KR102085088B1 - Method for fabricating biocompatible porous structured block and biocompatible porous structured block fabricated thereby - Google Patents

Abstract

 The present invention is to produce a porous structure with a lot of pores therein using a bio-compatible polymer material, to be applied to the surgical site of surgical patients such as cervical cancer to absorb blood or human-derived solution and to facilitate hemostasis and tissue regeneration The present invention relates to a method for preparing a porous biocompatible polymer structure to help recover the treatment of a surgical patient, and furthermore, the porous biocompatible polymer structure according to the present invention may be prepared after the preparation to include a drug to help hemostasis and tissue regeneration of tissue at the surgical site. The present invention relates to a porous biocompatible polymer structure that allows the drug to be released slowly so that the healing of the wound progresses more rapidly.

Description

Method for preparing porous biocompatible polymer structure and porous biocompatible polymer structure produced by the present invention

The present invention relates to a method for producing a porous structure having a lot of pores therein using a biocompatible polymer material, and more particularly, to a porous structure produced by the present invention, to be used in contact with or inserted into a human body. It relates to a method for producing a porous structure that can be used as a medical material and a porous structure produced thereby.

Porous structures or membranes are commonly used in water treatment processes. In the process of removing salt from seawater to make freshwater, the seawater desalination process is carried out using membranes with pores of various sizes. In addition, in the process of domestic sewage or industrial wastewater treatment, it is possible to remove contaminants by the pore size by a physical method using a porous structure or a membrane having pores of various sizes. Then, the porous structure is put into the column by the chemical affinity method, and the solution to be treated is injected. The organic compound or ionized heavy metal having a specific functional group is chemisorbed by the chemical affinity while passing through the porous structure inside the column. Can be removed

On the other hand, the porous structure or membrane is made of a fiber material that is not biotoxic as a medical material and made like a gauze or a bandage and wrapped in a damaged tissue of a burn patient or a surgical patient to absorb blood or dust from the damaged skin tissue. Prevents contaminants from coming into direct contact with damaged skin tissue.

However, the porous material based on the fiber material currently used for medical use has limitations in shape maintenance, miniaturization, and blood absorption to be used for damaged skin tissue. In particular, there is a need for a biocompatible porous structure for use in damaged tissues of surgical patients such as cervical cancer surgery. It is difficult to use the above gauze or bandages in such places.

Korea Patent Registration No. 10-1019186 (Registration Date: 2011.02.24.) Korean Patent Registration No. 10-1684790 (Registration Date: 2016.12.02.) Japanese Patent No. 4353510 (Registration Date: 2009.08.07.)

The present invention has been devised to solve the above problems, and an object of the present invention is to manufacture a structure having a lot of pores therein using a biocompatible polymer material, and to include a lot of internal pores in order to improve the absorption rate of the solution. To provide a method for producing a biocompatible polymer structure.

Each process of preparing a porous biocompatible polymer structure according to the present invention comprises the steps of preparing a mixed solution of one or two or more biocompatible polymer solutions and a curing agent in a proportion; Preparing a structure solution by mixing a predetermined ratio of the water-soluble polymer powder to the mixed solution; Pouring the structure solution into a mold having a predetermined shape; Adding heat or ultraviolet rays to advance the curing reaction of the structure solution; Releasing the cured structure from the mold after the curing reaction of the structure solution; Dissolving and removing the water-soluble polymer powder included in the cured structure using water; And drying the cured structure after dissolution removal of the water soluble polymer powder.

Preferably, the biocompatible polymer solution does not exhibit biotoxicity even when used in contact with the human body or inserted into the human body, and includes a polymer in which a curing reaction proceeds by adding heat or ultraviolet irradiation to cause solidification by increasing molecular weight. Characterized in that.

Preferably, the polymer may include any one or a mixture of polymers that undergo a curing reaction by heat and polymers that undergo a curing reaction by ultraviolet irradiation, and the polymer that undergoes a curing reaction by heat, The polymer is selected from a silicone elastomer and a polymer comprising an epoxy functional group or a urethane functional group, and the polymer undergoing a curing reaction by ultraviolet irradiation is selected from a polymer including an acrylate functional group and a polymer including a methacrylate functional group. .

Preferably, the silicone elastomer is polydimethylsiloxane (PolyDiMethylSiloxane, PDMS) is characterized in that.

Preferably, the acrylate functional group-containing polymer is characterized in that it is selected from polyethylene glycol methyl ether acrylate (PEGMEA) and polyethylene glycol diacrylate (PEGDA).

Preferably, the curing agent may be a thermal curing initiator and / or an ultraviolet curing initiator as to proceed the curing reaction by heat or ultraviolet rays, characterized in that 0.1 to 10% by weight relative to the biocompatible polymer solution do.

Preferably, the water-soluble polymer powder has a property of dissolving upon contact with water and is harmless without biotoxicity. It is characterized by.

Preferably, the hydroxyl group-containing polymer is characterized in that the polyethylene oxide (Poly (ethylene oxide)).

Preferably, in the step of adding the heat or ultraviolet light, it promotes the reaction of the biocompatible polymer solution and the curing agent to increase the molecular weight and solidification proceeds when the heat is applied in the range of 30 ℃ to 250 ℃ and UV When it is added, it is characterized in that the light of 200 nm to 400 nm wavelength is added for a certain time.

Preferably, in the step of dissolving and removing the water-soluble polymer powder, the water-soluble polymer powder contained in the hardened structure is dissolved in water and eluted by putting the cured structure in a water bath containing excess water for a long time. It is characterized by.

Preferably, in the drying step, by maintaining the cured structure under a temperature condition of room temperature to 250 ℃ for a predetermined time, the water contained in the cured structure after elution removal of the water-soluble polymer powder is evaporated to remove the A large amount of pores are formed in the cured structure.

