KR101442479B1 - Collagen based biological gelatin glue - Google Patents

Abstract

The present invention relates to a gelatin biobinding agent applying isinglass based on collagen, a method to manufacture the biobinding agent, and a constant temperature injector to inject the biobinindng agent. To achieve the purpose, provided in the present invention are a biobiniding agent including collagen, isinglass, and water. The biobinding agent in accordance to the present invention is suitable for a living body, has excellent adhesion, and can even be adhered under humid environment and higher temperature than a body temperature for a long time.

Description

Collagen-based biological gelatin glue < RTI ID = 0.0 >

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bioabsorbable adhesive, and more particularly to a gelatine bioabsorbent to which a bean curd is applied based on collagen. The present invention also relates to a method for producing the adhesive for a living body and a thermostat for injecting the adhesive for a living body.

There are three products that are commercially available and sold as medical adhesives worldwide: cyanoacrylate glue, fibrin glue, and protein gelatin glue.

The cyanoacrylic glue is used for less than about 5% for medical use, and the initial product (methyl and ethyl cyanoacrylate) is not used due to the serious toxicity of tissue, and octyl cyanoacrylate (Dermabond) It is an adhesive that is approved and sold by the US FDA. Cyanoacrylic glue is known as one of the most adhesive among the three adhesives. However, there is a disadvantage in that there is a problem in biocompatibility due to the production of by-products, and a high production and selling unit price.

Fibrin glue acts as a hemostatic agent and is used as a bioadhesive agent because of its tissue adhesion. Tisseel in 1998, and Beriplast-P in 2003. It has been approved by the US FDA and is used with collagen adhesives as a hemostatic and tissue adhesive. However, the adhesive strength is weak, the adhesive holding force is weak in the water environment, and there is a problem of immunity. In addition, there is a disadvantage that the production cost of the product is high.

Protein (gelatin) glue is a natural water-soluble protein bioadhesive extracted from collagen which is the base material of the adhesive. It is used for drug delivery or edible use, and is characterized by microbial degradation. Due to low antibody reaction, it is spotted as a biocompatible adhesive, but its adhesive strength is weak and weak to moisture.

It is anticipated that a new bioadhesive agent capable of replacing the two adhesives listed above is expected to be possible if it is possible to increase the initial bonding strength or increase the adhesive holding strength under water conditions by adding a biocompatible natural material to the collagen-based gelatin glue .

The use of suture in the operation of ophthalmic patients has been reported to cause complications such as foreign body reaction, hypersensitivity reaction, and granuloma formation by the suture itself. In the case of retinal perforation, which is a serious complication during suturing, 1% of cases are reported. To solve these inflammatory reactions and complications, it is necessary to develop a tissue adhesive to replace the use of a suture, and studies for this have been actively conducted.

Cyanoacrylate, and skin glue. However, it has been reported that the initial adhesive force is very weak and muscle dislocation is not suitable for ophthalmic surgery, and the manufacturing and selling unit costs are high.

Collagen-based gelatin adhesives have safety and biocompatibility that can be used as biocompatible adhesives, but they are difficult to use as medical tissue adhesives because of their low instantaneous adhesion and short duration. In addition, since the affected part is higher than the normal body temperature and the humid environment caused by the body fluids generated in the affected part makes it difficult to maintain the adhesion, it is necessary to increase the adhesion of the collagen adhesive and to develop an adhesive capable of maintaining adhesion in an environment such as the affected part Do.

1. Japanese Patent Application Laid-Open No. 1998-314294

2. Korean Patent Registration No. 1093391

An object of the present invention is to provide a bioabsorbable adhesive that is suitable for a living body, has excellent adhesive force, and can be adhered for a long time even in a humid environment higher than body temperature.

Another object of the present invention is to provide a method for producing the adhesive for living body.

It is still another object of the present invention to provide a thermostat for injecting the adhesive for a living body.

In order to attain the above object, the present invention provides an adhesive for living body comprising collagen, water repellent and water.

In the adhesive according to the present invention, the mixing ratio of collagen: beater: water is preferably 2: 0.5 to 2.5: 0.5 to 1.5 in weight ratio.

It is preferable that the adhesive according to the present invention maintains adhesion for 5 minutes or more with respect to a load of 100 g after bonding the adhesive, and the tensile strength of the adhesive is preferably 5 N or more.

The adhesive according to the present invention can be reversibly changed in gel state and sol state based on 40 ± 5 ° C.

The adhesive according to the present invention can be usefully used as a tissue adhesive or a hemostatic agent.

