KR102729703B1 - Method for manufacturing adhesive hemostatic agent mixed with kaolin and cellulose and adhesive hemostatic agent manufactured accordingly - Google Patents

Abstract

The present invention relates to a method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose, and to an adhesive hemostatic agent manufactured thereby, comprising the steps of mixing hyaluronic acid into sterile distilled water, mixing pectin into the mixture, mixing kaolin and cellulose into the mixture, cooling the mixture, applying the mixture, and drying the mixture.
The present invention has excellent rebleeding prevention rate, absorption rate, adhesiveness and biodegradability by mixing hyaluronic acid and pectin in addition to kaolin and cellulose, and has excellent effects in protecting tissue on the wound surface and preventing infection compared to existing pad-type hemostatic agents, and has the effect of preventing a patient from being put at risk due to excessive bleeding.

Description

Method for manufacturing an adhesive hemostatic agent mixed with kaolin and cellulose and an adhesive hemostatic agent manufactured accordingly {METHOD FOR MANUFACTURING ADHESIVE HEMOSTATIC AGENT MIXED WITH KAOLIN AND CELLULOSE AND ADHESIVE HEMOSTATIC AGENT MANUFACTURED ACCORDINGLY}

The present invention relates to a method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose, and to an adhesive hemostatic agent manufactured thereby. More specifically, the present invention relates to a method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose, which can be immediately attached and used in an emergency situation, effectively acts on a bleeding site, and has excellent hemostatic action and hemostatic effect, and to an adhesive hemostatic agent manufactured thereby.

Various hemostatic agents are being developed to stop bleeding and save lives. Various types of hemostatic agents, such as local hemostatic agents, intravenous hemostatic agents, and surgical hemostatic agents, are used depending on the situation. They are used in various forms such as bandages, powders, gels, and injections, and stop bleeding through various modes of action such as platelet activation, clotting factor activation, and fibrin network formation.

Hemostatic agents contain a variety of ingredients that enhance the body's natural hemostasis process. Collagen provides a scaffold that promotes platelet adhesion and aggregation, which is important for clot formation. Gelatin absorbs blood and body fluids and swells to form a physical barrier. Gelatin can absorb up to 45 times its weight in blood. Cellulose forms a gel-like clot when in contact with blood, creating a barrier. Chitosan is derived from chitin and promotes blood clotting by promoting the aggregation of red blood cells and platelets. Thrombin is an enzyme that converts fibrinogen to fibrin, forming a stable clot. Kaolin is a soft, white or nearly white clay found in nature, composed primarily of minerals such as aluminum and silicon. Kaolin is widely used in medical applications to promote blood clotting and control bleeding, particularly by activating factor XII, a key protein in the coagulation pathway, which initiates the clotting process more quickly and effectively. Kaolin is considered a safe and effective hemostatic agent. The risk of adverse immune responses is reduced because foreign proteins are not introduced into the body. Kaolin is an essential component of modern hemostatic agents due to its ability to effectively and safely promote coagulation.

Hemostatic agents such as the above are important in both surgical and emergency situations to control bleeding and ensure patient stability.

However, conventional film-type hemostatic agents containing these ingredients have various problems and limitations.

Patent registration No. 10-1876196 (Medical material manufactured using collagen and its manufacturing method) is characterized by including the steps of preparing collagen using distilled water as a solvent, filling the prepared collagen into a syringe and then radiating it through a syringe needle, immediately immersing or exposing the radiated collagen to a cross-linking mixture containing a hyperosmotic agent and a cross-linking agent, removing and washing the collagen after cross-linking is complete, and removing and drying the collagen after washing is complete.

Many existing hemostatic agents, including collagen-based hemostatic agents such as those described in Patent No. 10-1876196, have limited effectiveness in rapidly stopping bleeding. This can be particularly problematic in critical medical situations where immediate hemostasis is needed to prevent serious bleeding and complications.

