KR20230091706A - Anti-adhesive powder and manufacturing method for anti-adhesive powder - Google Patents

Abstract

The present invention relates to an anti-adhesion agent powder and a method for manufacturing an anti-adhesion agent powder. The present invention is to provide the anti-adhesion agent powder, which contains carboxymethyl starch (CMS), which is made from a cross-linked starch powder, and can implement a sufficient anti-adhesion function during a period when tissue wounds heal after surgery by controlling the degree of crosslinking and hydrophilicity of natural polymer raw materials.

Description

Anti-adhesive powder and manufacturing method of anti-adhesive powder {ANTI-ADHESIVE POWDER AND MANUFACTURING METHOD FOR ANTI-ADHESIVE POWDER}

The present invention relates to an anti-adhesion agent powder and a method for producing the anti-adhesion agent powder.

Adhesion of organs and tissues that occurs after surgery is a natural phenomenon that occurs in the process of proliferating and regenerating damaged tissue cells. Adhesion detachment requires reoperation and can be a life-threatening factor.

There are three main ways to prevent adhesion.

First, there is a method of minimizing tissue damage and adhesion caused by foreign substances due to delicate care and unnecessary procedures during surgery. In the case of careful operation using laparoscopy, minimally invasive surgical technique, or laser technique, it is helpful to prevent adhesion due to the effect of pneumoperitoneum, which minimizes or prevents trauma, exposure to foreign substances, and tissue drying, and helps hemostasis. However, these methods have limitations in that they can reduce but not eliminate adhesion formation.

Second, it is to suppress the pathophysiological process necessary for inflammatory response and adhesion formation with drug treatment based on the adhesion mechanism. As drug preparations, fibrinolytic agents to prevent adhesion formation, anticoagulants, anti-inflammatory agents, antibiotics to prevent infection, and other hormones are used. These medications are not effective in all cases, and have been proven in animal experiments. Some have not yet been proven effective in clinical trials. Most drugs act to interfere with the deposition of fibrin generated during the healing process, which has the side effect of slowing down the healing rate of wounds compared to the anti-adhesion effect. Therefore, the use of drugs to prevent adhesion is limited and requires a lot of attention.

Finally, thirdly, it is widely used in clinical practice as a method of preventing adhesion by blocking contact with surrounding tissues by wrapping or covering the wound using an anti-adhesion barrier after surgery, and its importance is being highlighted. There are solid (endogenous and exogenous), liquid and gel types of anti-adhesion films. The anti-adhesion film serves to block contact between the wound and surrounding tissues by covering or covering the wound by blocking the area where adhesion is expected during the surgical procedure with a physical barrier. A suitable material as an anti-adhesion film should be safe and effective, should not cause an inflammatory reaction or an immune reaction, should not require suturing, and should remain active even in the blood. In addition, it remains during the healing period of damaged tissue and acts to prevent adhesion, but after a certain period of time, it is decomposed or absorbed, so there is no need for separate removal. Substances discharged through metabolism must also be harmless to the human body and have excellent biocompatibility.

In the case of surgical methods that are currently introduced in various ways, naturally occurring adhesions cannot be completely prevented, and in the case of drugs, problems that are easily absorbed and do not properly exert their efficacy remain as homework. In contrast, the anti-adhesion film is widely used in clinical practice because it can fundamentally separate damaged tissues and surrounding tissues, and is known to have relatively superior efficacy compared to other methods. However, currently commercialized solutions, gels, and film-type anti-adhesion films have various types of problems.

Even if the anti-adhesion agent in the form of a solution has a high viscosity, it is difficult to apply it accurately to the wound as it flows down from the body, and it may flow to other parts before performing the anti-adhesion function or be decomposed too early, so the anti-adhesion function is often not performed properly. There are downsides.

Anti-adhesion films in the form of films and membranes have been clinically proven to be most effective and are commercially available, but these products do not adhere well to the surface of organs when applied to internal organs, and even when attached, they remain on the wound due to the movement of the organs. It is reported that the long-term adhesion prevention effect is insufficient due to the problem of not being accurately positioned and recognized as a foreign substance in the tissue itself and clumped together. In addition, film-type products are mainly used only in a limited manner, such as in obstetrics and gynecology or spine surgery, and their shape is deformed or weak, so there are morphological limitations to apply to minimally invasive surgery or laparoscopic surgery, which requires an anti-adhesion film to be inserted through a trocar. big. In order to suppress the movement of the anti-adhesion agent from the application site, it is necessary to suture with the surrounding tissue, and at this time, tissue adhesion frequently occurs at the suture site and it is difficult to introduce it into complex or finely shaped wounds. .

However, despite these disadvantages, it is a reality that there is still no product that can replace it in that it is a form that can definitely provide a physical barrier, one of the principles of anti-adhesion.

Finally, gel-type anti-adhesion agents are being developed as injectable formulations to overcome the disadvantages of film and solution forms. Although the period required for wound healing varies depending on the severity of the wound, it is generally about 7 days. In order to expect an anti-adhesion effect, it is necessary to help the wound area regenerate normally for about 7 days, and the tissue adjacent to the wound It must prevent the formation of fibers and fibrous tissue, and then it must be naturally decomposed, absorbed and eliminated. However, in the case of an anti-adhesion agent in the form of a gel, it is melted and discharged before the wound is healed and does not have enough time to stay in the wound tissue, so it does not show the anti-adhesion effect properly, and non-living materials have problems such as foreign body reaction in vivo. .

Therefore, in order to ensure the anti-adhesion function, there is a need for an anti-adhesion agent of an injectable formulation that has excellent adhesion so that it can be continuously adhered to the wound site during surgery and is suitable for minimally invasive surgery or laparoscopic surgery.

The present invention is to provide an anti-adhesion powder capable of implementing a sufficient anti-adhesion function during the healing period of tissue wounds after surgery by controlling the degree of crosslinking and hydrophilicity of natural polymeric raw materials.

In addition, the present invention is to provide a method for producing the anti-adhesion agent powder having the degree of crosslinking and the degree of hydrophilicity controlled.

However, the problem to be solved by the present invention is not limited to the above-mentioned problem, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

An exemplary embodiment of the present invention includes CarboxyMethyl Starch (CMS) using crosslinked starch powder as a raw material, and the degree of crosslinking calculated by Equation 1 below of the crosslinked starch is 15% An anti-adhesion agent powder having more than 22% and less than:

[Equation 1]

Degree of crosslinking (%) = {(V _A - V _B ) / V _A } X 100

In Equation 1, V _A is the viscosity (cp) of uncrosslinked starch, and V _B is the viscosity (cp) of crosslinked starch.

In addition, an exemplary embodiment of the present invention comprises the steps of obtaining cross-linked starch using a first mixture containing starch and a cross-linking agent; Obtaining carboxymethyl starch using a second mixture comprising the cross-linked starch, carboxylic acid, basic compound and catalyst; And controlling the particle size distribution of the carboxymethyl starch; provides a method for producing an anti-adhesion powder comprising a.

