KR102350122B1 - Absorbable hemostat pad having chitosan and, manufacturing methods for the same - Google Patents

Abstract

The absorbent hemostatic pad according to the present invention, when applied to a surgical site, absorbs blood and secretions at a fast rate and expands only 1.5 times, has excellent tissue adhesion, gels at a fast rate, and is naturally decomposed and removed in the human body. have

Description

Absorbable hemostat pad having chitosan as a main component, and manufacturing method thereof

The present invention relates to an absorbent hemostatic pad, and more specifically, when applied to a bleeding site, it effectively absorbs blood and secretions at a fast rate and expands only 1.3 to 1.7 times, so it is safe, has excellent tissue adhesion, and gels at a fast rate. , to an absorbent hemostatic pad that is naturally decomposed and removed in the human body. The present invention also relates to a method for making such an absorbent hemostatic pad.

In general, bleeding occurs when blood vessels are injured by physical trauma, including surgical operations. Depending on the degree of damage, bleeding can cause blood loss to a degree that can affect the normal body functions of the individual. It can also cause damage to the tissue due to increased pressure. If bleeding is left unattended, bleeding is stopped by a physiological process characterized by a complex chain reaction between blood vessels, platelets and plasma factors. This process is called physiological hemostasis. In the case of mild superficial bleeding, this physiological hemostasis is sufficient to stop the bleeding.

However, if the bleeding results from more serious injuries, especially if these injuries involve large arteries or result in blood outflow from larger mucosal surfaces, or if they occur in cavities without outlets, surgical and/or internal medicine Red hemostatic means are required. Surgical bleeding suppression can include ligation or suturing of ruptured blood vessels, filling with cotton balls in the case of cavities, application of heated instruments, caustics, or coagulation of the tissue surface to which the ruptured blood vessels are exposed by heated air. have.

Bioabsorbable hemostatic sponges made of appropriately sized blocks, plates, and films may be applied to the wound to aid in surgical hemostasis.

These hemostatic sponges are used in surgeries of large abdominal organs (liver, spleen, or small intestine), lung surgery, neurosurgery to prevent pressure-induced damage to the brain or nerve tissue, and other procedures that are difficult to control and frequently occur. It is useful to enhance the suppression of bleeding in some cases of orthopedic surgery with extensive bleeding, vascular surgery to prevent seeping bleeding from sutures, oral or dental surgery such as tooth extraction, or other injuries.

The existing gelatin sponge absorbs about 45 times its own weight when attached to the bleeding site, and thus the sponge volume inevitably increases a lot. However, if the sponge is not used according to the regulations, it may cause side effects such as damage to nerves due to the swelling.

Accordingly, there is a demand for a hemostatic sponge that expands to a smaller range than a conventional hemostatic sponge while maintaining a sufficient hemostatic effect.

On the other hand, chitosan is a biocompatible material having a hemostatic effect, and is used as a hemostatic agent during surgery. US 4,394,373 discloses a configuration for coagulating blood by using chitosan in liquid or powder form, US 4,452,785 discloses a method of therapeutically occluding blood vessels by directly injecting chitosan into blood vessels, US 4,532,134 discloses a configuration for promoting hemostasis, fibrous tissue formation, and tissue regeneration by contacting a tissue wound with a chitosan solution or water-soluble chitosan.

However, when the hemostatic agent is applied to the surgical site, it should be able to effectively absorb blood and secretions at a fast rate, have excellent tissue adhesion, gel at a fast rate, and be naturally decomposed and removed in the human body. There are no hemostatic agents available.

The present invention has been proposed to solve the above problems, and it is an object of the present invention to provide an absorbent hemostatic pad that expands only 1.3 to 1.7 times while effectively absorbing blood and secretions at a fast rate when applied to a bleeding site, and a method for manufacturing the same. .

Another object of the present invention is to provide an absorbent hemostatic pad that has excellent tissue adhesion, gels at a fast rate, and is naturally decomposed and removed in the human body, and a method for manufacturing the same.

