KR102497989B1 - Hemostatic dressings - Google Patents

Abstract

The present invention provides a composition for hemostasis comprising a nanofiber form of cellulose (Cellulose Nanofiber Foam).
The novel hemostatic composition according to the present invention is well absorbed from the affected area, has excellent adhesiveness, does not cause an allergic reaction, and has excellent mechanical properties, water absorption, and formability.
In addition, the hemostatic dressing having an excellent hemostatic effect of the present invention has the advantage of excellent production efficiency as compared to conventional dressings that are manufactured in a simple process.

Description

Hemostatic dressings

The present invention relates to novel hemostatic dressings and applications thereof.

When the skin loses life protection functions such as preventing water loss, regulating body temperature, and preventing bacterial invasion due to various traumas, treatment of the affected area may be difficult or side effects may occur, and in severe cases, life may be lost. Hemostatic dressing products to solve these problems have the following limitations.

First, in the case of a cotton dressing, the exudate generated from the skin wound is not properly absorbed, and the unabsorbed secretion is adhered to the affected area, resulting in a difficult exchange.

Second, conventional gelatin sponges are excellent in absorbing exudate, but as absorption progresses, the volume of the sponge itself expands, which can cause side effects such as nerve damage.

Third, dressings containing conventionally known CNC (cellulose nanocrystal) foam have low aspect ratio and low structural stability because only crystalline parts exist, and to manufacture TEMPO CNC, the process is complicated, such as TEMPO treatment after strong acid treatment. There is a problem that is not suitable for mass production because the yield is low.

Finally, hemostatic dressings containing chitosan have been recently developed, and in this regard, Korean Patent Registration No. 10-1700107 discloses a chitosan-based hemostatic dressing composed of 100% chitosan, which may cause allergic reactions depending on the purity. However, since chitosan alone lacks adhesiveness, a separate additive or treatment process is required, so there are still many problems in practical use.

Under this background, the present inventors modified cellulose to have a carboxyl group at a certain ratio, and made it into nanofibers to prepare cellulose nanofibers, and these modified cellulose nanofibers have significantly higher hemostatic efficacy than existing chitosan hemostatic agents It was confirmed that the present invention was completed.

Republic of Korea Patent No. 10-1700107 (2017.01.20)

The present invention provides a novel composition for hemostasis, which absorbs exudates well in the affected area, has excellent adhesiveness, and does not cause allergic reactions.

In addition, the present invention provides a hemostatic dressing comprising the composition for hemostasis.

In addition, the present invention provides a method for preparing the composition for hemostasis.

In addition, the present invention provides a kit comprising a gastric hemostatic dressing.

In the present invention, cellulose nanofibers were used to develop a hemostatic dressing.

In the present invention, cellulose and/or cellulose nanofibers are stable by using plant-derived cellulose, unlike chitosan, which is an animal material and is likely to cause allergies. In addition, as a natural polymer manufactured using nano-crystallization technology, it has excellent biocompatibility, biodegradability, and excellent physical properties as a structure such as mechanical properties, water absorption, and formulation properties, so it can be suitably used as a hemostatic dressing. there is.

Moreover, in the case of chitosan used for medical purposes, it is very expensive because it is possible to express its function only when a product of high purity is used, whereas the hemostatic dressing based on cellulose nanofibers according to the present invention has a hemostatic effect higher than that of chitosan without containing chitosan as described above. can be displayed, resulting in significant savings in terms of cost.

In addition, since it is not cotton, non-woven fabric, polyurethane, etc., it has excellent biocompatibility and moisture absorption, and shows high hemostatic performance compared to conventional chitosan and chitin-containing products, etc., so it is easy to manufacture and use as a dressing without additional additives.

The present invention provides a composition for hemostasis comprising cellulose in the form of nanofibers.

The cellulose may be modified cellulose, preferably modified by TEMPO.

Typically, the surface of cellulose can be modified by oxidation with sulfuric acid, phosphoric acid, hydrochloric acid, nitric acid or TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical), but the modified cellulose of the present invention is Modified is most preferred. In this regard, compared to cellulose modified by sulfuric acid, phosphoric acid, hydrochloric acid, or nitric acid, cellulose modified by TEMPO contains both crystalline and amorphous regions and is flexible and structurally stable due to its high aspect ratio.