Patent No. 10-1876196 is thick and tends to take a long time to dissolve in the body. The longer the dissolution time, the longer the healing process can be delayed and the residual material can increase the risk of infection or other complications. The residual material can cause inflammation and hinder healing.

Therefore, there is a demand for a film-type adhesive hemostatic agent that has a fast hemostasis rate, can be administered accurately and easily regardless of the site of use, has a simple method of use, and is reusable.

Republic of Korea Patent No. 10-1876196 Republic of Korea Patent No. 10-1791893 Republic of Korea Patent No. 10-2189877 Republic of Korea Publication Patent No. 10-2021-0018183

The present invention is intended to solve the above-mentioned problems, and aims to provide a method for manufacturing an adhesive hemostatic agent mixed with kaolin and cellulose, which has excellent adhesive strength and a fast hemostasis speed, thereby shortening the hemostasis time compared to existing film-type hemostatic agents, and which is capable of preventing the risk of infection or other complications by quickly decomposing and absorbing, thereby eliminating the need for worrying about residues remaining, and an adhesive hemostatic agent manufactured thereby.

In addition, the technical problems to be achieved by the present invention are not limited to the technical problems mentioned above, and other technical problems not mentioned can be clearly understood by a person having ordinary skill in the technical field to which the present invention belongs from the description below.

In order to achieve the above-described purpose, the method for manufacturing an adhesive hemostatic agent mixed with kaolin and cellulose according to the present invention comprises the steps of mixing hyaluronic acid into sterile distilled water, mixing pectin into the mixture, mixing kaolin and cellulose into the mixture, cooling the mixture, applying the mixture, and drying the mixture.

The step of mixing the hyaluronic acid is to stir the hyaluronic acid using an ultrasonic stirrer at 400 to 500 rpm for 10 to 20 minutes at 40 to 50°C.

The step of mixing the above pectin is to stir the pectin with a magnetic stirrer at 100 to 200 rpm for 30 to 40 minutes at 40 to 60°C.

It is important to maintain a pH of 3.5 to 6.5 during the step of mixing the pectin.

The step of mixing the above kaolin and cellulose is performed by stirring the kaolin and cellulose using an ultrasonic stirrer at 500 to 600 rpm for 50 to 60 minutes at 50°C to 60°C.

And the step of mixing kaolin and cellulose is characterized by mixing 0.1 to 5 parts by weight of hyaluronic acid, 1 to 5 parts by weight of pectin, 0.1 to 3 parts by weight of kaolin, and 4 to 8 parts by weight of cellulose with respect to 100 parts by weight of sterilized distilled water.

The above cooling step is performed by stirring the mixture with a magnetic stirrer at 200 to 300 rpm for 20 to 30 minutes at 20 to 25°C.

The above-mentioned applying step applies the cooled mixture onto the substrate to a thickness of 0.5 to 2 mm.

The above drying step is to dry the substrate to which the hemostatic agent has been applied in a drying room set to 30°C to 50°C for 1 to 3 hours.

In order to achieve the above-mentioned purpose, an adhesive hemostatic agent mixed with kaolin and cellulose according to the present invention can be manufactured by any one of the above methods.

As described above, the present invention having the above-described configuration is easy to use, allowing rapid use in emergency situations, and has a fast hemostasis speed, thereby shortening the hemostasis time compared to existing hemostatic agents.

And by mixing hyaluronic acid and pectin in addition to kaolin and cellulose, it has excellent hemostasis speed, rebleeding prevention rate, absorption rate, adhesiveness and biodegradability, and there is no need to worry about residues, so it is more effective in protecting the tissue on the wound surface and preventing infection than existing pad-type hemostatic agents, and it has the effect of preventing situations where the patient is put at risk due to excessive bleeding.