In order to solve the above problems, the method for manufacturing an absorbent hemostatic pad according to the present invention comprises (a) 0.5 to 1.5 parts by weight of chitosan per 100 parts by weight of solvent and 0.2 to 0.8 parts by weight of an organic acid having 1 to 10 carbon atoms by mixing and stirring the gel ( gel) state; (b) removing the gas contained in the mixture by stirring the mixture; (c) freezing the mixture in the gel state at -8°C to -3°C for 7 hours to 13 hours; (d) freeze-drying the frozen mixture; and, (e) heating the freeze-dried porous pad (mixture) to heat treatment.

The weight of the organic acid in step (a) is 30% to 60% of the weight of chitosan, and in step (d), the frozen mixture of step (c) is heated to 7° C. to 13° C. over 12 hours to 16 hours. . At this time, when the freeze-drying starts, the inside of the chamber is at atmospheric pressure, and in the last stage of the freeze-drying, the inside of the chamber is approximately 18-20 mTorr.

And, the step (e) is heated at 110 ℃ to 130 ℃ for 3 minutes to 10 minutes. When the heating time is less than 3 minutes, the water absorption power is lowered, and when the heating time exceeds 10 minutes, the gelation rate becomes slow, which is not preferable.

The absorbent hemostatic pad manufactured through the above process absorbs blood or exudate leaking from the blood vessel or incision at the surgical site, forms a hemostatic barrier, and turns into a gel within 5 minutes after being applied to the surgical site, and blood or exudate It expands by 1.3 to 1.7 times by absorption.

The freeze-drying of step (d) may be performed while raising the temperature in a stepwise manner. Specifically, the step (d) includes: (d1) maintaining the temperature of the mixture constant for a first time (Δm1); (d2) after step (d1), increasing the temperature of the mixture by ΔT for a second time period (Δm2); and, (d3) after step (d2), repeating steps (d1) and (d2) until the temperature of the mixture reaches 7°C to 13°C. When the freeze-drying starts, the pressure inside the chamber is atmospheric pressure, and as the moisture evaporates, the pressure continues to decrease to maintain 18-20 mTorr during final drying (the last stage of freeze-drying).

The solvent is preferably distilled water, ultrapure water, or deionized water, and the organic acid is glycolic acid in an amount of 0.5 parts by weight and chitosan is preferably 1 part by weight. Compared to the conventional sponge using acetic acid, in the present invention, glycolic acid can be used to prevent a peculiar unpleasant odor.

The absorbent hemostatic pad according to the present invention is ^{a sponge-type hemostatic pad having a density of 0.013 g/cm 3} to 0.02 g/cm ³ after the heat treatment and including a freeze-dried and heat-treated structure. And, it has a composition ratio of 0.5 to 1.5 parts by weight of an organic acid having 1 to 10 carbon atoms and 0.05 to 0.5 parts by weight of water per 100 parts by weight of chitosan.

The absorbent hemostatic pad according to the present invention has the following effects.

First, when applied to the bleeding site, it expands only 1.3 to 1.7 times while effectively absorbing blood and secretions at a fast rate.

Second, it has excellent tissue adhesion, gels at a fast rate, and is naturally decomposed and removed in the human body.

1 is a photograph showing an absorbent hemostatic pad according to a preferred embodiment of the present invention.
Figure 2 is a flow chart showing a method for making the absorbent hemostatic pad of Figure 1;
3 is a graph showing the relationship between temperature and time during freeze drying in the manufacturing process of FIG. 2 .

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings. Prior to this, the terms or words used in the present specification and claims should not be construed as being limited to conventional or dictionary meanings, and the inventor should properly understand the concept of the term in order to best describe his invention. Based on the principle that it can be defined, it should be interpreted as meaning and concept consistent with the technical idea of the present invention. Accordingly, the embodiments described in this specification and the configurations shown in the drawings are merely embodiments of the present invention and do not represent all the technical spirit of the present invention, so various equivalents that can be substituted for them at the time of the present application It should be understood that there may be variations and examples.

1 is a photograph showing an absorbent hemostatic pad according to a preferred embodiment of the present invention, and FIG. 2 is a flow chart showing a method for manufacturing the absorbent hemostatic pad.

As shown in the figure, the method for manufacturing the absorbent hemostatic pad includes the steps of preparing a mixture by mixing chitosan with an organic acid having 1 to 10 carbon atoms and a solvent (S1), removing the bubbles contained in the mixture (S2), Stabilizing the mixture (S3), freeze-drying the mixture (S4), heat-treating the freeze-dried porous pad (mixture) (S5), and disinfecting and vacuum drying (S6). Each of the above steps will be described below.