In particular, cellulose modified by TEMPO has high dispersibility due to the carboxy group having a negative charge, and since aggregation does not occur and the specific surface area is wide, the contact area with blood is wide, so that the hemostatic effect can be enhanced.

Cellulose in the form of nanofibers of the present invention may have an aspect ratio of 1/100 to 1/600, preferably 1/100 to 1/300.

In this regard, the conventional cellulose nanocrystal (CNC) has an aspect ratio of about 1/20 to 1/50, which is a short crystalline form compared to the nanofibrous cellulose of the present invention, and it is difficult to form a foam with cellulose nanocrystal alone. There is a problem with weak physical properties. Accordingly, in order to improve physical properties of the cellulose nanocrystal, an additive such as sodium alginate must be additionally mixed.

On the other hand, the nanofibrous cellulose of the present invention has an aspect ratio of 1/100 or more, and is a mixture of crystalline and amorphous forms, and the crystalline form is 40 to 70% of the total amount of the nanofibrous cellulose. there is. Due to these characteristics, the cellulose in the form of nanofibers of the present invention has a characteristic that can stably maintain physical properties even without additional additives (eg, sodium alginate).

In addition, the modified cellulose of the present invention may be one in which a carboxyl group is substituted at carbon number 6 of cellulose, and the cellulose has a surface modification rate of 1.2 to 2.5 mmol/g cellulose, preferably 1.5 to 2.0 mmol/g. It can be cellulose.

The hemostatic composition may further include a compound capable of generating sodium ions, potassium ions, magnesium ions, or calcium ions as a gelling aid. Preferably, the gelling aid is sodium chloride (NaCl), potassium chloride (KCl), magnesium chloride (MgCl ₂ ), calcium chloride (CaCl ₂ ), sodium hydroxide (NaOH), potassium hydroxide (KOH) and potassium carbonate (K ₂ CO ₃ ) may be selected from the group consisting of.

The composition for hemostasis of the present invention preferably has an excellent hemostatic effect while having a characteristic of stably maintaining the structure without additionally adding a gel reinforcing material such as sodium alginate.

In this regard, sodium alginate reacts with functional groups on the surface of cellulose to cause a cross-linking reaction, which causes a decrease in reactive sites with hemostatic effect. However, if a gel-reinforcing substance such as sodium alginate is not added, the reduction of this site does not occur, so excellent hemostatic effect can be exhibited.

In the present invention, the nanofibrous cellulose may have a diameter of 1 to 10 nm, preferably 3 to 8 nm, and when the diameter exceeds 10 nm, dispersibility decreases, resulting in aggregation or a decrease in surface area. Preference is given to using cellulose in the form of nanofibers having a diameter of less than nm.

In addition, the cellulose in the form of nanofibers of the present invention may have a length of 500 nm to 10 μm, preferably 500 nm to 3 μm.

In addition, the composition for hemostasis may include a different amount of cellulose in the form of nanofibers depending on the formulation. For example, it may be included in 0.1 wt% to 10 wt% at the time of hydrogel formulation, and may also be included at 0.1 wt% to 10 wt% when used as a coating agent. In the case of membrane, foam or sponge formulations, it may contain 10% or more.

The hemostatic composition may further include a hemostatic effect enhancing component. For example, enhancing hemostatic effect selected from the group consisting of thrombin, thromboplastin, fibrinogen, casein-kinase II, tissue factors, and combinations thereof components can be used.

In addition, the hemostatic composition may further include a gel-reinforcing material. This substance may be sodium alginate or gallic acid.

The present invention provides a dressing agent of a hydrogel formulation containing the composition for hemostasis.

The present invention also provides a dressing having a formulation of a membrane, sponge or foam containing a hemostatic composition.

The present invention also comprises the steps of (a) casting a gel comprising cellulose in the form of nanofibers; and (b) first freezing and drying the cast gel to form a membrane, sponge or foam.

In the method for preparing the hemostatic composition of the present invention, after step (b), (c) treating the membrane, sponge or foam obtained in step (b) with a gelation aid; and (d) secondly freezing and drying the membrane, sponge or foam of step (c).