Figure 1 is a flow chart showing the step-by-step method for manufacturing an adhesive hemostatic agent mixed with kaolin and cellulose of the present invention.
Figure 2 is a drawing showing the results of a hemostasis speed test according to examples and comparative examples of an adhesive hemostatic agent manufactured according to a method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose of the present invention.
Figure 3 is a drawing showing the results of a test on the prevention of rebleeding according to examples and comparative examples of an adhesive hemostatic agent manufactured according to a method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose of the present invention.
Figure 4 is a drawing showing the results of an absorption rate test according to examples and comparative examples of an adhesive hemostatic agent manufactured according to a method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose of the present invention.
Figure 5 is a drawing showing the results of an adhesive strength test according to examples and comparative examples of an adhesive hemostatic agent manufactured according to a method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose of the present invention.
FIG. 6 is a drawing showing the results of a biodegradability test according to examples and comparative examples of an adhesive hemostatic agent manufactured according to a method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose of the present invention.

The advantages and features of the present invention and the methods for achieving them will become apparent with reference to the embodiments described below in detail together with the accompanying drawings.

However, the present invention is not limited to the embodiments disclosed below, but may be implemented in various different forms.

The embodiments herein are provided so that this disclosure will be complete and will fully convey the scope of the invention to those skilled in the art.

And, the present invention is defined only by the scope of the claims.

Accordingly, in some embodiments, well-known components, well-known operations, and well-known techniques are not specifically described to avoid obscuring the present invention.

Additionally, throughout the specification, like reference numerals refer to like elements, and the terminology used (or referred to) in this specification is for the purpose of describing embodiments and is not intended to limit the present invention.

In this specification, the singular includes the plural unless the context specifically dictates otherwise, and the mention of components and actions as “including (or comprising)” does not exclude the presence or addition of one or more other components and actions.

Unless otherwise defined, all terms (including technical and scientific terms) used herein may be used in a commonly understood sense by a person of ordinary skill in the art to which the present invention belongs.

Additionally, terms defined in commonly used dictionaries are not to be interpreted ideally or excessively unless they are defined otherwise.

Hereinafter, a preferred embodiment of the present invention will be described with reference to the attached drawings.

Referring to FIGS. 1 to 6, the method for manufacturing an adhesive hemostatic agent mixed with kaolin and cellulose according to the present invention is as follows.

First, add hyaluronic acid to the sterilized distilled water in the mixing tank and mix (S10).

Hyaluronic acid is a type of polysaccharide called glycosaminoglycan (GAG), and is a substance that is abundantly present in our skin, joints, cartilage, and eyes. Hyaluronic acid is famous for its excellent moisturizing properties, and plays an important role in performing various biological functions such as maintaining skin elasticity, reducing wrinkles, and lubricating joints.

And hyaluronic acid is known to promote platelet aggregation by binding to receptors on the platelet surface. Platelet aggregation plays an important role in the blood clotting process and helps prevent bleeding. Hyaluronic acid has a vasoconstrictive effect, which helps reduce the amount of bleeding by constricting the blood vessels at the bleeding site.

At this time, mix hyaluronic acid in sterile distilled water and stir with an ultrasonic stirrer at 400 to 500 rpm for 10 to 20 minutes at 40 to 50°C.

Ultrasonic energy creates microscopic vibrations within the mixture, which helps to evenly disperse the hyaluronic acid molecules. This reduces the turbidity of the mixture, prevents clumping, and improves product quality.

Ultrasonic energy can cut the molecular chains of hyaluronic acid to reduce its molecular weight. This can be used to reduce the viscosity of hyaluronic acid, promote skin absorption, and be useful in formulation development. This sonication can enhance the bioactivity of hyaluronic acid.

The temperature range of 40℃ to 50℃ is an appropriate temperature range for increasing solubility while minimizing the decomposition of hyaluronic acid.

If the stirring temperature is lower than 40℃, hyaluronic acid may not obtain the desired viscosity and uniformity. This may result in inconsistent mixing with kaolin and cellulose, which may reduce the adhesive properties and reduce the hemostatic effect. On the contrary, if the temperature exceeds 50℃, hyaluronic acid may decompose or denature, losing its efficacy and changing its chemical structure. This may impair the stability and function of the hemostatic agent.