In addition, the present invention relates to a method for preparing a pharmaceutical composition, which comprises the steps of mixing and heating collagen, butterfly, and water to form a sol mixture; And cooling the mixture to form a gel-state adhesive.

In the production process according to the present invention, the heating temperature may be 40 to 100 ° C.

In the manufacturing method according to the present invention, the adhesive may be formed in the form of a film or a capsule. The capsule may be formed by wrapping a mixture of a sol or gel adhesive in a film and then sealing the film. Film.

The method of manufacturing an adhesive according to the present invention may further include a step of vacuum packing and then storing at low temperature or freezing.

The present invention also relates to a method for producing a bioabsorbable bioabsorbable bioabsorbable polymer, Applying an adhesive in a sol state to the adherend; And a step of cooling the coated adhesive to convert it into a gel state.

In the bonding method according to the present invention, a film or a capsule type adhesive may be used, and the heating temperature may be 40 to 100 캜.

In the bonding method according to the present invention, the adhesive can be heated and applied using a thermostatic injector.

The present invention also relates to a substrate; And an adhesive layer formed on the base material and comprising an adhesive layer containing collagen, butterfly, and water.

In the adhesive film according to the present invention, the substrate may be a release paper.

The present invention also relates to a core comprising collagen, water repellent and water; And a shell formed on the outside of the core.

In the adhesive capsule according to the present invention, the core may be in a sol state or a gel state, and the shell may be an adhesive film containing collagen.

The present invention also relates to an injection device for injecting an adhesive containing collagen, boehmite and water into a living body; And a heating means for heating the injection means.

In the thermostat injector according to the present invention, the injection means may be a syringe, and the syringe may be installed in a thermostatic injector in a replaceable manner.

In the thermostat injector according to the present invention, the heating means may be a hot wire element, the hot wire element may be embedded in a silicon material, the current applied to the hot wire element may be 40 to 100 mA, and the voltage may be 40 to 100 V.

The adhesive for a living body according to the present invention is suitable for a living body and has excellent adhesive force, and can be adhered for a long time even in a humid environment higher than body temperature.

1 is a cross-sectional view showing an example of a thermostat injector usable in the present invention.
Fig. 2 schematically shows an experiment for measuring the adhesive force (tensile strength).
3 is a graph showing the tensile strength of Example 1. Fig.
4 is a graph showing the tensile strength of Comparative Example 1. Fig.
5 is a graph showing the tensile strength of Comparative Example 2. Fig.
6 is a graph showing the tensile strength of Comparative Example 4. Fig.

Hereinafter, the present invention will be described in detail.

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bioabsorbable adhesive, and more particularly to a gelatine bioabsorbent to which a bean curd is applied based on collagen. The present invention also relates to a method for producing the adhesive for a living body and a thermostat for injecting the adhesive for a living body.

glue

The adhesive according to the present invention can be made up of collagen, boehmite and water.

Collagen is a light protein that is mainly found in animal bones and skin, and is distributed in cartilage, organ membranes, hair, etc. It is also a component of fish scales. Also known as collagen, it exists as a fibrous solid. The electron microscope shows a complex horizontal pattern structure. It does not dissolve in water, dilute acid, or dilute alkali, but when boiled, it becomes gelatin and dissolves.

An isinglass is an adhesive made from a bladder that is an air pocket of a fish. Buresaro can use bures such as croaker, sturgeon, and cod. It is a glue that is made by boiling the water in the water, then cutting it off the fish 's breeze, washing it well with water, and sticking it to the glue.

Water is a major constituent of the bioadhesive according to the present invention and can not be applied as an adhesive since it does not change into a sol state when composed of only collagen and butterfly without water. Water is preferably purified water such as deionized water.

In addition to the combination of collagen, butterfly, and water, various combinations of the ingredients such as arabic gum solution, masking solution for painting, ragweed solution, titanium dioxide powder, mussel adhesive material extract, agar, and rosin were tested in combination. In conclusion, the desired adhesive strength was obtained only when collagen, boehmite, and water were combined.

The weight ratio of collagen: beater: water is preferably 2: 0.5 to 2.5: 0.5 to 1.5, more preferably 2: 1: 1. If the content of buleflo is too low on the basis of collagen, the adhesive force may be lowered, and if the content of buleflo is too large, the viscosity may be lowered and the adhesive strength may be lowered. When the content of water is too low based on collagen, it may not be converted into a sol state. If the content of water is too high, the viscosity may be lowered and the adhesive strength may be lowered.