First, an organic acid having 1 to 10 carbon atoms is added to the solvent.

The solvent may be a polar solvent, and in some embodiments, the solvent may be an aqueous solvent. For example, the solvent is preferably deionized water, distilled water, ultrapure water, etc., but is not necessarily limited thereto. In some embodiments, the solvent may be a polar organic solvent having 1 to 10 carbon atoms. In some embodiments, the solvent may be an alcohol-based solvent having 1 to 10 carbon atoms.

The organic acid having 1 to 10 carbon atoms may be an organic acid including a carboxylic group (-COOH). In some embodiments, the organic acid having 1 to 10 carbon atoms may be an organic acid including both a carboxy group and a hydroxyl group (-OH). For example, the organic acid having 1 to 10 carbon atoms may be an organic acid having a general formula of HO-R-COOH or HOOC-R-COOH. Here, R may be a straight-chain or branched alkylene group having 1 to 8 carbon atoms. For example, the organic acid having 1 to 10 carbon atoms is glycolic acid, lactic acid, acetic acid, lactic acid, formic acid, acrylic acid, propinic acid, succinic acid, oxalic acid, succinic acid, ascorbic acid, gluconic acid, tartaric acid, maleic acid, citric acid, and glutamic acid It may be at least one selected from the group consisting of. However, the present invention is not limited thereto.

On the other hand, the organic acid is added to improve the solubility of chitosan in a solvent. In particular, when glycolic acid is used as the organic acid, there is an advantage that the final product (hemostatic pad) does not have an odor compared to other acids.

Then, chitosan is added and stirred to make a mixture in a gel state (S1).

Specifically, 0.5 to 1.5 parts by weight of chitosan per 100 parts by weight of the solvent and 0.2 to 0.8 parts by weight of an organic acid having 1 to 10 carbon atoms are mixed and stirred to prepare a gel mixture. The weight of the organic acid in the mixture is 30% to 60% of the weight of the chitosan, preferably the weight of the organic acid is 50% of the weight of the chitosan. More preferably, the mixture has 1 part by weight of chitosan and 0.5 parts by weight of glycolic acid per 100 parts by weight of distilled water.

If the composition ratio of the mixture is less than the lower limit or greater than the upper limit, it is difficult to prepare a hemostatic agent having desired physical properties (tissue adhesion, hemostatic effect, etc.).

The stirring is performed, for example, at room temperature and at 850 to 1000 R.P.M. for 1 hour. And, the ash content contained in chitosan, an organic acid having 1 to 10 carbon atoms, etc. is preferably less than 1%.

When the preparation of the mixture is completed, the mixture is placed in a centrifuge and rotated or stirred to remove bubbles contained in the mixture (S2). This process may also take place in a vacuum. This process is to prevent the inclusion of unnecessary air bubbles inside the product (hemostatic pad).

Then, the mixture is placed in a tray of a predetermined size and then frozen (S3, pre-freezing process). Specifically, the mixture in the gel state is frozen at a temperature between -8°C and -3°C, preferably at -5°C, for 7 hours to 13 hours, preferably for 10 hours. The freezing is performed under atmospheric pressure.

The freezing process (S3) allows the chitosan particles to be uniformly distributed in the mixture. If the chitosan particles are not uniformly distributed in the mixture, a layer is formed on the product (hemostatic pad), which is undesirable.

When the freezing temperature is higher than -3 ° C, the chitosan particles are distributed a lot in the upper part of the mixture and relatively small in the lower part, and it takes too much time to freeze and the pore size is too large, so it is difficult to maintain the pad shape. not.

In addition, when the freezing temperature is lower than -8°C, the pore size becomes small and the water absorption power is significantly lowered, which is not preferable.

In contrast, when frozen at a temperature between -8°C and -3°C, the pore size is appropriate, moisture absorption is high, and the gelation rate is increased, which is preferable.

And, if the freezing time is less than 7 hours, the time for uniform diffusion of chitosan particles in the mixture is insufficient, and the freezing state may be poor. It is undesirable because it is insufficient or absent.

