic time.

Taking Comparative Example 8 as an example, the commercially available chitosan powder was immersed in a solution of about 60 wt% succinic acid/ethanol, although the hemostasis time of the material was greatly reduced from 30 minutes or more (blank experimental example) to about 62. Second; however, its dissolution time is greatly reduced to about 57 seconds. If this material is actually used for hemostasis, these materials may have dissolved before the effective hemostasis, and it is difficult to exert the actual hemostatic effect.

The preparation method proposed by the present invention solves the problem of the concentration of acid in the acidified solution and the two characteristics.

From the results of Table 1 and the above discussion, it was found that when the commercially available chitosan powder was acidified under the same conditions, a hemostatic material which satisfies both the solubility resistance and the coagulation efficiency cannot be obtained.

However, the inventors used the chitosan fibers proposed herein with a suitable concentration of acidifying solution, but unexpectedly obtained a fibrous hemostatic material which has both anti-dissolution properties and coagulation properties, and the material can be coagulated in a short period of time. The blood can stay in the wound for a long time at the same time, so it is also suitable for a large number of bleeding wounds.

In the liquid absorption test, a hemostatic material with a dry weight of about 1 g was placed in a sample vial and about 100 mL of physiological saline was added, and placed on a shaker for about 5 minutes to allow the hemostatic material to have sufficient time to absorb the water. . Then, a filter paper having a pore size of 5 μm is used to retain a component having a particle diameter of more than 5 μm, and the weight is weighed, which is the aspiration weight of the sample. Then calculate the liquid absorption ratio of each hemostatic material according to the following formula:

Aspiration rate (%) = (absorbent weight / dry weight) × 100%.

As it can be seen from the table a, CELOX ^TM hemostatic powder almost no absorbent capacity. In contrast, the micron-sized fibrous hemostatic material proposed herein has a very good liquid absorbing ability and can absorb more than 4 times its own weight under the test conditions. This ideal liquid absorbing capacity also makes the micron-sized fibrous hemostatic material proposed herein suitable for treating large numbers of bleeding wounds.

In addition, in order to further confirm whether the micro-fibrous fibrous hemostatic material proposed herein is in contact with blood, whether the formed fiber-clot structure can effectively fix the blood therein without being precipitated, also for Experimental Example 2A haemostatic material commercially available hemostatic powder were CELOX ^TM by ELISA.

The steps of the ELISA assay are as follows. First, about 0.5 g of hemostatic material is contacted with about 3.5 mL of whole blood and allowed to stand for about 90 seconds to facilitate the hemostatic material to absorb blood and exert a coagulation effect. Thereafter, about 20 ml of physiological saline was added to the sample, and then the physiological saline solution was measured for light having a wavelength of 540 nm after shaking with an oscillator of about 0 (no oscillation), 1, 2, 3, 5, and 10 minutes, respectively. The optical density (OD) of the reference wavelength of 650 nm is used to determine the coagulation efficiency of the test substance. In general, the better the coagulation efficiency of the material, the blood is less likely to be released into the physiological saline solution, then the sample will have a lower absorption for light with a wavelength of 540 nm. Table 2 shows that compared to only 3.5 mL of whole blood. (The OD value is set to 1) The OD value of each hemostatic material.

As can be seen from Table 2, after 10 minutes of shaking, the OD value in the sample of Experimental Example 2A was about 0.005, that is, about 99.5% or more of the blood was encapsulated in the gel without oozing out. In contrast, CELOX ^TM styptic powder in 90 seconds after contact with blood, even in the case without a shock, there is no way to effectively fix the blood. Blood fixing performance micron fibrous hemostatic material embodiment proposed can be seen in the embodiment of the present invention is superior to commercially available CELOX ^TM hemostatic powder.

Without limiting the invention to a particular theory, the inventors believe that the fiber-clot structure produced by the hemostatic material of the embodiment of the present invention after blood-sucking helps to immobilize blood therein without precipitation.