The adhesive according to the present invention is capable of reversible change in gel state and sol state based on 40 ± 5 ° C. Specifically, the adhesive according to the present invention is in a gel state at room temperature. When heated to about 40 ° C or more, it is in a sol state. When it is cooled to less than 40 ° C, it is in a gel state again. do.

The adhesive according to the present invention is excellent in adhesion. Specifically, an initial adhesive force of 100 g or more is required due to the elasticity of muscles and a force applied on the procedure. Adhesion can be maintained for 5 minutes or more with respect to a load of 100 g after bonding of the adhesive according to the present invention. The upper limit of the adhesive holding time can be, for example, 10 years or permanent. In addition, the tensile strength of the adhesive according to the present invention is as high as 5 N or more. The upper limit of the tensile strength may be 20 N, for example.

On the other hand, the moisture and temperature affect the adhesive force of the adhesive. Specifically, the adhesive force is lowered under the condition of moisture such as living body and / or the temperature condition of body temperature or more. However, the adhesive according to the present invention can exert an excellent initial adhesion even under the conditions of water and body temperature.

The adhesive according to the present invention can be usefully used as a tissue adhesive or a hemostatic agent.

Adhesive Manufacturing Method

A method for producing a bioabsorbable adhesive according to the present invention comprises the steps of mixing and heating collagen, butterfly, and water to form a sol mixture; And cooling the mixture to form a gel-state adhesive.

The order of mixing is not particularly limited, for example, after mixing collagen and water first, then the beater can be mixed later. The heating time is also not particularly limited, and for example, it may be heated from the beginning to the end or partially heated at least once. According to one embodiment of the present invention, it is possible to prepare a mixed solution in a sol state by first mixing collagen and water, heating the mixture, and mixing the bean sprouts.

The heating method is not particularly limited, and for example, the mixture can be heated directly, or indirectly heated using a water bath method. The heating temperature is not particularly limited as long as it is 40 DEG C or higher, but when heated at a high temperature (60 to 80 DEG C), the time required to make the sol is shortened and a uniform mixture can be obtained. The upper limit of the heating temperature may be, for example, 100 캜.

The cooling method is not particularly limited, and can be naturally cooled, for example, at room temperature (20 ± 10 ° C), or cooled using cooling water or ice water.

In the method for producing an adhesive according to the present invention, the adhesive may be produced in the form of a film or a capsule.

The method of manufacturing an adhesive according to the present invention may further include a step of vacuum packing and then storing at low temperature or freezing. Since the constituent components of the bioadhesive according to the present invention are made of natural materials, they are easily decomposed by strains such as molds (Asperigilus spp. And Cladosporium spp.) That always float in the air. In order to prevent corruption, it is better to vacuum-pack as soon as possible after making the adhesive. It is desirable to store the adhesive at low temperature after vacuum packing. The storage temperature is preferably 10 占 폚 or less, and preferably 4 占 폚 or less. Prior to vacuum packaging, the adhesive can be cut to a certain size as needed.

Adhesive film

The adhesive film for a living body according to the present invention may comprise a substrate and an adhesive layer formed on the substrate and containing collagen, water repellent and water.

As the substrate, release paper made of paper, plastic, or the like can be used. The thickness of the substrate is not particularly limited and may be suitably adjusted as necessary.

The adhesive layer is a film-like layer containing collagen, water repellent and water. The thickness of the adhesive layer is not particularly limited and can be suitably adjusted as necessary.

The adhesive film can be obtained by thinly applying a sol mixture in the form of a film on a substrate such as a release paper and then cooling it.

Adhesive Capsule

The adhesive capsule for a living body according to the present invention may comprise a core containing collagen, water repellent and water, and a shell formed on the outside of the core.

The shape of the capsule is not particularly limited and may be, for example, cylindrical, spherical, polygonal, or the like. The size of the capsule is not particularly limited, and can be appropriately adjusted as needed.

The core may consist of a sol or gel adhesive composition containing collagen, beater and water according to the present invention.

The shell may be formed over the entire outer surface of the core and may also be partially formed. The outer wrapping shell may be made of an adhesive film, which may be made of the same or similar composition as the inner core, for example an adhesive film containing collagen.

The adhesive capsules can be obtained by wrapping the core with a pre-made adhesive film (shell) with the adhesive mixture of the sol state or the gel state as the core, and sealing the inner mixture so as not to come out. Sealing can be done through warming, which requires warming to very low temperatures so that the internal mixture does not change to a sol state at the time of warming.