The anti-adhesion powder according to an exemplary embodiment of the present invention can realize sufficient anti-adhesion function during the period required for tissue wound healing after surgery by adjusting the degree of crosslinking and hydrophilicity of the natural polymer raw material.

The anti-adhesion powder according to one embodiment of the present invention can maximize tissue adhesion by forming an anti-adhesion film in vivo immediately after application to a wound.

The anti-adhesion powder according to an exemplary embodiment of the present invention is naturally decomposed and absorbed and discharged after the period required for wound healing, so that systemic reactions (vomiting, fever, digestive symptoms, allergic reactions) and local reactions (edema, fever) , inflammation) can be minimized.

The anti-adhesion powder according to an exemplary embodiment of the present invention is formulated in a powder form and can be accurately sprayed to the wound during laparoscopic and minimally invasive procedures.

The anti-adhesion agent powder according to an exemplary embodiment of the present invention may have excellent gelation strength and viscoelastic properties.

In addition, the method for producing an anti-adhesion agent powder according to an exemplary embodiment of the present invention can easily control the degree of crosslinking and hydrophilicity of the anti-adhesion agent powder to be produced.

Effects of the present invention are not limited to the above-mentioned effects, and effects not mentioned will be clearly understood by those skilled in the art from the present specification and accompanying drawings.

1 is an image showing a schematic diagram of a method for producing an anti-adhesion agent powder according to the present invention.
2 and 3 are images of the anti-adhesion agent powder according to Example 1.
4 and 5 are images showing the particle size distribution of the anti-adhesion powder according to Comparative Example 1 and Example 1.
Figure 6 is an image showing the storage modulus (storage modulus) evaluation results of the anti-adhesion gel layer according to Preparation Example 1 and Preparation Example 2.
7 is an image showing the evaluation results of the viscoelasticity of the anti-adhesion gel layer according to Preparation Example 1 and Preparation Example 2.
8 is an image showing the difference in concentration change after a certain period of time in the enzyme solution of the anti-adhesion agent powder according to Example 1 and Comparative Example 2.

Throughout the present specification, when a certain component is said to "include", it means that it may further include other components without excluding other components unless otherwise stated.

Throughout the present specification, when a member is said to be located “on” another member, this includes not only a case where a member is in contact with another member, but also a case where another member exists between the two members.

Hereinafter, the present invention will be described in more detail.

An exemplary embodiment of the present invention includes CarboxyMethyl Starch (CMS) using crosslinked starch powder as a raw material, and the degree of crosslinking calculated by Equation 1 below of the crosslinked starch is 15% An anti-adhesion agent powder having more than 22% and less than:

[Equation 1]

Degree of crosslinking (%) = {(V _A - V _B ) / V _A } X 100

In Equation 1, V _A is the viscosity (cp) of uncrosslinked starch, and V _B is the viscosity (cp) of crosslinked starch.

According to an exemplary embodiment of the present invention, the carboxymethyl starch obtained from the cross-linked starch powder is starch, that is, cross-linked starch is obtained through etherification between starch molecules, and the ester of the cross-linked starch is obtained. It may be obtained by carboxymethylating the hydroxyl group of starch crosslinked through esterification. Specifically, the crosslinked starch may be to control the degree of crosslinking of the crosslinked starch through the control of the etherification reaction, and may be to control the hydrophilicity of the carboxymethyl starch through the control of the esterification reaction. . More specifically, the degree of crosslinking of the crosslinked starch may be controlled to control the biodegradation rate of the anti-adhesion agent powder, and the anti-adhesion function of the anti-adhesion agent powder may be controlled by adjusting the hydrophilicity of the carboxymethyl starch.

According to an exemplary embodiment of the present invention, the degree of crosslinking calculated by Equation 1 of the crosslinked starch is 15% or more and 22% or less, 10% or more and 20% or less, 10% or more 18% or less, 17% or more 22% It may be less than or equal to 17% or more and less than or equal to 20%. When the degree of crosslinking of the crosslinked starch satisfies the above range, when the anti-adhesion agent powder is applied to the object, the gelation strength and viscoelastic properties of the gel layer formed by gelation by moisture at the application site may be excellent.

According to an exemplary embodiment of the present invention, the degree of crosslinking of the crosslinked starch may be calculated from the viscosity of uncrosslinked starch (V _A ) and the viscosity of crosslinked starch (V _B ), and the viscosity may be calculated by a method known in the art. may be measured by Specifically, the uncrosslinked starch may refer to starch that has not undergone separate crosslinking (etherification reaction) or hydrophilization (esterification reaction), and the crosslinked starch is crosslinked through an etherification reaction between starch molecules. It may mean starch.

According to an exemplary embodiment of the present invention, the crosslinking degree of the crosslinked starch may not change by the esterification reaction, and the crosslinking degree of the crosslinked starch is the crosslinking degree of the carboxymethyl starch using the crosslinked starch powder as a raw material and may be the same. Specifically, since the anti-adhesion agent powder according to the present invention can minimize additional cross-linking by esterification according to the manufacturing method described later, the cross-linking degree of carboxymethyl starch may be derived from the cross-linking degree of cross-linked starch. More specifically, the anti-adhesion agent powder according to the present invention may minimize additional changes in crosslinking degree occurring in the esterification process by performing crosslinking prior to esterification of starch.

According to an exemplary embodiment of the present invention, the anti-adhesion agent powder may be formulated as a powder form of the anti-adhesion agent. Specifically, the anti-adhesion agent powder formulated in a powder form may be sprayed onto a wound site requiring adhesion prevention by a spray device, and may be accurately sprayed onto a wound site even during laparoscopic and minimally invasive procedures. That is, when the anti-adhesion agent powder formulated in powder form is applied to an object, it can be gelled by moisture at the application site to form a gel layer, and the gel layer maximizes tissue adhesion, so that the anti-adhesion agent in solution form has can solve the problem. In addition, the gel layer has excellent gelation strength and viscoelastic properties, so that a sufficient anti-adhesion function can be implemented.

According to an exemplary embodiment of the present invention, the degree of substitution of the carboxymethyl group calculated by Equation 2 below of the anti-adhesion agent powder may be 0.6 or more and 0.8 or less:

[Equation 2]

Degree of substitution = (162 X n _COOH ) / {m _dry - (58 X n _COOH )}

In Equation 2, 162 is the molecular weight (g/mol) of anhydrous glucose unit (AGU), n _COOH is the amount of COOH (mol) determined by back titration, and m _dry is the mass (g) of the dried powder sample. , and 58 is the mass increase (g/mol) of the anhydrous glucose unit according to the increase of the carboxymethyl group.

According to an exemplary embodiment of the present invention, m _dry may be calculated by Equation 3 below:

[Equation 3]

m _dry = (1- W _water /100) X m _s

In Equation 3, m _dry is the mass (g) of the dried powder sample, W _water is the moisture content (%) of the powder sample before drying, and m _s is the mass (g) of the powder sample before drying.