When preparing a hemostatic dressing using the composition containing the cellulose in the form of nanofibers of the present invention, there is an advantage that a dressing having excellent hemostatic effect can be obtained even if only the primary freeze-drying is performed.

In this regard, freeze-drying is a method of freezing a sample at -80 ° C and then drying it through sublimation. It varies depending on the amount of sample, but basically it is a process that requires around 3 days for drying and 5 days or more for mass production. .

However, in the case of the hemostatic composition material containing cellulose in the form of nanofibers of the present invention, unlike the conventional material prepared by freeze-drying twice, it shows very excellent hemostatic efficacy with only one freeze-drying, thereby reducing more than half the period during manufacture It simplifies the manufacturing process and has the advantage of excellent productivity.

Accordingly, the hemostatic composition of the present invention has technical significance in that it can be put to practical use and commercialized by solving the problems of conventional dressings.

The novel hemostatic composition according to the present invention is well absorbed from the affected area, has excellent adhesiveness, does not cause an allergic reaction, and has excellent mechanical properties, water absorption, and formability.

In addition, the hemostatic dressing having an excellent hemostatic effect of the present invention has the advantage of excellent production efficiency as compared to conventional dressings that are manufactured in a simple process.

1 is a view showing a manufacturing process of cellulose in the form of nanofibers (Cellulose Nanofiber, CNF).
Figure 2 is a TEM image showing the result of confirming that the prepared cellulose nanofibers have a uniform diameter between 3 and 10 nm as a result of analysis.
Figure 3 is an analysis result confirming that it has a high surface modification rate of 1.5 ~ 2.2 mmol / g cellulose by analyzing carboxylate contents using an electric conductivity titration method.
Figure 4 is a view showing the process up to the first freeze-drying treatment of the process of manufacturing a foam using the nanofiber-type cellulose (Cellulose Nanofiber) of the present invention.
FIG. 5 is a view showing a process of deep freeze and freeze drying once more after crosslinking by supporting the foam, which has proceeded to the first freeze-drying treatment in FIG. 4, in a CaCl ₂ solution by count ion.
Figure 6 shows the results of confirming the wet absorption and strength maintenance after primary freeze-drying and secondary freeze-drying. <When only the first freeze-drying was performed (left), when the second freeze-drying was performed after crosslinking (right)>
Figure 7 is a view showing the process up to the first freeze-drying treatment of the manufacturing process of the cellulose nanofiber foam containing gallic acid. <Without gallic acid (left), with gallic acid (right)>
FIG. 8 is a view showing the results of performing the second freeze-drying after crosslinking the foam that has progressed to the first freeze-drying treatment of FIG. 7. <Surface irregularities including gallic acid during secondary lyophilization after crosslinking>
Figure 9 shows the results of confirming the foam retention form in a wet state after the first freeze-drying treatment and the second freeze-drying treatment of the cellulose nanofiber foam containing sodium alginate. < Wet state of primary freeze-dried foam (left), Wet state of secondary freeze-dried foam after crosslinking (right) >
Figure 10 shows the results of confirming the absorbance compared to the precipitate and the control group for each sample after the BCI test was performed.
11 is a view showing a composition for hemostasis in the form of a membrane prepared using cellulose (CNF) in the form of nanofibers according to the present invention.
12 is a view showing a composition for hemostasis in the form of a sponge prepared using nanofibrous cellulose (CNF) according to the present invention.
13 is a diagram showing the results of the BCI test according to the number of lyophilization in the manufacture of cellulose (CNF) in the form of nanofibers according to the present invention in photographs.
14 is a graph showing the BCI test results according to the number of lyophilization in the manufacture of nanofibrous cellulose (CNF) according to the present invention.
15 is a photograph showing the result of confirming the dissolution characteristics of sodium alginate (SA) in distilled water.
Figure 16 is a view showing the process up to the first freeze-drying treatment of the manufacturing process of cellulose nanofiber foam, cellulose nanofiber foam and cellulose nanocrystal (CNC) containing sodium alginate according to the present invention.
17 and 18 are pictures showing the BCI test results of the cellulose nanofiber foam, the cellulose nanofiber foam containing sodium alginate, and the cellulose nanocrystal (CNC) according to the present invention.
19 is a graph showing the BCI test results of a cellulose nanofiber foam, a cellulose nanofiber foam containing sodium alginate, and a cellulose nanocrystal (CNC) according to the present invention.
20 is a view showing the form according to the process when manufacturing a cellulose nanofiber foam, a cellulose nanofiber foam containing sodium alginate, a CNC foam, and a CNC foam containing sodium alginate according to the present invention.
21 is a view showing the shape of the CNC foam during washing.
22 is a view showing the results of confirming the strength according to the wet state during washing of the cellulose nanofiber foam according to the present invention, the cellulose nanofiber foam containing sodium alginate, the CNC foam, and the CNC foam containing sodium alginate.
23 is a view showing gauze supported with cellulose nanofiber foam hydrogel, gauze supported with chitosan, and untreated gauze according to the present invention.
24 is a diagram showing the results of BCI tests of gauze loaded with cellulose nanofiber foam hydrogel, gauze loaded with chitosan, and untreated gauze according to the present invention.
25 is a graph showing the BCI test results of gauze loaded with cellulose nanofiber foam hydrogel, gauze loaded with chitosan, and untreated gauze according to the present invention.