Adhesive bonding method

The method for adhering a bio-adhesive according to the present invention comprises the steps of: heating a gel-like bio-adhesive comprising collagen, boehmite and water to a sol state; Applying an adhesive in a sol state to the adherend; And cooling the applied adhesive to convert to a gel state.

The adhesive can be adhered in the form of a film or a capsule. When the adhesive is adhered in the form of a disposable capsule, it is possible to solve the disadvantage of mixing and manufacturing the adhesive for each procedure and sticking the adhesive mixture on the outer wall of the syringe.

In the bonding method, heating can be referred to as warming. The warming method is not particularly limited. For example, the gel-like adhesive may be heated directly or indirectly by using water or the like. Specifically, it is possible to use a water bath or immerse in water at 40 DEG C or higher for a certain period of time, for example, for 10 to 15 seconds.

The warming temperature is not particularly limited as long as it is 40 DEG C or higher, but the warming temperature may affect the adhesion force. For example, when warming at 60 占 폚, the adhesive melts more effectively, becomes more uniform sol state, and has excellent adhesion as compared to warming at 43 占 폚. That is, the higher the temperature, the greater the solubility, uniformity and adhesion of the adhesive. However, if the temperature is too high, it is difficult to apply directly to living bodies, and therefore, it is preferable to perform warming at 80 DEG C or lower, preferably 70 DEG C or lower. The optimal warming temperature may be 40 to 60 占 폚.

The application method is not particularly limited, and for example, a syringe or the like can be used, and a specially prepared constant temperature injector can be used. The thermoinjector will be described in detail later. The coating temperature is preferably 40 DEG C or lower, and more preferably, it is preferable to apply the adhesive at room temperature to obtain excellent adhesion.

The cooling method is not particularly limited, and can be naturally cooled, for example, at room temperature (20 ± 10 ° C), or cooled using cooling water or ice water. Excellent adhesion can be obtained through cooling. It is considered that the phenomenon of shrinkage upon cooling affects the adhesion to the surface.

Thermostat injector

The adhesive according to the present invention can be adhered using a thermostat injector. The thermostat injector can simultaneously heat and apply the adhesive.

The thermostatic injector may include injection means and heating means. FIG. 1 is a cross-sectional view showing an example of a constant temperature injector usable in the present invention. The constant temperature injector according to an embodiment of the present invention may include a body 10, an injection means 20 and a heating means 30 . In addition, a temperature sensor may be provided for checking the heating temperature. 1 shows an example of the thermostat injector, and the structure of the thermostat injector is not limited to that shown in Fig. 1, but can be changed into various structures.

The body 10 may be made of plastic, metal, ceramic, or the like. The body 10 may be integrally formed, or may be manufactured in an assembled form in which two or more separate bodies are separately manufactured and assembled.

As the injection means 20, a syringe may be used. The injection volume can be adjusted through the syringe. For example, when an overdose is injected, the amount of injection can be adjusted by inversely. Screws can be connected to the syringe for fine adjustment of injection volume. The syringe may be made of plastic or glass. The syringe includes openings such as inlet and outlet, and the heat loss through the open area is not as good as the experimental results. The syringe can be installed in a form that can be replaced with an injector. In this case, the syringe is advantageous in that it is hygienic and simple in structure and easy to use.

As the heating means 30, a hot wire element can be used. Although a peltier element can be used, it is not preferable because of a problem of stability. The heat ray element is a device using resistance heat caused by the resistance when the electric current is applied to the wire. It is light and durable, easy to manufacture, convenient in temperature control, more advantageous than Peltier element in terms of production cost and stability in use.

The hot wire element can be coated with a flexible material such as silicone rubber, i.e., a silicone rubber heater with built-in heat wire. When silicone rubber material is applied, there is an advantage that it can be applied to a desired shape. BNC connectors can be installed to connect the hot wire device to the power source.

The hot wire element can be installed inside or outside the injector. 1 shows a case where a hot wire element is installed inside an injector. For example, in the form of direct wrapping onto an injection means such as a syringe. In this case, it is possible to install the heat ray element in the form of wrapping the heat ray element one or more times in the injection means, but the heating temperature may increase as the number of times of wrapping increases.

When the hot wire element is installed inside the injector, the size and thickness of the injector may be increased. Therefore, unlike FIG. 1, a hot wire element may be provided outside the injector. In this case, a groove can be formed outside the injector body so that the heat ray element does not slip.

The current applied to the hot wire element is preferably 40 mA or more, and the voltage is preferably 40 V or more. If the current and voltage are too low, the heating temperature may be low and the warming may become difficult. Conversely, if the current and voltage are too high, the heating temperature may be high and the warming may become difficult. The upper limit of the current and the voltage may be, for example, 100 mA and 100 V, respectively.