According to an exemplary embodiment of the present invention, the degree of substitution of the carboxymethyl group calculated by Equation 2 of the anti-adhesion agent powder is 0.6 or more and 0.75 or less, 0.6 or more and 0.7 or less, 0.65 or more and 0.8 or less, 0.7 or more and 0.8 or less, or 0.65 It may be greater than or equal to 0.75. Specifically, the degree of substitution of the carboxymethyl group of the anti-adhesion agent powder may be adjusted according to the degree of substitution of the hydroxyl group of the carboxymethyl starch with the carboxylmethyl group. That is, by adjusting the degree of substitution of the carboxymethyl starch contained in the anti-adhesion agent powder, the degree of substitution of the carboxymethyl group of the anti-adhesion agent powder can be adjusted, thereby controlling the gelation rate and tissue adhesion of the anti-adhesion agent powder. it may be When the degree of substitution of the carboxymethyl group of the anti-adhesion agent powder satisfies the above range, when the anti-adhesion agent powder is applied to an object, it absorbs moisture present in the application site after application to the wound and gels within an appropriate time to form a gel layer. can do. That is, since the gel layer can function as an anti-adhesion film with maximized tissue adhesion, it is possible to form an anti-adhesion film on a desired site through spraying the anti-adhesion agent powder.

According to an exemplary embodiment of the present invention, the hydrophilicity of the anti-adhesion agent powder may be adjusted according to the number of glucose units substituted with carboxymethyl groups and the number of glucose units subjected to esterification. Specifically, when the glucose unit is substituted with a carboxymethyl group, the hydrophilicity may decrease, and when the glucose unit substituted with a carboxymethyl group undergoes an esterification reaction with alcohol, the hydrophilicity of the anti-adhesion agent powder increases it could be

According to an exemplary embodiment of the present invention, the anti-adhesion agent powder may further include a crosslinking agent, and the crosslinking agent is phosphorus oxychloride (POCl ₃ ), epichlorohydrin (1-chloro-2,3-epoxypropane), Among sodium trimetaphosphate ((NaPO- ₃ ) _3-- ) _, sodium metaphosphate, citric acid, succinic acid, sodium trimetaphosphate (STMP), sodium tripolyphosphate (SSTP) and citrus oil It may contain at least any one. Specifically, the crosslinking agent may include at least one of epichlorohydrin, citric acid, and citrus oil. When using the above-mentioned kind of crosslinking agent, the formation of the crosslinked starch may be facilitated, and the degree of crosslinking of the carboxymethyl starch may be easily controlled.

According to an exemplary embodiment of the present invention, the anti-adhesion powder may further include additives, and the additives include salicin, curcumin, genipin, allicin, lycopene, and progenonine. And it may include at least one of scopoletin. In the case of including the aforementioned type of additive, an additional effect may be imparted to the anti-adhesion agent powder in addition to the anti-adhesion effect. For example, salicin may have anti-inflammatory and analgesic action as willow bark extract, curcumin may have anti-inflammatory action as Curcuma Longa Linn root extract, and genipin may have hemostatic and anti-inflammatory action as gardenia fruit extract. may be doing

According to one embodiment of the present invention, the anti-adhesion powder may have a controlled particle size distribution. Through this, by adjusting the hydrophilicity of the anti-adhesion agent powder, it is possible to implement sufficient anti-adhesion function during the period required for tissue wound healing after surgery.

According to an exemplary embodiment of the present invention, the average particle diameter (Dv50) of the anti-adhesion agent powder may be 50 μm or more and 100 μm or less. Specifically, the average particle diameter of the powder may be 50 μm or more and 90 μm or less, 50 μm or more and 80 μm or less, 60 μm or more and 100 μm or less, 70 μm or more and 100 μm or less, or 65 μm or more and 85 μm or less. When the average particle diameter of the above-mentioned range is satisfied, the anti-adhesion agent powder may be accurately sprayed to the wound during laparoscopic and minimally invasive procedures. In addition, the anti-adhesion agent powder can maximize tissue adhesion by forming an anti-adhesion film in vivo immediately after application to a wound in a powder form. In addition, after the period required for wound healing, side effects such as systemic reactions (vomiting, fever, digestive symptoms, allergic reactions) and local reactions (edema, heat, inflammation) can be minimized by being naturally decomposed and absorbed and discharged. there is.

According to one embodiment of the present invention, when the anti-adhesion agent powder is applied to an individual, it may be gelated by moisture at the application site to form a gel layer having a storage modulus (G′) of 10 ³ Pa or more. Specifically, when the powder is applied to an object, it is gelled by moisture at the application site and the storage modulus is 1 x 10 ³ Pa or more, 2 x 10 ³ Pa or more, 3 x 10 ³ Pa or more, 4 x 10 ³ Pa or more, or It may form a gel layer of 5 x 10 ³ Pa or more, and may form a gel layer with a gel storage modulus of 1 x 10 ⁵ Pa or less or 1 x 10 ⁴ Pa or less. In this case, the storage modulus may mean gelation strength of the gel layer. When the storage modulus in the above range is satisfied, the anti-adhesion agent powder is easy to control the gelation rate and viscoelastic properties, and has excellent gelation strength and viscoelastic properties, so that the anti-adhesion function is similar to that of film and membrane type anti-adhesion films. can be implemented.

According to one embodiment of the present invention, the storage modulus may be measured through a dynamic vibration test method, and the structural strength of the anti-adhesion gel layer may be controlled by adjusting the storage modulus of the anti-adhesion gel layer. there is. More specifically, the storage modulus (G′) is a property related to the elasticity of the gel layer. As the storage modulus increases, the elastic property of the gel layer increases, and thus the structural strength may increase.

According to one embodiment of the present invention, the anti-adhesion agent powder may be applied to the individual in an amount of 5 parts by weight or more and 10 parts by weight or less based on 100 parts by weight of water in the application area. Specifically, the anti-adhesion agent powder is 5 parts by weight or more and 9 parts by weight or less, 5 parts by weight or more and 8 parts by weight or less, 5 parts by weight or more and 7 parts by weight or less, 6 parts by weight or more 10 It may be applied to the individual in an amount of 7 parts by weight or less, 7 parts by weight or more and 10 parts by weight or less, 6 parts by weight or more and 9 parts by weight or less, or 7 parts by weight or more and 8 parts by weight or less. When the content of the anti-adhesion agent powder in the above range is satisfied, the structural strength of the anti-adhesion gel layer may be adjusted by adjusting the gel storage modulus of the anti-adhesion gel layer formed from the anti-adhesion agent powder. Therefore, it is easy to control the gelation rate and viscoelastic properties of the anti-adhesion agent powder, and the gelation strength and viscoelastic properties implemented are excellent, so that anti-adhesion functions similar to those of anti-adhesion films in the form of films and membranes can be implemented.