When the freezing process (S3) is completed, the mixture is freeze-dried (S4). Freeze drying is a method of freezing materials and then sublimating them to vapor in a gaseous state without going through a liquid state in a vacuum device and drying them. As it is removed, the dried product has the form of a light sponge. As used herein, 'sponge' refers to a porous structure and has a network shape, and has a structure with an inner surface much wider than its outer surface, that is, it contains a hollow space inside the network structure and contains a liquid several times its own weight. It has the ability to absorb.

The freeze-drying is made while increasing the temperature of the frozen mixture.

Specifically, in the freeze-drying step of the present invention, the temperature of the mixture subjected to the freezing step (S3) is raised stepwise for 12 hours to 16 hours, preferably 14 hours, so that it is 7°C to 13°C, preferably 10°C. The temperature rise may be in a stepwise fashion, as will be explained below.

According to the present applicant, through long research and experience, if the temperature of the hemostatic agent is gradually increased while freeze-drying, the hemostatic agent has different physical properties, that is, when blood is absorbed, it becomes a gel in a short time (within about 5 minutes). It was found that it has the physical properties of being strongly adhered to the tissue and continuously changing into a gel from the bottom part in contact with blood to a highly viscous gel.

3 shows an example of increasing the temperature of the mixture in the freeze-drying process. As shown in the figure, the temperature of the mixture (-5°C) that has undergone the freezing step (S3) is kept constant for the first time (Δm1), and then the temperature is increased by ΔT°C for the second time (Δm2). Raise the temperature to 10° C. by repeating the raising for approximately 14 hours. Table 1 below shows these temperature rises.

One The frozen mixture was kept at -5°C for 1.4 hours (Δm1). ※ The pressure inside the freeze-drying chamber is atmospheric pressure at the start of freeze-drying, and as the moisture evaporates, the pressure continues to decrease, maintaining 18-20 mTorr during final drying. 2 Raise to -2.5°C (ΔT°C) for 0.6 hours (Δm2) 3 -2.5°C was maintained for 1.4 hours (Δm1), and then raised to 0°C (ΔT°C) over 0.6 hours (Δm2) 4 The stepwise temperature rise as above was carried out over a total of 14 hours to 10℃.

Meanwhile, the first time (Δm1) and the second time period (Δm2) are preferably 60 minutes to 120 minutes, and ΔT is preferably 2°C to 5°C. In addition, the first and second times Δm1 (Δm2) and ΔT may not be the same in each step and may be variable as long as these ranges are satisfied. That is, the first time Δm1 may not be the same for each step and may be different from each other, the second time Δm2 may also be different for each step, and ΔT may also be different for each step.

This stepwise temperature rise has the effect of making the physical properties of the hemostatic agent more uniform because the mixture has time to be stabilized for the first time (Δm1).

When the freeze-drying process (S4) is completed, the porous pad (mixture) is heated (heat-treated) in an oven (S5). The heat treated pad is 0.013 g/cm ³ It has a density of ~ 0.02 g/cm ^{3 .}

On the other hand, the present applicant, through many years of research and experience, found that the heat treatment temperature and time are related to the gelation rate, water absorption capacity, and expansion rate of the hemostatic pad. It has been found that it is most desirable to heat the lyophilized mixture at 110° C. to 130° C. for 3 minutes to 10 minutes. The hemostatic pad that has undergone this heat treatment process absorbs blood well, gels within 5 minutes when applied to the surgical site, and has an expansion rate of 1.3 to 1.7 times. On the other hand, when the heat treatment time exceeds 10 minutes, the gelation rate is slowed, and when the heat treatment time is less than 3 minutes, there is a problem in that the water absorption power is lowered.

When the heat treatment process (S5) is completed, the hemostatic pad is sterilized and vacuum dried (S6). Specifically, after neutralization and sterilization by immersing the hemostatic pad in 70% ethanol, vacuum drying is performed at a temperature of 80° C. to remove the ethanol.

When the process (S6) is completed, the pad is packaged.

Thus prepared hemostat pad will have a density of chitosan, 100 parts by weight of an organic acid having 1 to 10 carbon atoms per 0.5 to 1.5 part by weight, have a ratio of 0.05 to 0.5 parts by weight of water, 0.013g / cm ³ to 0.02g / cm ³ .