The present invention provides a bioadhesive agent capable of adhering skin tissue using a natural animal material which is free from inflammation and can be directly used in a living body.

In the present invention, the adhesion of collagen-based gelatin adhesive was improved by increasing the adhesive strength, and the adhesive strength was increased as compared with the conventional collagen adhesive, and it was confirmed that the adhesiveness was maintained for a long time under a humid environment or at a temperature of 40 ° C. It is a traditional glue that is used to make bows, and it can be used as a biocompatible adhesive since it uses natural animal materials. The optimum ratio of collagen: butterfly: water = 2: 1: 1 was higher than that of conventional gelatin adhesive, and it was possible to bond for a long time under humid environment. The adhesive of the present invention was applied to the eye muscles of the rabbit to confirm adhesion properties and biocompatibility. It is difficult to use the adhesive as a substitute for a medical suture during ocular surgery. However, it is difficult to use an adhesive for emergency hemostasis of a skin trauma and other dental functional adhesives As shown in Fig.

The gelatine synthetic gelatine adhesive according to the present invention has an advantage in that it has an initial adhesive strength higher than that of a commercialized gelatine adhesive and has a longer adhesive holding time even in a water condition so that the adhesive property is improved as compared with a conventional product. It is a traditional Korean glue that is used to make a prototype of a bow, and it can be used as a natural animal adhesive material having excellent adhesive property when it is made into glue form by mixing with water after drying the ball of the fish. However, when the sole solution alone was used, the viscosity was low and the viscosity could be increased by mixing it with the gelatin adhesive, and the adhesive strength of the gelatin adhesive could be increased by mixing the soap solution. The adhesiveness of the eye muscle tissue was directly applied to the rabbit eye muscles of the present invention. As a result, the initial adhesion was excellent and the eye muscles were successfully adhered during the procedure. At 48 hours after the procedure, it was confirmed that there was no inflammatory reaction. It was confirmed that the initial adhesive strength was excellent when applied to the affected area, and it was confirmed that it could be used as a tissue adhesive or a hemostatic agent for emergency treatment because there was no inflammation reaction.

The bevelpole synthetic gelatin adhesive according to the present invention can be mass-produced, and the production cost of the product can be reduced, thereby making it possible to produce an inexpensive bioadhesive or hemostatic agent. Especially, it is a new adhesive that can replace some of the applications of conventional adhesive products because it can be used as an emergency trauma treatment and hemostatic agent and has no inflammation reaction. It is a new adhesive which can be used in industrial fields related to dental high functional adhesives We expect that it will be able to apply and apply the function. Considering the size of the suture market and the sales trend of tissue adhesives, the market value of the adhesive product of the present invention is expected to be higher than that of conventional tissue adhesive products, and a high market share due to commercialization It is expected.

[Example 1]

1. Adhesive Manufacturing

The dried beak was soaked in water at 80 DEG C for 1 hour to prepare a bean curd solution. Water was deionized water. Collagen, butterfly, and water were mixed and heated at a weight ratio of 2: 1: 1. When the temperature of the hot plate was fixed at 75 ℃, the water bath was started and the mixture was changed into the form of the sol. The sol mixture was applied to a pile and cooled to room temperature to form a film. For the convenience of the adhesive strength test, the gelatin adhesive was cut to a suitable size in the form of a film. The gelatin adhesive was vacuum packed in order to prevent the decay of the gelatin adhesive and then stored in a cold state at a low temperature.

2. Adhesion Experiment

After the adhesive was warmed at a temperature of 60 캜, the adhesion test was carried out. Adhesion time wrapped with aluminum foil was measured by connecting a weight of 100 g load while maintaining constant temperature (40 ° C) using a dryer. The adhesive was applied between the wood and the fingers, and then the adhesive was applied for 3 minutes under pressure. As a result, the adhesive strength was sustained for 5 minutes or more and 100 g. In addition, after applying the adhesive between the wood and the wood, it was adhered by applying pressure for 3 minutes, and after confirming the adhesion, it sustained a load of 100 g over 5 minutes.

In addition, the adhesive strength (tensile strength) test was conducted with Fig. Specifically, the adhesive thus prepared was injected onto a small-sized tree and adhered at room temperature for 1 minute to carry out an adhesion test. The tensile strength test equipment used in the general physics experiment was used for the adhesion test and the wire was connected to the wood for easy holding of the pulling part and support part. As a result of the test, as shown in FIG. 3, a tensile strength of about 8.5 N was obtained.