One embodiment of the present invention comprises the steps of obtaining cross-linked starch using a first mixture containing starch and a cross-linking agent; Obtaining carboxymethyl starch using a second mixture comprising the cross-linked starch, carboxylic acid, basic compound and catalyst; And controlling the particle size distribution of the carboxymethyl starch; provides a method for producing an anti-adhesion powder comprising a. The manufacturing method of the anti-adhesion agent powder according to an exemplary embodiment of the present invention can easily adjust the hydrophilicity of the anti-adhesion agent powder to be produced.

Hereinafter, a preferred embodiment of the present invention will be described in more detail with reference to the accompanying drawings.

1 is an image showing a schematic diagram of a method for producing an anti-adhesion agent powder according to the present invention.

Referring to FIG. 1, after preparing raw materials, crosslinked starch can be obtained by using a first mixture containing starch and a crosslinking agent. That is, crosslinking (etherification reaction) may be performed using the first mixture. Specifically, it may be to obtain cross-linked starch through etherification between starch molecules included in the first mixture, and to control the degree of cross-linking of the cross-linked starch through control of the etherification reaction. there is. In addition, it may be to control the biodegradation rate of the anti-adhesion agent powder prepared by adjusting the crosslinking degree of the cross-linked starch.

According to an exemplary embodiment of the present invention, the first mixture may include a first organic solvent. That is, obtaining the cross-linked starch; may be to obtain cross-linked starch using a first suspension containing starch, a cross-linking agent and a first organic solvent. Specifically, the first suspension may be reacted by stirring at room temperature and then dried to adjust the moisture content of the first mixture, and the first mixture whose moisture content is adjusted may be pulverized and washed with the first organic solvent. And repeating the drying process may be to adjust the degree of crosslinking of the crosslinked starch.

According to an exemplary embodiment of the present invention, the first organic solvent may be alcohol having 1 to 3 carbon atoms, for example, ethanol. When using the first organic solvent of the above-mentioned type, dissolution and reaction of starch and crosslinking agent may be facilitated, and crosslinked starch may be easily obtained.

According to an exemplary embodiment of the present invention, the starch may be a polymer material of natural origin, and commercially available starches such as potato starch and corn starch may be purified and used. For example, the starch may be starch derived from potato starch.

According to an exemplary embodiment of the present invention, the crosslinking agent is phosphorus oxychloride (POCl ₃ ), epichlorohydrin (1-chloro-2,3-epoxypropane), sodium trimetaphosphate ((NaPO- ₃ ) _3-- ) _, sodium metaphosphate, citric acid, succinic acid, sodium trimetaphosphate (STMP), and citrus oil. Specifically, the crosslinking agent may include at least one of epichlorohydrin, citric acid, and citrus oil. When using the above-mentioned kind of crosslinking agent, the formation of the crosslinked starch may be facilitated, and the degree of crosslinking of the crosslinked starch may be easily controlled.

According to an exemplary embodiment of the present invention, the first mixture may further include an additive, and the additive includes salicin, curcumin, genipin, allicin, lycopene, and progenonine. And it may include at least one of scopoletin. In the case of including the aforementioned type of additive, an additional effect may be imparted to the anti-adhesion agent powder in addition to the anti-adhesion effect. For example, salicin may have anti-inflammatory and analgesic action as willow bark extract, curcumin may have anti-inflammatory action as Curcuma Longa Linn root extract, and genipin may have hemostatic and anti-inflammatory action as gardenia fruit extract. may be doing

According to one embodiment of the present invention, obtaining the cross-linked starch; is to control the degree of cross-linking of the cross-linked starch obtained by adjusting the content, temperature and reaction time of starch and cross-linking agent contained in the first mixture it could be

According to an exemplary embodiment of the present invention, the content of the starch is 50 parts by weight or more and 70 parts by weight or less based on 100 parts by weight of the first mixture, and the content of the crosslinking agent is 10 parts by weight based on 100 parts by weight of the first mixture. It may be more than 25 parts by weight or less. Specifically, the content of the starch is 50 parts by weight or more and 70 parts by weight or less, 50 parts by weight or more and 65 parts by weight or less, 55 parts by weight or more and 70 parts by weight or less, or 55 parts by weight or more 65 parts by weight based on 100 parts by weight of the first mixture. 10 parts by weight or more and 25 parts by weight or less, 10 parts by weight or more and 20 parts by weight or less, 10 parts by weight or more and 15 parts by weight or less, 15 parts by weight or more based on 100 parts by weight of the first mixture. It may be 25 parts by weight or less, or 15 parts by weight or more and 20 parts by weight or less. When the contents of starch and crosslinking agent in the above range are satisfied, the degree of crosslinking of the obtained crosslinked starch can be easily controlled, and when the prepared anti-adhesion agent powder is applied to an object, it is gelated by moisture at the application site to form The gelation strength and viscoelastic properties of the gel layer may be excellent. In addition, it may be easy to control the biodegradation rate of the produced anti-adhesion agent powder.

According to an exemplary embodiment of the present invention, the step of obtaining the crosslinked starch; is dried by stirring the first mixture at room temperature for 18 hours or more and 22 hours or less, and then drying at a temperature of 40 ℃ or more and 60 ℃ or less obtaining a first mixture; And reacting the dried first mixture at a temperature of 110 ℃ or more and 130 ℃ or less for a time of 5 hours or more and 7 hours or less to obtain the cross-linked starch; including, the moisture content of the dried first mixture may be 10 parts by weight or more and 15 parts by weight or less based on 100 parts by weight of the dried first mixture.

When the reaction temperature, time, and water content are within the above-described range, the degree of cross-linking of the obtained cross-linked starch can be easily controlled, and when the prepared anti-adhesion agent powder is applied to an object, it is formed by gelation by moisture at the application site. The gelation strength and viscoelastic properties of the gel layer may be excellent.

According to an exemplary embodiment of the present invention, obtaining the dried first mixture; After stirring the first mixture at room temperature for 18 hours or more and 22 hours or less, drying at a temperature of 40 ℃ or more and 60 ℃ or less Obtaining a dried first mixture; may include. Specifically, the first mixture may be stirred at room temperature for 18 hours or more and 20 hours or less, or 20 hours or more and 22 hours or less, and after the stirring, the temperature is raised to 40 ° C. or more and 50 ° C. or 50 ° C. or more and 60 ° C. or less. It may be to dry at a temperature of. For example, after stirring the first mixture at room temperature for 20 hours, the temperature may be raised to 50 °C and dried. When the above-mentioned temperature and time ranges are satisfied, it may be easier to control the degree of crosslinking of the obtained crosslinked starch, and it may be easier to control the moisture content of the dried first mixture.