A speed of 400 to 500 rpm is an appropriate speed to effectively disperse hyaluronic acid molecules while minimizing the temperature rise of the solution. It takes 10 to 20 minutes to sufficiently disperse most hyaluronic acid molecules.

Stirring at speeds lower than 400 rpm can result in incomplete mixing, which can lead to phase separation or uneven distribution of components. This can reduce the adhesive strength and overall efficacy of the hemostatic agent. On the other hand, stirring at speeds higher than 500 rpm can result in excessive air injection or foaming, which can lead to the introduction of air bubbles into the mixture. This can compromise the structural integrity of the final product and reduce the adhesive strength.

If the stirring time is less than 10 minutes, the mixture will not reach the desired consistency, making the hemostatic agent less effective in adhering to the tissue and stopping bleeding. If the stirring time exceeds 20 minutes, excessive processing may cause the hyaluronic acid molecules to decompose, reducing the biocompatibility and performance of the hemostatic agent.

Add pectin to the mixture (S20).

Pectin, a natural polysaccharide found in plant cell walls, plays an important role in improving the properties of adhesive hemostatic agents. Pectin has intrinsic hemostatic properties, which helps blood to clot quickly and reduce bleeding.

Biocompatibility and hydrogel forming ability make it an effective component for rapidly stopping bleeding. Pectin improves the adhesion of the hemostatic agent to the wound site, ensuring that the hemostatic agent stays in place and provides an effective coverage. This is important for maintaining a stable environment for blood clotting and tissue repair. Pectin contributes to the flexibility of the hemostatic film or hydrogel, providing more comfort to the patient and reducing the risk of irritation or damage to surrounding tissue.

Because pectin is biodegradable, the hemostatic agent naturally breaks down over time without causing side effects or requiring removal. This improves patient safety and comfort.

When combined with other ingredients, such as cellulose, pectin can enhance the mechanical strength of composite hemostatic agents, ensuring that they remain intact and functional during the healing process.

Pectin is a very beneficial component that improves the hemostatic effect, adhesiveness, flexibility, biodegradability and mechanical strength of adhesive hemostatic agents.

At this time, pectin is stirred with a magnetic stirrer at 100 to 200 rpm for 30 to 40 minutes at 40 to 60°C.

The temperature range of 40℃ to 60℃ is the temperature condition necessary to effectively dissolve pectin while preventing thermal decomposition. If the temperature is lower than 40℃, pectin may not dissolve properly and may not be completely mixed with kaolin and cellulose, and if it is higher than 60℃, pectin may be decomposed due to excessive heat, changing the molecular structure and reducing the gelation and adhesive properties.

Stirring at a speed lower than 100 rpm may result in incomplete mixing, and stirring at a speed higher than 200 rpm may cause air bubbles to form in the mixture, resulting in foaming. Maintaining these stirring conditions will ensure uniform mixing and prevent pectin from agglomerating in the solution.

Mix the solution for at least 30 minutes to ensure that the pectin is completely dissolved and evenly distributed in the hemostatic agent. However, mixing for more than 40 minutes may cause denaturation of the pectin molecules and weaken the adhesive properties.

And maintaining a pH of 3.5 to 6.5 while mixing pectin is important for several reasons related to the stability, solubility, and functionality of pectin in the solution.

Pectin is most stable in the pH range of 3.5 to 6.5. Outside this range, quality deteriorates, gelling properties are lost, and functionality is impaired.

The solubility of pectin is optimal in this pH range. At pH levels below 3.5, the acidic environment may cause pectin to precipitate. At pH levels above 6.5, the basic environment may lead to deesterification and gel weakening.

Acids or bases may be added to ensure a pH of 3.5 to 6.5 is maintained while mixing the pectin.

Kaolin and cellulose are mixed into the mixture (S30).

Kaolin is a naturally occurring hydrous aluminum silicate, white or milky white powder with a chemical composition of Al2Si2O5(OH)4 containing pyrophyllite.

These kaolins can promote blood clotting by interacting with Factor XII (Hageman Factor), a plasma protein present in the blood.