If the composition ratio of the hemostatic pad is lower than the lower limit or higher than the upper limit, it is not preferable in terms of hemostatic effect, adhesion to the surgical site, time to change into a gel, expansion rate, and the like.

And, a more preferable effect occurs when the chitosan content is 98.5 wt% to 99.5 wt% and the organic acid is glycolic acid (1 wt%).

On the other hand, when the hemostatic pad according to the present invention is applied to a bleeding site (surgical site), it continuously absorbs blood or exudates leaking from blood vessels or incisions, and forms a hemostatic barrier, and the entire pad turns into a gel. In addition, the adhesive strength is excellent due to the attraction between the ions between the positively charged chitosan and the negatively charged red blood cells. When there is a lot of bleeding, the gelation rate is increased and the film formation rate is also accelerated. In contrast, when the amount of blood or exudate is small, a portion remaining in the form of foam exists around the pad, but it gradually gels within 5 minutes to form a hemostatic film. If there is a part remaining as foam even after a certain period of time, it is changed into a gel when moisture is supplied using saline or the like.

There is no need to separately remove the gel pad as it is safely decomposed and absorbed through hydrolysis in the human body.

Hereinafter, examples will be described in detail to help the understanding of the present invention. However, the embodiments according to the present invention may be modified in various other forms, and the scope of the present invention should not be construed as being limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art.

Example 1

(Example 1-1)

A mixture of 1.0 parts by weight of chitosan and 0.5 parts by weight of glycolic acid per 100 parts by weight of distilled water is mixed and stirred to form a gel mixture, air bubbles contained in the mixture are removed, and then frozen at -5°C for 10 hours, then frozen Drying was carried out through a stepwise temperature change process and pressure change process as shown in FIGS. 3 and 1, and then the freeze-dried mixture was heat-treated at a temperature of 120° C. for about 4 minutes to prepare a porous sponge of ^{0.017 g/cm 3} .

(Comparative Example 1-1)

A hemostatic pad was prepared in the same manner as in Example 1-1, except that 0.3 parts by weight of chitosan and 0.15 parts by weight of glycolic acid were mixed per 100 parts by weight of distilled water.

(Comparative Example 1-2)

The hemostatic agent of Comparative Example 1-2 is a commercially available gelatin sponge (Surgifoam ^® ).

The hemostatic test of the hemostatic pad was performed in the following way. Pigs were selected because they have a large amount of blood and the blood vessels of the spleen are well developed so that the hemostatic effect can be compared several times.

An incision was made in the midline of the pig's abdomen to expose the spleen, and an incision with a length of 1.0 cm and a depth of 2 mm was made in the spleen. Hemostasis time was measured by attaching the hemostatic pad of Examples 1-1 and Comparative Examples 1-1 and 1-2 and gauze moistened with saline (negative control) to each incision by hand for 2 minutes. The test was stopped if bleeding did not stop within 5 minutes and/or if the sponge was saturated without reducing bleeding. Table 2 below shows the hemostasis time.

pad Hemostasis time (min) note Example 1-1 4 After application to the incision, the pad gels and stops hemostasis within 4 minutes. Comparative Example 1-1 > 6 The test was stopped as the sponge was saturated and no reduction in bleeding was observed. Comparative Example 1-2 (Gelatin Sponge) > 7 The test was stopped as the sponge was saturated and no reduction in bleeding was observed. negative control > 12 Hemostasis takes more than 12 minutes

As shown in Table 2 above, when the composition ratio of the hemostatic pad was the same as that of Example 1-1, hemostasis was achieved within 5 minutes, but when the composition ratio was the same as that of Comparative Example 1-1, hemostasis was not well achieved.

On the other hand, when the content of chitosan is too high (when the content of chitosan exceeds 1.5 per 100 parts by weight of the solvent), the viscosity of the mixture increases, so that it is difficult to stir, thereby making it difficult to manufacture. Accordingly, the composition ratio of the hemostatic pad is 0.5 to 1.5 parts by weight of chitosan and 0.2 to 0.8 parts by weight of glycolic acid per 100 parts by weight of the solvent, and the weight of glycolic acid is preferably 30% to 60% of the weight of chitosan.

Example 2

(Example 2-1)

A hemostatic pad was prepared in the same manner as in Example 1-1.

(Comparative Example 2-1)

It was the same as in Example 1-1 except that the mixture was frozen at -10°C for 10 hours.