According to an exemplary embodiment of the present invention, the step of obtaining the dried first mixture; is by reacting the dried first mixture at a temperature of 110 ℃ or more and 130 ℃ or less for a time of 5 hours or more and 7 hours or less. It may include; obtaining starch. Specifically, the dried first mixture is reacted at a temperature of 110 ° C. or more and 120 ° C. or 120 ° C. or more and 130 ° C. or less for 5 hours or more and 6 hours or less or 6 hours or more and 7 hours or less to obtain the crosslinked starch. it may be For example, the dried first mixture may be reacted at a temperature of 120 ° C. for 6 hours to obtain the cross-linked starch. When the above-described temperature and time ranges are satisfied, the degree of crosslinking of the obtained crosslinked starch can be more easily controlled, and when the prepared anti-adhesion agent powder is applied to an object, the gel layer formed by gelation by moisture at the application site Gelling strength and viscoelastic properties may be excellent.

According to an exemplary embodiment of the present invention, the moisture content of the dried first mixture may be 10 parts by weight or more and 15 parts by weight or less based on 100 parts by weight of the dried first mixture. Specifically, the water content of the dried first mixture is 10 parts by weight or more and 14 parts by weight or less, 10 parts by weight or more and 13 parts by weight or less, 11 parts by weight or more and 15 parts by weight or less, based on 100 parts by weight of the dried first mixture. , 12 parts by weight or more and 15 parts by weight or less, or 12 parts by weight or more and 14 parts by weight or less. When the above-described moisture content is satisfied, it may be easier to control the crosslinking degree of the obtained crosslinked starch, and it may be easier to control the biodegradation rate of the produced anti-adhesion agent powder.

Next, carboxymethyl starch may be obtained using a second mixture including the cross-linked starch, carboxylic acid, basic compound, and catalyst. That is, hydrophilization (esterification reaction) may be performed using the second mixture. Specifically, carboxymethyl starch may be obtained through esterification of the cross-linked starch included in the second mixture, and substitution of the carboxymethyl group of the carboxymethyl starch through control of the esterification reaction. It may be to adjust the degree. In addition, it may be to control the anti-adhesion function of the anti-adhesion agent powder prepared by adjusting the degree of substitution of the carboxymethyl group of the carboxymethyl starch.

According to an exemplary embodiment of the present invention, the second mixture may include a second organic solvent. That is, the step of obtaining carboxymethyl starch; may be obtaining carboxymethyl starch using a second suspension containing the crosslinked starch, carboxylic acid, basic compound, catalyst, and second organic solvent. Specifically, the process of preparing a second suspension by adding the crosslinked starch, carboxylic acid, basic compound, and catalyst to the second organic solvent, reacting the second suspension, and then washing and drying with the second solvent is repeated. It may be to adjust the degree of substitution of the carboxymethyl group of the carboxymethyl starch obtained by doing.

According to an exemplary embodiment of the present invention, the second organic solvent may be alcohol having 1 to 3 carbon atoms, for example, ethanol, and may be the same as the first organic solvent. When using the second organic solvent of the above-mentioned type, dissolution and reaction of cross-linked starch, carboxylic acid, basic compound and catalyst may be facilitated, and cross-linked carboxymethyl starch may be easily obtained. In addition, since the second organic solvent can be recovered and reused as the first organic solvent, process efficiency can be increased.

According to an exemplary embodiment of the present invention, the carboxylic acid may be a carboxylic acid having 1 to 3 carbon atoms, and may be substituted with a halogen element such as Cl, Br or I. For example, it may be monochloroacetic acid (MCA). In the case of using the above-mentioned type of carboxylic acid, the reaction by the hydroxyl group of starch can be facilitated.

According to an exemplary embodiment of the present invention, the basic compound may include at least one of sodium hydroxide, calcium hydroxide, and lithium hydroxide, and may include, for example, sodium hydroxide. In the case of using the above-mentioned kind of basic compound, the esterification reaction of the cross-linked starch may be facilitated.

According to an exemplary embodiment of the present invention, the catalyst may include at least one of sodium tripolyphosphate (STTP), fumaric acid, maleic acid, succinic acid, adipic acid, diglycolic acid, and fumaryl chloride. In the case of using the above-mentioned kind of catalyst, the esterification reaction of the cross-linked starch can be facilitated.

According to an exemplary embodiment of the present invention, obtaining the cross-linked carboxymethyl starch; is obtained by adjusting the content, temperature and reaction time of the cross-linked starch, carboxylic acid, basic compound and catalyst included in the second mixture It may be to adjust the degree of substitution of the carboxymethyl group of carboxymethyl starch to be.

According to an exemplary embodiment of the present invention, the content of the crosslinked starch may be 10 parts by weight or more and 25 parts by weight or less based on 100 parts by weight of the second mixture. Specifically, the content of the crosslinked starch is 10 parts by weight or more and 20 parts by weight or less, 10 parts by weight or more and 15 parts by weight or less, 10 parts by weight or more and 25 parts by weight or less, 15 parts by weight or more based on 100 parts by weight of the second mixture. It may be 25 parts by weight or less, or 15 parts by weight or more and 20 parts by weight or less. When the crosslinked starch content in the above range is satisfied, it is easy to control the degree of substitution of the carboxymethyl group of the obtained carboxymethyl starch and the hydrophilicity of the anti-adhesion agent powder to be prepared, and the adhesion of the anti-adhesion agent powder to be prepared It may be easy to control the prevention function.

According to an exemplary embodiment of the present invention, the content of the carboxylic acid is 8 parts by weight or more and 15 parts by weight or less based on 100 parts by weight of the second mixture, and the content of the basic compound is 9 parts by weight based on 100 parts by weight of the second mixture. It may be 20 parts by weight or less. Specifically, the content of the carboxylic acid is 8 parts by weight or more and 14 parts by weight or less, 8 parts by weight or more and 13 parts by weight or less, 9 parts by weight or more and 15 parts by weight or less, 9 parts by weight or more 15 parts by weight based on 100 parts by weight of the second mixture. parts by weight or less or 10 parts by weight or more and 14 parts by weight or less, and the amount of the basic compound is 9 parts by weight or more and 18 parts by weight or less, 9 parts by weight or more and 16 parts by weight or less, 11 parts by weight based on 100 parts by weight of the second mixture. It may be 20 parts by weight or less, 13 parts by weight or more and 20 parts by weight or less, or 11 parts by weight or more and 18 parts by weight or less. When the contents of the carboxylic acid and the basic compound in the above range are satisfied, the degree of substitution of the carboxymethyl group of the obtained carboxymethyl starch and the hydrophilicity of the anti-adhesion agent powder can be easily controlled, and the prepared anti-adhesion agent powder can be applied to the subject. At the time of application, gelation strength and viscoelastic properties of the gel layer formed by gelation by moisture at the application site may be excellent.