The terms used in the present invention have been selected from general terms that are currently widely used as much as possible, but in certain cases, there are terms arbitrarily selected by the applicant. Therefore, its meaning should be understood.

Hereinafter, the technical configuration of the present invention will be described in detail with reference to the accompanying drawings and preferred embodiments.

<Example 1> Preparation of Cellulose Nanofiber (CNF) and Analysis of Nanofiber

Cellulose nanofibers modified by TEMPO were prepared using high-purity food grade cellulose powder as a base material. This manufacturing process is shown in Figure 1.

Cellulose powder was subjected to TEMPO oxidizing, followed by washing and grinding to prepare Cellulose Nanofiber hydrogel.

The prepared cellulose nanofibers were analyzed by TEM (Transmission Electron Microscope), and the results are shown in FIG. 2 . As can be seen in Figure 2, nanofibers having a uniform diameter between 3 and 10 nm were confirmed.

In addition, its surface modification rate was confirmed by analyzing the carboxylate contents using the electric conductivity titration method. The results are shown in Figure 3.

As can be seen in Figure 3, the cellulose nanofibers prepared according to the present invention showed a high surface modification rate of 1.5 ~ 2.2 mmol / g cellulose.

<Example 2> Preparation of Cellulose Nanofiber Foam for hemostatic dressing

A foam was prepared using the nanofiber-type cellulose (Cellulose Nanofiber) prepared in Example 1.

Specifically, after casting a certain amount of cellulose nanofiber gel in the form of nanofibers (casting 100mL of cellulose nanofiber gel in a frame with a size of 12.5 cm x 12.5 cm), deep freeze -> Freeze drying and then the first freeze-drying A foam form was obtained after the treatment was completed, and the process thereof is shown in FIG. 4 .

In order to provide more strength in a wet state to the foam form after the first freeze-drying treatment prepared above, it was supported in CaCl ₂ solution by count ion, crosslinked, and deep freeze and freeze dry treatment were performed once more, and the process is shown in Figure 5.

In this preparation, the concentration of cellulose nanofibers should preferably be 1 wt% or more (dry weight of cellulose nanofibers 1 g or more) to obtain a form of foam that does not split after freeze-drying.

<Example 3> Confirmation of wet and wet strength of Cellulose Nanofiber Foam for hemostatic dressing

A water absorption test was conducted on the prepared foams subjected to the first freeze-drying treatment and the foams subjected to the second freeze-drying treatment, and the results are shown in FIG. 6 .

As can be seen in FIG. 6, it was confirmed that the foam absorbed water at least 6 times its own weight, and when freeze-dried after crosslinking, it had excellent strength enough to be lifted even in a wet state. It can be seen that there was.

< Example 4> Galsani included For hemostatic dressing Cellulose Nanofiber Manufacture of Foam

A foam was prepared using the same method as in Example 2 above using a mixture of gallic acid and cellulose nanofibers.

The results are shown in Figures 7 and 8.

As can be seen in Figure 7, it was confirmed that a very uniform white surface was formed on the surface after the primary freeze-drying. In addition, as can be seen in FIG. 8, unevenness, which appears to precipitate gallic acid on the surface in the secondary freeze-drying after crosslinking, was confirmed.