(Comparative Example 2-2)

It was the same as in Example 1-1 except that the mixture was frozen at -2°C for 10 hours.

(Comparative Example 2-3)

The hemostatic agent of Comparative Example 2-3 is a commercially available gelatin sponge (Surgifoam ^® ).

The hemostatic pad was tested in the following way.

The hemostatic pad of Example 2-1 and Comparative Examples 2-1 to 2-3 was cut into 4 cm (horizontal) × 6 cm (length) × 0.4 cm (thickness), respectively, and then completely wetted with physiological saline to measure the gelation time. .

Then, the hemostatic pad of Example 2-1 and Comparative Examples 2-1 to 2-3 was cut with a knife and the cross-section was observed under a microscope to measure the relative size of the pore size, and the chitosan particles were relatively uniformly distributed on the upper and lower portions of the cross-section. distribution was observed.

pad gel time
(minute) Relative size of pore size Uniformity of Chitosan Particle Distribution time to completely freeze Example 2-1 < 5 middle uniform 9-10 hours Comparative Example 2-1 ≒ 20 cow uniform 6-7 hours Comparative Example 2-2 < 5 big non-uniformity 34-37 hours Comparative Example 2-3 > 20 cow uniform -

As shown in Table 3, when the mixture was frozen at -5°C, compared to the case where the mixture was frozen at a low temperature (-10°C) (Comparative Example 2-1), the water absorption rate was large because the pore size was large. is fast, so the gelation rate is fast. And, it can be seen that the chitosan is uniformly distributed on the upper and lower parts of the pad.

On the other hand, as in Comparative Example 2-2, when the freezing of the mixture was made at -2°C, it takes too much time to freeze, the pore size is too large, making it difficult to maintain the shape of the pad, and the chitosan content in the upper and lower parts of the pad is This is not desirable because it makes a difference. Therefore, the freezing of the mixture is preferably made at -8 ℃ ~ -3 ℃.

Example 3

(Example 3-1)

A hemostatic pad was prepared in the same manner as in Example 1-1.

(Comparative Example 3-1)

It was the same as in Example 1-1 except that the frozen mixture was freeze-dried at a constant temperature of -5°C for 14 hours.

The gelation test of the hemostatic pad was performed as follows.

An incision was made on the midline of the pig's abdomen to expose the spleen, and an incision with a length of 1.0 cm and a depth of 2 mm was made in the spleen. The hemostatic pad of Example 3-1 and Comparative Example 3-1 was attached to each incision by hand pressing for 2 minutes to measure the hemostatic time and the gelation time. Table 4 below shows the test results.

pad Gelation time (min) Hemostasis time (min) Example 3-1 < 5 < 5 Comparative Example 3-1 > 20 -

As shown in Table 4, when the hemostatic pad of Example 3-1 is attached to the incision site, it is gelled from the bottom part by the blood and exudate discharged from the incision site and is strongly attached, and the upper part also begins to gradually change to a gel, compared to The hemostatic pad of Example 3-1 takes a lot of time to gel (approximately 20 minutes or more). This seems to be because the freeze-drying temperature was made at a constant temperature of -5 °C.

Example 4

(Example 4-1)

A hemostatic pad was prepared in the same manner as in Example 1-1.

(Comparative Example 4-1)

The freeze-dried mixture was heat-treated at a temperature of 120° C. for 2 minutes ^{to make a porous sponge of 0.017 g/cm 3 in} the same manner as in Example 1-1.

(Comparative Example 4-2)

The freeze-dried mixture was heat-treated at a temperature of 120° C. for 11 minutes to prepare ^{a porous sponge of 0.018 g/cm 3 in} the same manner as in Example 1-1.

The gelation test and water absorption test were performed using the hemostatic pad of Example 4-1 and Comparative Examples 4-1 and 4-2 as follows.

For the gelation test, the spleen was exposed by incision at the midline of the pig's abdomen, and an incision of 1.0 cm in length and 2 mm in depth was made in the spleen. The gelation time was measured by attaching it to the incision by hand pressing for 2 minutes.