According to an exemplary embodiment of the present invention, the content of the catalyst may be 0.1 parts by weight or more and 0.7 parts by weight or less based on 100 parts by weight of the second mixture. Specifically, the content of the crosslinked catalyst is 0.1 part by weight or more and 0.6 part by weight or less, 0.1 part by weight or more and 0.5 part by weight or less, 0.2 part by weight or more, 0.7 part by weight or less, 0.3 part by weight or more based on 100 parts by weight of the second mixture. It may be 0.7 parts by weight or less, or 0.2 parts by weight or more and 0.6 parts by weight or less. When the catalyst content in the above range is satisfied, the reaction efficiency of the second mixture can be improved, and the degree of substitution of the carboxymethyl group of the obtained carboxymethyl starch and the hydrophilicity of the anti-adhesion agent powder can be easily controlled. can

According to an exemplary embodiment of the present invention, obtaining carboxymethyl starch using a second mixture comprising the cross-linked starch, carboxylic acid, basic compound and catalyst; is the cross-linked starch, carboxylic acid, basic compound and mixing the catalyst to prepare a second mixture and performing a primary reaction by stirring at a temperature of 45 ° C. or more and 50 ° C. or less for 1 hour or more and 3 hours or less; and further adding a basic compound to the second mixture subjected to the first reaction and performing a second reaction at a temperature of 50° C. or more and 70° C. for 6 hours or more and 12 hours or less.

When the above-mentioned primary and secondary reaction conditions are satisfied, it may be easy to control the degree of substitution of the carboxymethyl group of the carboxymethyl starch obtained, and it is easier to control the anti-adhesion function of the anti-adhesion agent powder to be produced. can do.

According to an exemplary embodiment of the present invention, obtaining carboxymethyl starch using a second mixture comprising the cross-linked starch, carboxylic acid, basic compound and catalyst; is the cross-linked starch, carboxylic acid, basic compound and It may include; preparing a second mixture by mixing the catalyst and performing a primary reaction by stirring at a temperature of 45 ° C. or more and 50 ° C. or less for 1 hour or more and 3 hours or less. When the above-mentioned primary reaction conditions are satisfied, the hydroxyl group of the crosslinked starch reacts with a basic compound to sufficiently form a compound in the form of a salt, so that the reaction of the primary reacted second mixture with carboxylic acid is easy can be done

According to an exemplary embodiment of the present invention, obtaining carboxymethyl starch using a second mixture including the crosslinked starch, carboxylic acid, basic compound and catalyst; is a basic compound in the first reacted second mixture It may include; additionally adding and performing a secondary reaction at a temperature of 55 ° C. or more and 70 ° C. or less for 6 hours or more and 12 hours or less. Specifically, a basic compound is further added to the second mixture subjected to the first reaction, and at a temperature of 55 ° C. or more and 65 ° C. or 60 ° C. or more and 65 ° C. or less, 6 hours or more and 10 hours or less, 8 hours or more and 12 hours or less, or 8 It may be a secondary reaction for more than 10 hours and less than 10 hours. When the aforementioned secondary reaction conditions are satisfied, the degree of substitution of the carboxymethyl group may be improved while preventing a side reaction in which a glycolic acid type compound is formed.

Next, the particle size distribution of the carboxymethyl starch can be controlled. That is, it may be to adjust the particle size distribution of the anti-adhesion agent powder prepared by washing, drying, centrifuging and pulverizing the obtained carboxymethyl starch with a third organic solvent, and through the control of the particle size distribution, the anti-adhesion powder prepared It may be to control physical properties and anti-adhesion function.

According to an exemplary embodiment of the present invention, controlling the particle size distribution of the carboxymethyl starch; is the physical properties and It may be to control the anti-adhesion function.

According to an exemplary embodiment of the present invention, the third organic solvent may be alcohol having 1 to 3 carbon atoms, for example, ethanol, and may be the same as the first organic solvent and the second organic solvent. In the case of using the third organic solvent of the above-described type, it may be easy to control the particle size distribution of the anti-adhesion agent powder, and to easily control the physical properties and anti-adhesion function of the anti-adhesion agent powder. In addition, the third organic solvent can be recovered and reused as the first organic solvent and the second organic solvent, thereby increasing process efficiency.

According to an exemplary embodiment of the present invention, the drying may be performed by a spray drying method. When the drying is performed by the above-described method, it may be easy to control the particle size distribution of the anti-adhesion agent powder to be prepared, and to control the physical properties and anti-adhesion function of the anti-adhesion agent powder to be prepared.

Hereinafter, examples will be described in detail to explain the present invention in detail. However, embodiments according to the present invention can be modified in many different forms, and the scope of the present invention is not construed as being limited to the embodiments described below. The embodiments herein are provided to more completely explain the present invention to those skilled in the art.

Example: Preparation of anti-adhesion agent powder

Example 1

Potato starch (99%, potato starch) as starch and citric acid as a crosslinking agent were prepared. A first mixture was prepared by adding 100 mL of ethanol (95%, Sigma Aldrich) to the reactor, and adding 65 g of potato starch and 25 g of citric acid. At this time, the content of the citric acid was adjusted to 10 parts by weight or more and 25 parts by weight or less based on 100 parts by weight of the first mixture.

After stirring the first mixture at room temperature for 20 hours, the temperature was raised to 50 °C and dried until the moisture content of the first mixture reached 10%. Then, after additional drying at 120 ° C. for 5 hours, repeated washing and drying using ethanol to obtain a crosslinked starch.

Thereafter, monochloroacetic acid (MCA) as a carboxylic acid, sodium hydroxide (NaOH) as a basic compound, and sodium tripolyphosphate (STPP) as a catalyst were prepared. 100 mL of ethanol (95%, Sigma Aldrich) was added to the reactor, and 16 g of the cross-linked starch, 8 g of NaOH, 10 g of monochloroacetic acid, and 0.3 g of STPP were added to prepare a second mixture, and The temperature was raised and the first reaction was performed for 2 hours.

Thereafter, 8 g of NaOH was additionally added, the temperature was raised to 60 ° C, and the secondary reaction was performed for 8 hours, followed by repeated washing and spray drying using ethanol, and a classification process so that the average particle diameter (Dv50) was 50 μm or more and 100 An anti-adhesion agent powder having a size of ㎛ or less was obtained.

Comparative Example 1

An anti-adhesion agent powder was prepared in the same manner as in Example 1, except that the particle size distribution of the carboxymethyl starch was not controlled.

Comparative Example 2

An anti-adhesion agent powder was prepared in the same manner as in Example 1, except that the first mixture was prepared without adding a crosslinking agent.

Preparation Example: Preparation of anti-adhesion gel layer

Preparation Example 1

The anti-adhesion agent powder according to Example 1 was mixed with distilled water to form an anti-adhesion gel layer. At this time, the content of the anti-adhesion agent powder was adjusted to be 5 parts by weight based on 100 parts by weight of the distilled water.

Preparation Example 2

An anti-adhesion gel layer was prepared in the same manner as in Preparation Example 1, except that the content of the anti-adhesion agent powder was adjusted to 7.5 parts by weight based on 100 parts by weight of the distilled water.

Experimental example

Appearance evaluation

Images of the anti-adhesion powder according to Example 1 are shown in FIGS. 2 and 3 below.