Additionally, kaolin plays a role in causing transformation by activating Factor XII, Factor XI (thromboplastin precursor), and prekallikrein.

In particular, Factor XII is involved in activation, and kaolin increases the sensitivity of kallikreene, a plasma component of Factor XII, which significantly accelerates the activation rate, thereby promoting blood coagulation and improving the hemostatic effect of wounds.

Cellulose is a natural polymer carbohydrate composed of D-glucose units linked by β-1,4-linkages. Cellulose fibers bind to the surface of platelets, promote platelet aggregation, and activate blood clotting factors to promote clot formation. Cellulose has high absorbency, so it absorbs blood and body fluids at the site of bleeding, helping clot formation and minimizing blood loss.

Kaolin and cellulose exhibit hemostatic effects through the following mechanisms:

Kaolin binds to the platelet surface to promote platelet aggregation and activates blood clotting factors to promote clot formation. Kaolin's high absorbency absorbs blood and body fluids at the site of bleeding, helping clot formation and minimizing blood loss. Cellulose suppresses inflammatory responses and promotes tissue regeneration to help wound healing after hemostasis.

The higher the kaolin content, the faster the blood coagulation rate and the higher the absorption rate. However, the hemostatic agent may become too hard and difficult to apply to the wound site. The higher the cellulose content, the more flexible and biocompatible the hemostatic agent is. However, the blood coagulation rate and absorption rate may decrease.

At this time, kaolin and cellulose are stirred at 50 to 60°C with an ultrasonic stirrer at 500 to 600 rpm for 50 to 60 minutes.

If the temperature is lower than 50℃, the mixing efficiency may decrease, and if it is higher than 60℃, the kaolin or cellulose may decompose. Since the temperature may increase due to the ultrasonic stirring itself, the temperature should be continuously monitored and adjusted as necessary.

If the stirring speed is slower than 500 rpm, the mixing is uneven, and if the stirring speed is faster than 600 rpm, there is a problem of damage to the cellulose fibers.

If the mixing time is too short, the reaction will be incomplete and the mixing will be uneven, which may affect the overall efficacy and performance of the hemostatic agent. However, excessive stirring may damage the cellulose fibers, so care should be taken not to stir for more than 60 minutes.

The composition ratio of the ideal mixtures is as follows.

Mix 0.1 to 5 parts by weight of hyaluronic acid, 1 to 5 parts by weight of pectin, 0.1 to 3 parts by weight of kaolin, and 4 to 8 parts by weight of cellulose with 100 parts by weight of sterilized distilled water.

Sterile distilled water is the basic solvent of hemostatic agents, dissolving other ingredients and maintaining the formulation. If the concentration of hyaluronic acid is lower than 0.1, the adhesiveness and moisture supply properties may be reduced, which may reduce the hemostatic performance. If the concentration exceeds 5, the viscosity increases significantly, making the formulation difficult to apply and potentially reducing the wound penetration ability.

Pectin concentrations below 1 may impair gel formation, resulting in poor structural integrity and reduced hemostatic efficacy. And concentrations above 5 may result in gels becoming too hard, making them less applicable and adaptable to the wound surface. In addition, high pectin levels may result in rapid gelation, making it difficult to mix evenly.

Kaolin has little effect when the concentration is lower than 0.1, and when the concentration exceeds 3, precipitation occurs and the distribution is uneven, resulting in inconsistent hemostatic effects. Cellulose has a reduced structural integrity and absorption capacity when the concentration is lower than 4, which may weaken the hemostatic effect, and when the concentration exceeds 8, the viscosity increases significantly, making the preparation too thick and difficult to apply.

Cool the mixture (S40).

Specifically, the mixture is stirred with a magnetic stirrer at 200 to 300 rpm for 20 to 30 minutes at 20 to 25°C.

If the stirring speed is less than 200 rpm, the components may not be properly mixed, and kaolin and cellulose may not be well combined with the base material. If the stirring speed exceeds 300 rpm, air bubbles may be introduced into the mixture, which may weaken the structural integrity of the hemostatic agent and reduce tissue adhesion and bleeding control effects.