In the water absorption test, 10 mg of each hemostatic pad was cut and completely wetted with physiological saline, and then the weight was measured. Table 5 below shows the test results.

pad Gelation time (min) Water absorption (g/g) Example 4-1 < 5 27.2 Comparative Example 4-1 < 5 15.4 Comparative Example 4-2 > 10 26.0

As shown in Table 5, the hemostatic pad of Example 4-1 had a gelation time of less than 5 minutes and a water absorption of 27.2 g/g, whereas the hemostatic pad of Comparative Example 4-1 had a small amount of water absorption. However, the hemostatic pad of Comparative Example 4-2 is not preferable because it takes 10 minutes or more to gel.

Accordingly, the heat treatment is preferably performed at 110° C. to 130° C. for 3 minutes to 10 minutes.

Δm1: first time Δm2: second time
ΔT: the temperature that rises during the second time period (Δm2)

Claims (7)

(a) mixing 0.5 to 1.5 parts by weight of chitosan and 0.2 to 0.8 parts by weight of an organic acid having 1 to 10 carbon atoms per 100 parts by weight of an aqueous solvent and stirring to make a gel mixture;
(b) removing the gas contained in the mixture by stirring the mixture;
(c) freezing the mixture in the gel state at -8°C to -3°C for 7 hours to 13 hours;
(d) freeze-drying the frozen mixture; and,
(e) heating the freeze-dried porous pad;
Step (e) is heated at 110 ° C. to 130 ° C. for 3 minutes to 10 minutes,
Absorbs blood or exudate leaking from blood vessels or incisions at the surgical site, forms a hemostatic barrier, turns into a gel within 5 minutes after being applied to the surgical site, and expands 1.3 to 1.7 times by absorption of blood or exudates ,
When the preparation is completed, 0.013 ^{g/cm 3} to 0.02 g/cm ³ A method for manufacturing an absorbent hemostatic pad, characterized in that it is a porous sponge having a freeze-dried structure and having a density of 0.013 g/cm 3 to 0.02 g/cm 3 . According to claim 1,
The method of manufacturing an absorbent hemostatic pad, characterized in that the weight of the organic acid in step (a) is 30% to 60% of the weight of chitosan. (a) mixing 0.5 to 1.5 parts by weight of chitosan and 0.2 to 0.8 parts by weight of an organic acid having 1 to 10 carbon atoms per 100 parts by weight of the solvent and stirring to prepare a mixture in a gel state;
(b) removing the gas contained in the mixture by stirring the mixture;
(c) freezing the mixture in the gel state at -8°C to -3°C for 7 hours to 13 hours;
(d) freeze-drying the frozen mixture; and,
(e) heating the freeze-dried porous pad;
Step (e) is heated at 110 ° C. to 130 ° C. for 3 minutes to 10 minutes,
Absorbs blood or exudate leaking from blood vessels or incisions at the surgical site, forms a hemostatic barrier, turns into a gel within 5 minutes after being applied to the surgical site, and expands 1.3 to 1.7 times by absorption of blood or exudates ,
The weight of the organic acid in step (a) is 30% to 60% of the weight of chitosan,
Step (d) is a method of manufacturing an absorbent hemostatic pad, characterized in that the temperature of the mixture frozen in step (c) is raised in a vacuum from 7°C to 13°C over 12 hours to 16 hours. 4. The method of claim 3,
The absorbent hemostatic pad is a method of manufacturing an absorbent hemostatic pad, characterized in that it is a porous sponge having a density ^{of 0.013 g/cm 3} to 0.02 g/cm ^{3 and a freeze-dried structure.} It is an absorbent hemostatic pad made by the manufacturing method of any one of claims 1 to 4,
A porous sponge having a density of 0.013 g/cm ³ to 0.02 g/cm ³ and comprising a freeze-dried structure,
It has a composition ratio of 0.5 to 1.5 parts by weight of an organic acid having 1 to 10 carbon atoms and 0.05 to 0.5 parts by weight of water per 100 parts by weight of chitosan,
Absorbs blood or exudate leaking from blood vessels or incisions at the surgical site and forms a hemostatic barrier.
Absorbable hemostatic pad, characterized in that it turns into a gel within 5 minutes after being applied to the surgical site, and expands 1.3 to 1.7 times by blood or exudate absorption. delete 6. The method of claim 5,
The organic acid is an absorbent hemostatic pad, characterized in that glycolic acid.

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