Since the primary use of the micron-sized fibrous hemostatic material proposed herein is to stop bleeding, the resulting material cannot have significant cytotoxicity, which would otherwise cause the cells at the wound to die. Therefore, the cell viability of the micron-sized fibrous hemostatic material of Experimental Example 2A and fibroblasts (L-929) co-cultured for 24 hours was analyzed according to the ISO 10993-5 standard. The test results showed that for the micron-sized fibrous hemostatic material of Experimental Example 2A, the cell viability under the material was about 85-90%; and the cell survival rate below the material boundary (0 line) was higher than 99%. It can be seen that the micron-sized fibrous hemostatic material prepared by the method according to the embodiment of the present invention has no significant cytotoxicity to the fibroblast, and thus the material is suitable as a hemostatic material for the animal body.

According to the principle and spirit of the present invention, various existing chitosan fibers can be selected, combined with the appropriate acidification solution concentration proposed herein, and then the acidified chitosan fiber is powdered; A fibrous powder of chitosan resistant to solubility and coagulation.

It is worth noting that, although the method used is not complicated, the inventors conducted a series of studies showing that by using the appropriate acidification solution concentration and matching the chitosan fiber proposed here, it is impossible to It is expected to obtain a fibrous hemostatic material which combines anti-dissolution properties with coagulation efficacy, and which can condense blood in a short period of time while remaining in the wound for a long time, and thus is also suitable for a large number of bleeding wounds.

Although the embodiments of the present invention are disclosed in the above embodiments, the present invention is not intended to limit the invention, and the present invention may be practiced without departing from the spirit and scope of the invention. Various changes and modifications may be made thereto, and the scope of the invention is defined by the scope of the appended claims.

The above and other objects, features, advantages and embodiments of the present invention will become more apparent and understood.

1 is a SEM photograph of a micron-sized fibrous hemostatic material according to an embodiment of the present invention;

Figs. 2A and 2B are photographs showing the appearance of the anti-solubility test of the experimental examples and the comparative examples of the present invention, respectively.

Claims (9)

A method for preparing a micron-sized fibrous hemostatic material comprises the steps of: immersing a chitosan fiber in an acid solution of an acid to acidify the surface of the chitosan fiber, wherein the acid is in the ethanol solution The concentration is about 3 to 60% by weight, and the fiber has a diameter of about 10 to 100 μm; the acidified chitosan fiber is powdered to obtain a fibrous powder of chitosan having a length of less than about 1 mm. The method of claim 1, wherein the chitosan fiber is produced by a wet spinning process, the wet spinning process comprising the steps of: preparing a spinning solution, which is a few The polysaccharide is dissolved in an aqueous solution of acetic acid, wherein the concentration of the chitosan in the spinning solution is about 3-8 wt%, and the concentration of the acetic acid in the spinning solution is about 3-10 wt%; The spinning solution is passed through a molding liquid comprising about 3 to 10% by weight of an aqueous sodium hydroxide solution dissolved in a hydrophilic solvent having a volume ratio of about 1:1 and water. The method of claim 2, wherein the chitosan has a degree of deacetylation of about 50-99%. The method of claim 2, wherein: the concentration of the acetic acid in the spinning solution is about 5% by weight; the concentration of the chitosan in the spinning solution is about 5% by weight; The concentration of the sodium hydroxide in the molding liquid was about 5% by weight. The method of claim 2, wherein the hydrophilic solvent is selected from the group consisting of methanol, ethanol, water, acetone, and combinations thereof. The method of claim 1, wherein the acid is hydrochloric acid, sulfuric acid, acetic acid, lactic acid, citric acid, succinic acid, malic acid, maleic acid or acrylic acid. The method of claim 1, wherein the acid is acetic acid, and the concentration in the ethanol solution is about 5-20% by weight. A micron-sized fibrous hemostatic material produced by the method according to any one of claims 1 to 7, comprising a fibrous powder having a partially acidified chitosan surface having a fiber diameter of about 10 -100 μm and less than about 1 mm in length. The micron-sized fibrous hemostatic material of claim 8 which forms a fiber-clot structure upon contact with blood.