If the stirring time is less than 20 minutes, the ingredients may not be homogeneous. If the stirring time exceeds 20 minutes, excessive stirring may cause bubbles to form, which may deteriorate the quality of the mixture. A water bath or cooler may be used for cooling.

Apply the mixture (S50).

The cooled mixture is applied to the substrate with a thickness of 0.5 to 2 mm. A thin, uniform film can be formed on the substrate using casting or spraying techniques. Non-stick substrates such as silicone or Teflon are used so that the dried film can be easily removed.

If the film thickness exceeds 2 mm, blood clotting is delayed, blood absorption is reduced, and the effect of quickly stopping bleeding is reduced. If the film thickness is thinner than 0.5 mm, it does not form a stable barrier, which reduces mechanical support and fails to obtain sufficient hemostatic effect.

Maintaining it within the range of 0.5 to 2 mm optimizes the performance of the hemostatic agent, allowing for rapid and effective blood clotting.

Dry the mixture (S60).

The substrate to which the hemostatic agent has been applied is dried in a drying room set to 30°C to 50°C for 1 to 3 hours. The drying time varies depending on the film thickness, but 1 to 3 hours is generally sufficient.

Finally, package and sterilize.

Once drying is complete, carefully peel the film off the substrate and cut it into the desired shape or size.

Appropriate packaging materials that can maintain the sterilization status of the product after sterilization must be selected. During the sterilization process, all forms of microorganisms must be completely eliminated to ensure complete sterilization of the product. After sterilization, packaged products must be stored in a clean environment.

Examples and Comparative Examples

Hereinafter, the present invention will be specifically described with examples and comparative examples. A person skilled in the art to which the present invention pertains can change the present invention into various other forms other than the compositions described in the examples below, and the following examples are only intended to illustrate the present invention and should not be construed as limiting the scope of the technical idea of the present invention to the scope of the examples below.

Example 1

Add 3g of hyaluronic acid to 100g of distilled tangerine water in a mixing tank and stir at 450rpm for 20 minutes with an ultrasonic stirrer at 45℃. Then, add 3g of pectin and stir at 150rpm for 40 minutes with a magnetic stirrer at 50℃. During the stirring of the pectin, monitor the pH value in real time using a pH meter to maintain pH 5.

Then, 2 g of kaolin and 6 g of cellulose are stirred at 550 rpm for 55 minutes using an ultrasonic stirrer at 55°C. Then, the mixture is stirred at 250 rpm for 25 minutes using a magnetic stirrer at 20°C and cooled.

After cleaning the substrate surface, apply the cooled mixture. The thickness should be approximately 1 mm overall.

The substrate to which the hemostatic agent has been applied is dried in a drying room set at 40°C for 2 hours.

Example 2

The same procedure as Example 1 was followed, except that 5 g of kaolin and 2 g of cellulose were added and mixed.

Comparative Example 1

The procedure was the same as Example 1 except that 4 g of hyaluronic acid was added without mixing pectin.

Comparative Example 2

The remainder was performed in the same manner as Example 1, except that 8 g of cellulose was added without mixing in hyaluronic acid.

Comparative Example 3

7 g of pectin was added, and the remainder was performed in the same manner as in Example 1.

[Experimental example]

Hemostasis rate test

Twelve-week-old SD male rats were anesthetized with Avertin anesthesia. After anesthesia, the femoral artery was cut to induce bleeding. A hemostatic agent was applied to the bleeding site and pressure was applied. The time until bleeding stopped was measured with a stopwatch. The average hemostasis time was calculated using multiple samples.

Rebleeding prevention rate test

Twelve-week-old SD male rats were anesthetized with Avertin anesthesia. The femoral artery was cut to induce bleeding. A hemostatic agent was applied to the bleeding site and pressure was applied to stop the bleeding. After hemostasis was completed, the surgical site was observed at regular intervals to record whether rebleeding occurred. The rate of no rebleeding was calculated.