3. Animal experiments

Animal experiments were conducted to investigate bioadhesive power. Animal experiments were performed on eye muscles of rabbit (rabbit) eye muscles, sclera, and conjunctiva. The adhesive was warmed at a temperature of 60 DEG C and then applied to a sclera or the like using an injector. Animal experiments showed that muscle adhesion lasted for about 3 minutes and the conjunctiva was well attached. It was confirmed that the adhesive strength was higher than that of conventional gelatin adhesives.

[Example 2]

An adhesive was prepared in the same manner as in Example 1, except that collagen, butterfly, and water were mixed in a weight ratio of 2: 2: 1.

The adhesive was applied between the wood and the fingers, and then the adhesive was applied for 3 minutes under pressure. As a result, the adhesive strength was sustained for 5 minutes or more and 100 g. In addition, after applying the adhesive between the wood and the wood, it was adhered by applying pressure for 3 minutes, and after confirming the adhesion, it sustained a load of 100 g over 5 minutes.

As a result of the animal test, it was confirmed that the initial adhesive strength was excellent. Specifically, the muscle adhesion lasted for about 2 to 3 minutes, and the conjunctiva was also adhered.

[Comparative Example 1]

An adhesive was prepared in the same manner as in Example 1, except that collagen and water were mixed in a weight ratio of 1: 1.

As a result of the adhesion test according to the bonding temperature, when the wood was bonded at room temperature, it was able to withstand a load of 100 g, but when it was bonded at 40 ° C., it could not withstand a load of 100 g. That is, although the adhesive force is generated when it is cooled at room temperature, the adhesive force is lowered at a temperature of 40 ° C, which is similar to human body temperature.

Further, as shown in Fig. 4, the tensile strength of about 1.1 N was exhibited.

Animal experiments showed that gelatin glue did not stick well to rabbit sclera and muscle. That is, the adhesive strength was lowered under the condition of body temperature and moisture.

[Comparative Example 2]

An adhesive was prepared in the same manner as in Example 1, except that collagen and water were mixed in a weight ratio of 1: 2.

As can be seen from Fig. 5, the tensile strength of this adhesive was about 4N.

[Comparative Example 3]

An adhesive was prepared in the same manner as in Example 1, except that collagen and water were mixed in a weight ratio of 2: 1. However, it was difficult to make it easily because of low fluidity due to high viscosity in the process of changing to a sol state in the production of an adhesive.

After warming the adhesive at 60 ° C using a syringe, gelatin adhesive was applied to the fingers to test the adhesive strength at body temperature, and the wood was bonded at room temperature and could not withstand a load of 100 g.

[Comparative Example 4]

An adhesive was prepared in the same manner as in Example 1, except that collagen and arabic gum solutions were mixed in a weight ratio of 1: 2.

As can be seen from Fig. 6, the tensile strength of this adhesive was about 5 N.

[Comparative Example 5]

An adhesive was prepared in the same manner as in Example 1 except that collagen, water and arabic gum solutions were mixed in a weight ratio of 2: 1: 1.

Trees and fingers, wood and water fingers, and vinyl and vinyl were bonded together and could not withstand a load of 100 g. That is, it was confirmed that the arabic gum solution had no effect on the increase of the adhesion.

Because of the high viscosity of the adhesive, it was difficult to inject when using the injector.

[Comparative Example 6]

An adhesive was prepared in the same manner as in Example 1, except that collagen and arabic gum solutions were mixed in a weight ratio of 1: 1.

Trees and fingers, wood and water fingers, and vinyl and vinyl were bonded together and could not withstand a load of 100 g.

Animal adhesion experiment was performed, but it was confirmed that no adhesion was observed to the rabbit muscle or sclera.

[Comparative Example 7]

An adhesive was prepared in the same manner as in Example 1, except that collagen, water and masking solution were mixed in a weight ratio of 2: 1: 1.

Trees and fingers, wood and water fingers, and vinyl and vinyl were bonded together. As a result, the wood and finger tests withstood a load of 100 g, but the others were not able to withstand a load of 100 g. That is, it was confirmed that the masking material for painting did not affect the increase of the adhesive strength.

[Comparative Example 8]

Collagen and masking solution were mixed in a weight ratio of 1: 1, but it was not changed into a sol state, and it was confirmed that it was difficult to use as an adhesive.

[Comparative Example 9]

Unlike Example 1, collagen and bean sprouts were mixed and heated at a weight ratio of 1: 1 without mixing water, but they did not change into a sol state, and therefore, it was difficult to produce an adhesive.