Specifically, Figure 2 is an optical microscope (DZ3, Union) image showing the properties of the anti-adhesion agent powder according to Example 1, Figure 3 is an FE-SEM (S-SEM) showing the microstructure of the anti-adhesion agent powder according to Example 1 4300, HITACHI) image.

Referring to FIGS. 2 and 3, the anti-adhesion agent powder according to Example 1 is formulated in a powder form and can be sprayed onto a wound requiring anti-adhesion by a spraying device, and can be accurately applied to the wound even during laparoscopic and minimally invasive procedures. It can be confirmed that spraying is possible. In addition, it can be confirmed that the particle size distribution is controlled to have uniform powder particles. Through this, it can be seen that it is easy to adjust physical properties such as gelation strength and viscoelasticity of the anti-adhesion gel layer formed according to the control of the spray amount of the anti-adhesion agent powder.

Viscosity measurement and crosslinking evaluation

Viscosity was measured using a rotational viscometer (RM200 TOUCH CP400 or RM200 TOUCH, LAMYRHEOLOGY Co.) under conditions of 25±1° C., LV-1 type spindle, and 60 rpm.

Then, the viscosity of potato starch and crosslinked starch as uncrosslinked starch was measured, and the degree of crosslinking was calculated by Equation 1, and shown in Table 1 below.

Degree of substitution evaluation

2 g of a sample of the anti-adhesion agent powder according to Example 1 and 100 cm ³ of a 2% NaCl solution were prepared and dispersed by stirring. After 15 minutes, titration was performed with 1M NaOH using an automatic titrator (636 Metrohm, Herisau, Switzerland) at room temperature. At this time, the titration was performed at pH 12 and the end point was calculated by the instrument as the inflection point of the pH curve for the titrated amount of NaOH. The above titration was repeated three times for each sample and the average value of the equivalent volume was calculated for calculation of the degree of substitution.

Then, the degree of substitution of the carboxymethyl group of the anti-adhesion agent powder according to Example 1 was calculated by Equation 2 and Equation 3, and shown in Table 1 below.

division Degree of crosslinking (%) Degree of substitution (%) Example 1 22 81

Referring to Table 1, the anti-adhesion agent powder according to the present invention can control the crosslinking degree of the cross-linked starch through the control of the etherification reaction, and the carboxymethyl group of the anti-adhesion agent powder through the control of the esterification reaction. It can be confirmed that the degree of substitution of can be adjusted. That is, it can be seen that by adjusting the degree of substitution of the carboxymethyl group, the hydrophilicity of the prepared anti-adhesion agent powder can be adjusted.

Particle size analysis evaluation

The average particle diameter (Dv50) of the particles was measured using a laser diffraction scattering type particle size analyzer (Particle Size Analyzer, PSA). Specifically, D100, D90, D50, and D10 were measured using the laser diffraction scattering particle size analyzer, and a cumulative volume-based median diameter (Dv50) was calculated from the particle size distribution map, and this was taken as the average diameter.

Thereafter, the particle size distribution of the anti-adhesion agent powder before/after the particle size distribution control was measured and shown in FIGS. 4 and 5, respectively.

4 and 5 are images showing the particle size distribution of the anti-adhesion powder according to Comparative Example 1 and Example 1. Specifically, FIG. 4 is an image showing the particle size distribution of the anti-adhesion agent powder before particle size distribution control (Comparative Example 1), and FIG. 5 is an image showing the particle size distribution of the anti-adhesion agent powder after particle size distribution control (Example 1).

Referring to Figures 4 and 5, it can be seen that the anti-adhesion agent powder according to Example 1 has uniform powder particles by controlling the particle size distribution. Through this, it can be seen that it is easy to adjust physical properties such as gelation strength and viscoelastic properties of the anti-adhesion gel layer formed according to the control of the spray amount of the anti-adhesion agent powder.

Storage modulus evaluation

The storage modulus was measured using an ARES Fluid Rheometer (Rheometrics) at 25° C. through a dynamic oscillation test.

In order to confirm the structural strength according to the anti-adhesion powder content of the anti-adhesion gel layer, the gel storage modulus of the anti-adhesion gel layer according to Preparation Examples 1 and 2 was evaluated and shown in FIG. 6 .

Figure 6 is an image showing the storage modulus (storage modulus) evaluation results of the anti-adhesion gel layer according to Preparation Example 1 and Preparation Example 2.

Referring to FIG. 6, it was confirmed that the anti-adhesion gel layer according to Preparation Example 2 had about 10 ³ times more strength than the anti-adhesion gel layer according to Preparation Example 1. On the other hand, it was confirmed that the application of excessive powder rather weakened the strength of the gel layer. That is, it was confirmed that the gelation rate and the strength of the gel increased when the content of the powder was increased with respect to the water content. Specifically, the higher the storage modulus value representing the gel properties, the more solid gel formation is, and the gel storage modulus value increases more than 10 ³ times as the powder content increases (5%, G' = 1.04 Pa, 7.5%, G' = 3033.9 Pa). Through this, it can be seen that the anti-adhesion agent powder according to the present invention can implement a better anti-adhesion function by adjusting the content of the powder relative to moisture within a certain range, so that it is easy to control physical properties such as gelation strength and viscoelastic properties.

Viscoelastic evaluation

Viscoelasticity was measured for dynamic viscoelasticity using an ARES measuring instrument (Rheometric Scientific) using a temperature dispersion measurement method by a sinusoidal wave vibration method in the range of oscillation frequency of 5 to 10 rad/s.

In order to confirm the change in physical properties according to the anti-adhesion powder content of the anti-adhesion gel layer, the viscoelasticity of the anti-adhesion gel layer according to Preparation Examples 1 and 2 was evaluated and shown in FIG. 7 .

7 is an image showing the evaluation results of the viscoelasticity of the anti-adhesion gel layer according to Preparation Example 1 and Preparation Example 2.

Referring to FIG. 7, it was confirmed that the anti-adhesion gel layer according to Preparation Example 2 had a stronger structure than the anti-adhesion gel layer according to Preparation Example 1, and thus had excellent structural stability of the gel layer against external strain. In addition, it was confirmed that the linear viscosity region according to Example 1 clearly appeared, and a constant storage modulus value was maintained over time. Through this, the anti-adhesion agent powder according to the present invention can easily control the gelation rate and viscoelastic properties by adjusting the content of the anti-adhesion agent powder for moisture, and has excellent gelation strength and viscoelastic properties, so that it is an anti-adhesion film in the form of a film or membrane. It can be seen that a similar level of anti-adhesion function can be implemented.

Decomposition rate evaluation

The decomposition rate of the anti-adhesion agent powder according to Example 1 was evaluated by the following method.

Amylase and proteinase were added to PBS at a weight ratio of 1:1 and mixed to prepare an enzyme solution having a concentration of 1 unit/ml. The anti-adhesion agent powder according to Example 1 and Comparative Example 2 was added to and dispersed in the enzyme solution, and maintained at 37 °C. Then, the decomposition rate of the anti-adhesion agent powder was evaluated by measuring the change in absorbance of light over time using a UV-Vis spectrometer (Lambda 265, PerkinElmer).