Absorption rate test

Twelve-week-old SD male rats were anesthetized with Avertin anesthesia. Blood was obtained through cardiac blood collection. The blood was placed in a tube containing an absorbable hemostatic agent. After a certain period of time, the amount of blood remaining in the tube was measured to calculate the amount of blood absorbed by the hemostatic agent. The average absorption rate was calculated using multiple samples.

Adhesion Test

Twelve-week-old SD male rats were anesthetized with Avertin anesthesia. The hair of the male rats was shaved, and the skin surface was cleaned. Light pressure was applied for a certain period of time to ensure that the film-type hemostatic agent was completely adhered to the skin.

A pin was attached to the surface of the film-shaped hemostatic agent, and the time taken for it to fall off at a certain angle was measured. The average adhesive strength was calculated by measuring it several times in the same way. The longer the time taken for it to fall off, the stronger the adhesive strength.

The average adhesion was calculated using multiple samples.

Biodegradability Test

The film-shaped hemostatic agent was crushed into small pieces. An artificial composting environment was created that maintained the conditions of 35℃, 50% humidity, and pH 6. The crushed hemostatic agent was placed in the artificial composting environment and allowed to decompose for two months.

The degree of degradation was assessed by measuring the weight loss and carbon emissions of the samples every two weeks. The average biodegradability was calculated using multiple samples.

[Experimental Results]

Referring to Figure 2, it appears that kaolin played an important role in increasing the hemostasis speed. It was confirmed that Example 2 had a slightly faster hemostasis speed than Example 1 because the kaolin content was higher.

In the case of Comparative Example 2 and Comparative Example 3, the hemostasis speed was not bad. Comparative Example 2 did not mix hyaluronic acid, and hyaluronic acid did not seem to have a significant effect on the hemostasis speed. Comparative Example 3 had a high pectin content, and pectin was confirmed to have a positive effect on the hemostasis speed. Comparative Example 1 did not mix pectin, and considering that the hemostasis speed was relatively slow, it can be seen that pectin affects the hemostasis speed.

Referring to Figure 3, it was confirmed that the presence or absence of cellulose mixing was important in the case of the rebleeding prevention rate. The fact that Comparative Example 2 had a better rebleeding prevention rate than Example 2 and Comparative Example 1 seems to be an effect that occurred by adding a large amount of cellulose without mixing hyaluronic acid.

Comparative Example 1 added both cellulose and hyaluronic acid, while Comparative Example 2 did not add hyaluronic acid and instead added more cellulose. Ultimately, it appears that cellulose is more effective in preventing rebleeding.

Comparative Example 3 contained cellulose, but the amount of pectin added was so large that the effect of preventing rebleeding seemed to be reduced.

However, considering that the rebleeding prevention effect of Example 1 is good, the content of cellulose is also important, but kaolin and hyaluronic acid also seem to have a good effect in preventing rebleeding, and it can be seen that mixing hyaluronic acid, pectin, kaolin, and cellulose and the mixing ratio of each component are important.

Referring to Figure 4, it appears that cellulose also played an important role in the case of absorption rate. Comparative Example 2 added a lot of cellulose without mixing hyaluronic acid, and when compared to Comparative Example 1 where both hyaluronic acid and cellulose were added, the absorption rate was better, indicating that cellulose had a better absorption effect than hyaluronic acid.

Considering that Comparative Example 3 has a better absorption rate than Comparative Example 1, it appears that pectin has a better effect on the absorption rate than hyaluronic acid.

However, considering that the absorption rate effect of Example 1 is good, it can be seen that mixing hyaluronic acid, pectin, kaolin, and cellulose and the mixing ratio of each component are important.

Referring to Figure 5, it was shown that hyaluronic acid and pectin played an important role in increasing the adhesive strength of the hemostatic agent.

The adhesive strengths of Examples 1, 2, and Comparative Example 3, which contained both hyaluronic acid and pectin, were good, and among them, Comparative Example 3, which had a high pectin content, was the best.