[Comparative Example 10]

An adhesive was prepared in the same manner as in Example 1, except that collagen, butterfly, and water were mixed in a weight ratio of 2: 1: 2.

As a result of measuring the bonding time by the same experimental method as that of Example 1, it was confirmed that it was able to withstand a load of about 100 g for about 5 minutes.

[Comparative Example 11]

An adhesive was prepared in the same manner as in Example 1, except that collagen, butterfly, and water were mixed in a weight ratio of 2: 1: 3.

The adhesion time was measured by proceeding in the same experimental manner as in Example 1. As a result, it was not able to withstand a load of 100 g or more for 5 minutes or more.

[Comparative Example 12]

An adhesive was prepared in the same manner as in Example 1, except that collagen, butterfly, and water were mixed in a weight ratio of 2: 1: 4.

The adhesion time was measured by proceeding in the same experimental manner as in Example 1. As a result, it was not able to withstand a load of 100 g or more for 5 minutes or more.

[Comparative Example 13]

An adhesive was prepared in the same manner as in Example 1 except that collagen, butterfly, and water were mixed in a weight ratio of 2: 3: 1.

The adhesion time was measured by the same experimental method as in Example 1. As a result, it was confirmed that the adhesive was able to withstand a load of about 100 g for about 4 minutes.

[Comparative Example 14]

An adhesive was prepared in the same manner as in Example 1, except that collagen, butterfly, and water were mixed in a weight ratio of 2: 4: 1.

The adhesion time was measured by proceeding in the same experimental manner as in Example 1. As a result, it was not able to withstand a load of 100 g or more for 5 minutes or more.

[Comparative Example 15]

An adhesive was prepared in the same manner as in Example 1, except that collagen, butterfly, and arabic gum were mixed in a weight ratio of 1: 1: 1.

After applying the adhesive between the wood and the wood, it was adhered by applying the pressure for 3 minutes, and the adhesive strength was confirmed, and it sustained a load of 100 g over 5 minutes. However, when the adhesive was applied between the wood and the fingers, the adhesive was applied for 3 minutes under pressure. As a result, it was not able to withstand a load of 100 g over 5 minutes.

[Comparative Example 16]

An adhesive was prepared in the same manner as in Example 1, except that collagen, butterfly, and arabic gum were mixed in a weight ratio of 2: 2: 1.

After applying the adhesive between the wood and the fingers, the adhesive was applied for 3 minutes under pressure. As a result, the load of 100g was sustained for 5 minutes or more. In addition, the adhesive was applied between the wood and the wood, and then the adhesive was applied for 3 minutes under pressure. As a result, the load was more than 5 minutes and the load was 100 g.

However, as a result of animal experiments, it was confirmed that no adhesion occurred. Based on the adhesive viscosity of the arabic gum solution, it was expected that the adhesiveness of the adhesive mixed with the bean sprouts would be increased, but the adhesive strength was lowered. That is, it was confirmed that when the arabic gum solution was mixed, the viscosity of the adhesive was increased but the adhesive strength was lowered. Thus, it was confirmed that the arabic gum solution can not be used as a crosslinking agent.

[Comparative Example 17]

After the root of the knot was placed in the room at room temperature for about 24 hours, the juice from the surface of the root was collected several times using a syringe.

Collagen and yugaepisin juice were mixed at a weight ratio of 1: 1, but they did not change into a sol state, and it was confirmed that it was difficult to make a gelatin adhesive.

[Comparative Example 18]

An adhesive was prepared in the same manner as in Example 1, except that the weight ratio of collagen, sesame oil, and water was 2: 1: 1.

After applying the adhesive between the wood and the fingers and applying the pressure for 3 minutes, it was confirmed that the adhesive force was not able to withstand the load of 100 g over 5 minutes. Also, the adhesive was applied between the wood and the wood, and then the adhesive was applied by applying pressure for 3 minutes. As a result, it was not able to withstand a load of 100 g over 5 minutes.

[Comparative Example 19]

An adhesive was prepared in the same manner as in Example 1, except that collagen, kerosene, and water were mixed in a weight ratio of 2: 2: 1.

After applying the adhesive between the wood and the fingers and applying the pressure for 3 minutes, it was confirmed that the adhesive force was not able to withstand the load of 100 g over 5 minutes. Also, the adhesive was applied between the wood and the wood, and then the adhesive was applied by applying pressure for 3 minutes. As a result, it was not able to withstand a load of 100 g over 5 minutes.