That is, the strength of the secondary freeze-dried foam with crosslinking was slightly lower than that of the foam prepared using only Cellulose Nanofibers, but it was confirmed that the strength was stronger in the case of crosslinking.

<Example 5> Preparation of Cellulose Nanofiber Foam for Hemostatic Dressing Containing Sodium Alginate

A foam was prepared in the same manner as in Example 2 using a mixture of sodium alginate and cellulose nanofibers. Specifically, the ratio of cellulose nanofibers was prepared in four types of 0, 10, 30, and 50%, and it was confirmed that the strength increased as the amount of cellulose nanofibers increased.

In addition, the wet state after the first and second freeze drying was compared and the results are shown in FIG.

As can be seen in FIG. 9, it was confirmed that the foam obtained by the primary freeze-drying maintained its shape in a wet state and had increased strength compared to the foam obtained by the secondary freeze-drying.

<Example 6> BCI test progress

Including the sample of the present invention, 1) 1 wt% CNF (Cellulose Nanofiber Foam) gel, 2) 1 wt% CNF + 1 wt% Gallic acid, 3) 1 wt% ChitinNF, 4) 1 wt% Chitosan (1000 MW) and 5) prepared by preparing 1 wt% Gallic acid. To perform the BCI test, it was prepared by adding 1M CaCl ₂ to ACD (anticoagulant)-added blood collected from rabbits (anticoagulant inactivation in blood). (Blood: ACD: 1 M CaCl ₂ = 0.270 ml: 0.030 ml: 0.024 ml). Then, 100 μl of blood prepared in step (1) was treated on the sample in the tube containing each sample, reacted at room temperature, and 50 ml of tertiary distilled water was administered to the reacted sample.

Next, after reacting at room temperature for 30 minutes, a 200 μl sample per well was placed in a 96-well transparent plate, and the absorbance at a wavelength of 540 nm was measured.

The results are shown in FIG. 10 .

In the case of the BCI test, a sample is put in blood and the absorbance of the supernatant is measured except for the coagulated and precipitated portion. The lower the value, the greater the precipitated amount, and therefore, it can be judged that a lot of blood coagulation has occurred. As can be seen in Figure 10, it was confirmed that the hemostatic effect of the CNF single sample was significantly greater.

<Example 7> Preparation of Cellulose Nanofiber Membrane for Hemostatic Dressing

Similar to the method of Example 2, a membrane was prepared using Cellulose Nanofiber, and it is shown in FIG. 11.

The membrane shown in FIG. 11 has a thinner shape than Form, so that it can be used on the affected area after being attached to a sheet or the like.

<Example 8> Preparation of Cellulose Nanofiber Sponge for Hemostatic Dressing

Similar to the method of Example 2, a sponge was prepared using Cellulose Nanofibers, and this is shown in FIG. 12.

In the case of this type of sponge, it is advantageous to apply to affected areas with a lot of exudate because it can absorb at least 6 to 14 times the weight of water compared to the weight of the sponge. In addition, other properties may be improved while controlling the amount of water absorbed by mixing additional materials with the cellulose nanofibers.

For example, when a sponge is produced by mixing sodium alginate as a specific material, the volume shrinks when moisture is absorbed, and through this, the disadvantage of existing sponges/foams that expand when water is absorbed is solved.

From the above results, it was confirmed that the cellulose nanofiber foam according to the present invention exhibits an excellent hemostatic effect while exhibiting a high wet content and excellent strength maintenance.

<Example 9> Hemostatic efficacy according to the number of times of freeze-drying in the manufacture of Cellulose Nanofiber Foam for hemostatic dressing

In order to analyze the hemostatic efficacy according to the number of times of lyophilization in the manufacture of Cellulose Nanofiber Foam for hemostatic dressings, the above-prepared 1st freeze-dried foam (CNF 1st FD) and 2nd freeze-dried foam (CNF 2nd FD), the BCI test was conducted using real blood for the CNF film before freeze-drying treatment, and the results are shown in FIGS. 13 and 14.

As can be seen in FIGS. 13 and 14, the hemostatic effect of the foam (CNF primary FD) after the first freeze-drying treatment was superior to the foam (CNF secondary FD) after the secondary freeze-drying treatment was found to be superior .