The adhesive strength of Comparative Examples 1 and 2 was not good. It seems that the adhesive strength was affected because Comparative Example 1 did not mix pectin, and Comparative Example 2 did not mix hyaluronic acid.

Comparative Example 2 did not have better adhesive strength than Comparative Example 1, and it was found that adhesive strength problems occurred when hyaluronic acid was not mixed.

Referring to Figure 6, it was shown that cellulose and pectin played an important role in promoting biodegradability.

Example 1 had the best biodegradability, and Comparative Example 3 showed a biodegradability effect similar to that of Example 1. From this, it can be seen that cellulose and pectin have a significant effect on biodegradability.

Comparative Example 2 contained both cellulose and pectin, but did not mix in hyaluronic acid, so its biodegradability was relatively poor. Comparative Example 1 did not mix in pectin, so its biodegradability was the worst.

When compared based on the ingredient content, Comparative Example 3 contained more pectin than Example 1 while having the same other ingredients. However, considering that Example 1 has better biodegradability, it can be seen that the mixing ratio of cellulose, pectin, hyaluronic acid, and kaolin is important.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, it will be readily apparent to those skilled in the art that various modifications and variations may be made therein without departing from the spirit and scope of the invention as set forth in the appended claims.

Claims (10)

Step (S10) of mixing hyaluronic acid into sterilized distilled water using an ultrasonic stirrer;
Step of mixing pectin into the above mixture (S20);
A step of mixing kaolin and cellulose into the mixture using an ultrasonic stirrer (S30);
Step of cooling the above mixture (S40);
Step of applying the above mixture (S50); and
Including a step of drying the above mixture (S60);
The step of mixing the above kaolin and cellulose (S30) is
Kaolin and cellulose were stirred at 50 to 60°C with an ultrasonic stirrer at 500 to 600 rpm for 50 to 60 minutes,
The step of mixing the above kaolin and cellulose (S30) is
A method for producing an adhesive hemostatic agent mixed with kaolin and cellulose, characterized in that 0.1 to 5 parts by weight of hyaluronic acid, 1 to 5 parts by weight of pectin, 0.1 to 3 parts by weight of kaolin, and 4 to 8 parts by weight of cellulose are mixed with 100 parts by weight of the above sterilized distilled water.
In claim 1,
The step of mixing the above hyaluronic acid (S10) is as follows:
A method for producing an adhesive hemostatic agent by mixing kaolin and cellulose, characterized in that hyaluronic acid is stirred at 400 to 500 rpm for 10 to 20 minutes using an ultrasonic stirrer at 40 to 50°C.
In claim 1,
The step of mixing the above pectin (S20) is
A method for producing an adhesive hemostatic agent by mixing kaolin and cellulose, characterized in that pectin is stirred at 100 to 200 rpm for 30 to 40 minutes with a magnetic stirrer at 40 to 60°C.
In claim 3,
The step of mixing the above pectin (S20) is
A method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose, characterized in that the pH is maintained at 3.5 to 6.5 while mixing pectin.
delete delete In claim 1,
The above cooling step (S40) is
A method for producing an adhesive hemostatic agent by mixing kaolin and cellulose, characterized in that the mixture is stirred with a magnetic stirrer at 200 to 300 rpm for 20 to 30 minutes at 20 to 25°C.
In claim 1,
The above-mentioned applying step (S50) is
A method for manufacturing an adhesive hemostatic agent by mixing kaolin and cellulose, characterized in that the cooled mixture is applied to a substrate at a thickness of 0.5 to 2 mm.
In claim 1,
The above drying step (S60) is
A method for manufacturing an adhesive hemostatic agent using a mixture of kaolin and cellulose, characterized in that the substrate to which the hemostatic agent has been applied is dried in a drying room set to 30°C to 50°C for 1 to 3 hours.
An adhesive hemostatic agent mixed with kaolin and cellulose, characterized in that it is manufactured by the method of any one of claims 1 to 4 and claims 7 to 9.