Specifically, the anti-adhesion agent powder according to Example 1 using the change in absorbance over time of the enzyme solution to which each anti-adhesion agent powder was added and the average decomposition period in the body of the anti-adhesion agent powder according to Comparative Example 2 without crosslinking The time required for degradation in the body was estimated.

Thereafter, the measured absorbance and the calculated duration of degradation in the body for the enzyme solution to which each anti-adhesion powder was added are shown in Table 2 below.

In addition, one week after the addition of the anti-adhesion agent powder, the concentration of the anti-adhesion agent powder remaining in each enzyme solution was visually evaluated by the degree of Tyndall phenomenon through a laser, and the results are shown in FIG. 8 below.

division absorbance Decomposition period (days) Early 1 day later 1 week later Example 1 1.0000 0.9011 0.77895 21 to 32 days Comparative Example 2 1.0000 0.7653 0.47473 15 to 20 days

8 is an image showing the difference in concentration change after a certain period of time in the enzyme solution of the anti-adhesion agent powder according to Example 1 and Comparative Example 2. Specifically, Figure 8 (a) is an image showing the concentration change of the anti-adhesion agent powder according to Example 1, Figure 8 (b) is an image showing the concentration change of the anti-adhesion agent powder according to Comparative Example 2.

Referring to Figure 8, after 1 week in the enzyme solution, the concentration of the anti-adhesion agent powder (a) according to Example 1 and the anti-adhesion agent powder (b) according to Comparative Example 2 was visually evaluated by the degree of Tyndall phenomenon As a result, in the case of the anti-adhesion powder according to Example 1, it was confirmed that a relatively high concentration of anti-adhesion agent powder particles existed in the enzyme solution. Through this, since the anti-adhesion agent powder according to Example 1 includes cross-linked starch and carboxymethyl starch prepared therefrom, the time required for decomposition is increased compared to the anti-adhesion agent powder according to Comparative Example 2 without cross-linking. can know that

Referring to Table 2, as a result of the evaluation of the decomposition rate using a UV-Vis Spectrometer, the absorbance measured for the enzyme solution (a) to which the anti-adhesion powder according to Example 1 was added was the enzyme to which the anti-adhesion powder according to Comparative Example 2 was added. It was confirmed that it corresponds to 1.4 to 1.6 times the absorbance measured for solution (b). Therefore, as an anti-adhesion agent powder that has not undergone a crosslinking step, the anti-adhesion agent powder according to Comparative Example 2 has an average decomposition period in the body of 15 to 20 days, so the anti-adhesion agent powder according to Example 1 has an in-body decomposition period of 21 to 32 days counted as days Through this, since the anti-adhesion agent powder according to Example 1 includes cross-linked starch and carboxymethyl starch prepared therefrom, the decomposition period is increased compared to the anti-adhesion agent powder according to Comparative Example 2 without cross-linking, It can be seen that the degradation rate decreases.

Therefore, the method for producing the anti-adhesion powder according to the present invention adjusts the decomposition rate of the anti-adhesion agent powder in the body by controlling the degree of crosslinking of carboxymethyl starch contained in the anti-adhesion agent powder, so that the period required for tissue wound healing after surgery It can be seen that sufficient anti-adhesion function can be implemented while

The foregoing detailed description is intended to illustrate and explain the present invention. In addition, the foregoing merely represents and describes preferred embodiments of the present invention, and as described above, the present invention can be used in various other combinations, modifications, and environments, and the scope of the inventive concept disclosed herein, the foregoing Changes or modifications are possible within the scope equivalent to the disclosure and / or within the scope of skill or knowledge in the art. Accordingly, the above detailed description of the invention is not intended to limit the invention to the disclosed embodiments. Also, the appended claims should be construed to cover other embodiments as well.

Claims (10)

It contains CarboxyMethyl Starch (CMS), which uses cross-linked Starch powder as a raw material,
Anti-adhesion agent powder having a degree of cross-linking calculated by Equation 1 below of the cross-linked starch of 15% or more and 22% or less:
[Equation 1]
Degree of crosslinking (%) = {(V _A - V _B ) / V _A } X 100
In Equation 1, V _A is the viscosity (cp) of uncrosslinked starch, and V _B is the viscosity (cp) of crosslinked starch. According to claim 1,
Anti-adhesion powder having a degree of substitution of the Carboxymethyl Group calculated by Equation 2 below: 0.6 or more and 0.8 or less:
[Equation 2]
Degree of substitution = (162 X n _COOH ) / {m _dry - (58 X n _COOH )}
In Equation 2, 162 is the molecular weight (g/mol) of anhydrous glucose unit (AGU), n _COOH is the amount of COOH (mol) determined by back titration, and m _dry is the mass (g) of the dried powder sample. , and 58 is the mass increase (g/mol) of the anhydrous glucose unit according to the increase of the carboxymethyl group. According to claim 1,
further comprising a crosslinking agent;
The anti-adhesion agent powder comprising at least one of epichlorohydrin, citric acid and citrus oil. According to claim 1,
The anti-adhesion agent powder having an average particle diameter (Dv50) of 50 μm or more and 100 μm or less. According to claim 1,
When the anti-adhesion agent powder is applied to an object, it is gelled by moisture at the application site to form a gel layer having a storage modulus of 10 ³ Pa or more. According to claim 5,
The anti-adhesion powder is applied to the object in an amount of 5 parts by weight or more and 10 parts by weight or less based on 100 parts by weight of the moisture of the application site. Obtaining cross-linked starch using a first mixture comprising starch and a cross-linking agent;
Obtaining carboxymethyl starch using a second mixture comprising the cross-linked starch, carboxylic acid, basic compound and catalyst; and
Controlling the particle size distribution of the carboxymethyl starch; method of producing an anti-adhesion powder comprising a. According to claim 7,
The content of the starch is 50 parts by weight or more and 70 parts by weight or less based on 100 parts by weight of the first mixture,
The content of the crosslinking agent is 10 parts by weight or more and 25 parts by weight or less based on 100 parts by weight of the first mixture. According to claim 7,
Obtaining the cross-linked starch;
Obtaining a dried first mixture by stirring the first mixture at room temperature for 18 hours or more and 22 hours or less and drying at a temperature of 40 ° C. or more and 60 ° C. or less; and
Obtaining the cross-linked starch by reacting the dried first mixture at a temperature of 110 ° C. or more and 130 ° C. or less for 5 hours or more and 7 hours or less;
The moisture content of the dried first mixture is based on 100 parts by weight of the dried first mixture, 10 parts by weight or more and 15 parts by weight or less. According to claim 9,
The content of the carboxylic acid is 8 parts by weight or more and 15 parts by weight or less based on 100 parts by weight of the second mixture,
The content of the basic compound is 9 parts by weight or more and 20 parts by weight or less based on 100 parts by weight of the second mixture.

Images