Thus, the cellulose nanofiber foam according to the present invention has an effect of shortening the manufacturing time by having a remarkably excellent hemostatic effect with only one freeze-drying.

< Example 10> conventional CNC (cellulose nanocrystal ) Compared to foam containing For hemostatic dressing Excellence of Cellulose Nanofiber Foam

Conventional cellulose nanocrystal (CNC) has a low aspect ratio, so it is difficult to form a single matrix structure. Therefore, a matrix is formed by fixing the CNC by mixing sodium alginate.

On the other hand, the Cellulose Nanofiber Foam (CNF) according to the present invention has a high aspect ratio, so that hydrogen bonds between chains and fibers form a network structure to form a three-dimensional matrix structure, and it has a remarkable effect of maintaining a stable form even without crosslinking treatment. there is.

In other words, Cellulose Nanofiber Foam (CNF) according to the present invention can realize a single stable foam form without sodium alginate, which is conventionally used to form a matrix, and can have high hemostatic efficacy.

This is because the reduction of reactive sites having hemostatic effect by reacting with functional groups on the surface of cellulose during crosslinking is reduced, so that very good hemostatic effect can be exhibited with only one lyophilization without crosslinking treatment.

In addition, sodium alginate (SA) used to form a matrix structure of conventional CNC (cellulose nanocrystal) has a melting point of 300 ° C. In order to dissolve it in distilled water, it must be dissolved while stirring at a temperature of 100 ° C for a long time, requiring a lot of energy and time. This is required, and in particular, at a concentration of 2w% or more, there is a problem in that it is not dissolved even when stirred at 100 ° C for a long time.

In addition, when sodium alginate comes in contact with distilled water, a slippery film is formed on the surface, but there is a problem that it is not well dissolved inside the film.

This can be confirmed through FIG. 15 showing the result of stirring sodium alginate at a temperature of 100 ° C. for 2 hours or more.

<Example 11> Comparison between conventional CNC foam and Cellulose Nanofiber Foam for hemostatic dressing of the present invention

Cellulose Nanofiber Foam for hemostatic dressing according to the present invention, 1) 2 wt% CNF 100 ml, 2) 2 wt% CNF + 2 wt% sodium alginate (hereinafter referred to as SA) 100 ml, 3) 2 wt% CNC 100 ml, respectively After casting on a square plate, it was freeze-dried. Thereafter, each sample was cut into 2 * 2 cm without separate cross-linking treatment, and then a BCI test was performed, and the results are shown in FIGS. 16 to 19.

As can be seen in FIG. 16, 2 wt% CNC was found to be released without maintaining its shape when in contact with a liquid. Since this affects the reduction of hemostatic efficacy, an additional material such as sodium alginate may be used to maintain the shape, but there are problems as described in Example 10 above.

On the other hand, 2 wt% CNF according to the present invention was found to stably maintain the structure without deformation of the shape even when in contact with liquid and exhibit excellent hemostatic efficacy.

Therefore, Cellulose Nanofiber Foam for hemostatic dressing according to the present invention has good hemostatic effect even with only Cellulose Nanofiber Foam alone and maintains a stable form even when in contact with blood, so it is suitable as a material for hemostatic dressing.

<Example 12> Comparison of TEMPO-CNC foam and TEMPO-Cellulose Nanofiber foam of the present invention

100 mml each of 1) 2 wt% CNF, 2) 2 wt% CNF + 2 wt% sodium alginate (SA), 3) 2 wt% CNC, 4) TEMPO-CNC + 2 wt% SA prepared according to the present invention After preparing each, casting on a square plate, first freeze-drying, crosslinking and washing, structural stability was analyzed, and a BCI test was performed. The results are shown in FIGS. 20 to 22.

As can be seen in Figure 20, the sample containing CNF of the present invention was found to maintain a stable shape compared to the sample containing CNC. In particular, in the case of the CNC alone sample, the structure was released while in contact with the liquid, and the shape was not maintained and decomposed during washing three times (FIG. 21).

In addition, in order to confirm the strength in the wet state during washing, a test of lifting the wet foam during washing was performed. As can be seen in FIG. 22, in the case of the sample containing the CNF of the present invention, the entire foam was lifted Maintained enough strength to lift. However, in the case of samples containing CNC, the strength was reduced to such an extent that it was difficult to lift.