[Comparative Example 20]

An adhesive was prepared in the same manner as in Example 1, except that collagen, titanium dioxide powder and water were mixed in a weight ratio of 1: 1: 2.

After warming at 60 ° C, it was bonded at room temperature for 1 minute, and a weight of 100 g load was connected. As a result, the adhesion was maintained for 5 minutes or longer.

However, as a result of the animal test, initial adhesion failed, and it was confirmed that adhesion of the adhesive agent and the tissue deteriorated after a certain time after the adhesion.

[Comparative Example 21]

An adhesive was prepared in the same manner as in Example 1, except that the collagen and mussel adhesive substance extract (cell-tak) were mixed in a weight ratio of 1: 1.

After warming the adhesive, the adhesive was applied to the wood at room temperature and maintained at 40 ° C. As a result, the adhesion was maintained for 5 minutes or more in a temperature-like environment.

Animal experiments showed that the initial adhesion was successful, but after 5 days, the adhesive site was separated and the adhered muscles and tissues were pushed into the rabbit 's eyeball.

[Comparative Example 22]

An adhesive was prepared in the same manner as in Example 1 except that collagen, agar, and water were mixed in a weight ratio of 1: 1: 1.

As a result of the adhesion test, the adhesive strength was not maintained for 5 minutes or more. Agar increased viscosity when mixed with collagen, but did not lead to increased adhesion.

[Comparative Example 23]

An adhesive was prepared in the same manner as in Example 1, except that collagen, rosin and water were mixed in a weight ratio of 2: 0.5: 3.

As a result of the adhesion test, the adhesive strength was not maintained for 5 minutes or more.

[Comparative Example 24]

An adhesive was prepared in the same manner as in Example 1 except that collagen, agar, arabic rubber solution and water were mixed in a weight ratio of 2: 1: 0.5: 2.

As a result of the adhesion test, the adhesive strength was maintained for 5 minutes or more. However, the results of the animal test showed that the adhesion was not achieved and the muscle was pushed.

[Comparative Example 25]

An adhesive was prepared in the same manner as in Example 1 except that collagen, sugar and water were mixed in a weight ratio of 2: 1: 1.

As a result of the adhesion test, the adhesive strength was not maintained for 5 minutes or more.

10: Body
20: injection means
30: Heating means

Claims (20)

Collagen, water repellent, and water in a weight ratio of 2: 0.5 to 2.5: 0.5 to 1.5.
delete The method according to claim 1,
Wherein the adhesive is maintained for at least 5 minutes against a load of 100 g after the adhesive is adhered.
The method according to claim 1,
Wherein the adhesive has a tensile strength of 5 N or more.
The method according to claim 1,
Wherein the adhesive is capable of reversible change in gel state and sol state based on 40 ± 5 ° C.
The method according to claim 1,
Wherein the adhesive is usable as a tissue adhesive or a hemostatic agent.
Mixing and heating collagen, bevulap, and water in a weight ratio of 2: 0.5 to 2.5: 0.5 to 1.5 to form a sol mixture; And
And cooling the mixture to form a gel-state adhesive.
8. The method of claim 7,
Wherein the heating temperature is 40 to 100 占 폚.
8. The method of claim 7,
And then vacuum-packaged and then stored at low temperature or in freezer.
materials; And
A biomedical adhesive film formed on a substrate and comprising an adhesive layer containing collagen, water repellent and water in a weight ratio of 2: 0.5 to 2.5: 0.5 to 1.5.
11. The method of claim 10,
Wherein the base material is a release paper.
A core containing collagen, boehmite and water in a weight ratio of 2: 0.5 to 2.5: 0.5 to 1.5; And
A bioabsorbable adhesive capsule comprising a shell formed on the outside of a core.
13. The method of claim 12,
Wherein the core is in a sol state or a gel state.
13. The method of claim 12,
Wherein the shell is an adhesive film containing collagen.
Injection means for injecting into the living body an adhesive containing collagen, water bevel and water in a weight ratio of 2: 0.5 to 2.5: 0.5 to 1.5; And
And a heating means for heating the injection means.
16. The method of claim 15,
Wherein the injection means is a syringe.
17. The method of claim 16,
Wherein the syringe is installed in a replaceable form in a thermostatic injector.
16. The method of claim 15,
Wherein the heating means is a heat ray element.
19. The method of claim 18,
Wherein the heat ray element is embedded in a silicon material.
19. The method of claim 18,
Wherein the electric current applied to the hot wire element is 40 to 100 mA and the voltage is 40 to 100 V.

Images