In addition, as a result of conducting a BCI test with the foam obtained by cross-linking and washing the sample after the first freeze-drying (secondary freeze-drying), the sample containing CNC showed a phenomenon in which it was released while in contact with the liquid, showing hemostatic efficacy. decreased, and in the case of CNF, hemostatic efficacy was not improved even when SA was added.

In addition, in the case of TEMPO CNC / SA foam, the hemostatic efficacy was partially improved compared to CNC, but it showed lower hemostatic efficacy than CNF, so the CNF of the present invention has a simpler manufacturing process than conventional CNC, as well as hemostatic efficacy There is also a remarkably good effect in .

<Example 13> Comparative analysis of hemostatic effect of TEMPO-Cellulose Nanofiber foam and chitosan of the present invention

Gauze supported on 2 wt% CNF hydrogel prepared according to the present invention, 2) gauze supported on 2 wt% Chitosan solution and untreated sterile medical gauze as a control group were lyophilized under the same conditions to perform the BCI test. The results are shown in Figures 23 to 25.

As can be seen in FIGS. 24 and 25, the gauze (gauze/Chitosan) supported in the 2 wt% Chitosan solution showed almost similar values to the control group (only gauze was used), but the values supported in the 2 wt% CNF hydrogel Gauze (gauze/CNF) showed more than twice the hemostatic efficacy compared to the control group (gauze only).

Compared to Chitosan, which is known to have good hemostatic efficacy, the CNF according to the present invention has a much greater hemostatic effect even with the addition of a small amount.

Claims (19)

Including cellulose in the form of nanofibers (Cellulose Nanofiber),
The cellulose has an aspect ratio of 1/100 to 1/600, is surface modified by TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical), and has a surface modification rate of 1.5 to 2.0 mmol/g. Cellulose, a composition for hemostasis. delete delete The hemostatic composition according to claim 1, wherein the surface-modified cellulose has a carboxyl group substituted at carbon 6 of the cellulose. delete The hemostatic composition according to claim 1, wherein the cellulose in the form of nanofibers has a diameter of 1 to 10 nm. The hemostatic composition according to claim 1, wherein the cellulose in the form of nanofibers has a length of 500 nm to 10 μm. According to claim 1, wherein the nanofibrous cellulose is a mixture of crystalline and amorphous, hemostatic composition. [Claim 9] The composition for hemostasis according to claim 8, wherein the crystallinity of the cellulose in the form of nanofibers is 40 to 70%. According to claim 1, wherein the composition for hemostasis further comprises a compound capable of generating sodium ions, potassium ions, magnesium ions, or calcium ions as a gelling aid, composition for hemostasis. 11. The method of claim 10, wherein the gelling aid is sodium chloride (NaCl), potassium chloride (KCl), magnesium chloride (MgCl ₂ ), calcium chloride (CaCl ₂ ), sodium hydroxide (NaOH), potassium hydroxide (KOH) and potassium carbonate ( K ₂ CO ₃ ) One or more compositions for hemostasis selected from the group consisting of. According to claim 1, wherein the composition for hemostatic composition for hemostasis further comprises a component enhancing the hemostatic effect. According to claim 1, wherein the composition for hemostatic composition for hemostasis further comprises a gel-reinforcing material. The hemostatic composition according to claim 13, wherein the gel-reinforcing material is sodium alginate or gallic acid. According to claim 1, wherein the composition for hemostasis is a hydrogel formulation, the composition for hemostasis contained in 0.1 wt% to 10 wt% in the composition. The composition for hemostasis according to claim 1, wherein the composition for hemostasis is a membrane, foam or sponge formulation, and is contained in an amount of 10 wt% or more in the composition. A dressing comprising the composition for hemostasis according to any one of claims 1, 6 and 16. (a) casting a gel comprising cellulose in the form of nanofibers; and
(b) forming a membrane, sponge or foam by first freezing and drying the cast gel; the method for preparing the hemostatic composition of claim 1, comprising: The method of claim 18, after step (b), (c) treating the membrane, sponge or foam obtained in step (b) with a gelling aid; and
(d) further comprising the step of secondly freezing and drying the membrane, sponge or foam of step (c), the method for producing a hemostatic composition.

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