Furthermore, the present invention provides a porous biocompatible polymer structure prepared by the above method.

According to the present invention, the solution absorption rate of the porous biocompatible polymer structure having many pores therein is high, and when applied to a burn or surgical site, it effectively absorbs blood or human-derived solution to increase the regeneration efficiency of damaged skin tissue. Because porous biocompatible polymer structure is applied to damaged skin tissue, secondary infection can be prevented by preventing contact with external pathogenic microorganisms or organic and inorganic contaminants.Tissue damage due to skin damage caused by burns or cervical cancer surgery, etc. It can be used to absorb blood or human-derived solution in the process of treatment and to allow for rapid tissue regeneration.

In addition, according to the present invention, since various kinds of biocompatible polymer materials can be used to cure and react by addition of heat or ultraviolet rays, flexible porosity can be achieved by adjusting the type of polymer materials and curing reaction conditions according to the purpose of use. The structure may be prepared or a rigid porous structure having a high hardness may be produced. Therefore, in addition to the use to apply to the damaged tissue can also be used to apply to the surface of the medical tool and can be used in a variety of manufacturing, such as plate-like or cylindrical as a single material has a wide range of applications.

According to the present invention, it is also possible to prepare a specific drug by mixing a biocompatible polymer solution for producing a porous structure. By preparing and using the porous biocompatible polymer structure containing the drug as described above, the therapeutic effect can be further improved by simultaneously releasing the therapeutic drug with absorption removal of blood or solution of damaged skin tissue.

In addition, according to the present invention, it is possible to use a frame of various shapes and sizes in the manufacturing process, it is possible to manufacture a micrometer-sized microstructure to a large material ranging from several meters or more. Therefore, the application range of the porous biocompatible polymer structure can also be widely used.

1 shows a process for preparing a porous biocompatible polymer structure according to the present invention.
Figure 2 shows a porous biocompatible polymer structure prepared according to the present invention, Figure 2 (a) is a biocompatible polymer solution PEGDA (Poly (ethylene glycol) diacrylate) and PEGMEA (Poly (ethylene glycol) methyl ether acrylate) in a composition ratio of 3 to 1 and 30 wt% of polyvinylpyrrolidone (PVP) as a water-soluble polymer powder in a mixed solution of 3 wt% of 2-Hydroxy-2-methylpropiophenone as an ultraviolet curing agent. After the solution is prepared, it is a porous structure prepared by irradiating UV light for 5 seconds, and (b) of FIG. ) 30% by weight of polyvinylpyrrolido as a water-soluble polymer powder in a mixed solution of methyl ether acrylate) in a composition ratio of 1 to 1 and 3% by weight of 2-hydroxy-2-methylpropiophenone as an ultraviolet curing agent. ne) is a porous structure prepared by the process of irradiating ultraviolet light for 5 seconds after the preparation of the structure solution by mixing, (c) of Figure 2 is a biocompatible polymer solution PEGDA (Poly (ethylene glycol) diacrylate) and 30% by weight of a water-soluble polymer powder in a mixed solution obtained by mixing PEGMEA (Poly (ethylene glycol) methyl ether acrylate) in a composition ratio of 1 to 3 and 3% by weight of 2-Hydroxy-2-methylpropiophenone as an ultraviolet curing agent. Polyvinylpyrrolidone (PVP) is a porous structure prepared by a process of irradiating UV light for 5 seconds after preparing the structure solution by mixing.
3 is an enlarged micrograph showing the porous structure of the porous biocompatible polymer structure prepared according to the present invention. FIG. 3 (a) is a micrograph of the porous structure prepared in FIG. 2 (a). 3B is a micrograph of the porous structure manufactured in FIG. 2B, and FIG. 3C is a micrograph of the porous structure manufactured in FIG.
Figure 4 shows the solution absorption of the porous biocompatible polymer structure prepared according to the present invention, Figure 4 (a) shows the composition ratio of PEGDA and PEGMEA 1 to 3 as prepared in Figure 2 (c) It is a porous structure prepared to have a photograph before the absorption of rhodamine solution, Figure 4 (b) is a porous structure prepared to have a composition ratio of 1 to 3 PEGDA and PEGMEA as prepared in Figure 2 (c) of 25 mg The photograph after absorption of / L rhodamine solution.
Figure 5 shows the absorption rate of rhodamine solution according to the content of the PVP polymer added in the process of manufacturing a porous biocompatible polymer structure prepared by the present invention.
Figure 6 shows the solution absorption of the various porous polymer structures prepared using a single or a plurality of biocompatible polymers, 3% curing agent and 30% PVP polymer in the process of preparing a porous biocompatible polymer structure prepared by the present invention Figure 6 (1) is the absorption rate of 1X PBS buffer solution of the structure prepared using the PEGDA polymer and 30% PVP polymer, Figure 6 (2) is a mixture of PEGDA and PEGMEA 3 to 1 30 Absorption rate of 1X PBS buffer solution of the structure prepared by adding% PVP polymer, Figure 6 (3) is a 1X PBS buffer solution of the structure prepared by mixing PEGDA and PEGMEA 1 to 1 and adding 30% PVP polymer 6 (4) is the absorption rate of 1X PBS buffer solution of the structure prepared by mixing PEGDA and PEGMEA 1 to 3 and adding 30% PVP polymer, Figure 5 (5) is a PEGMEA polymer Made with 30% PVP Polymer Absorption rate of 1 × PBS buffer solution of the construct.

In the following description of the present invention, if it is determined that detailed descriptions of related known functions or configurations may unnecessarily obscure the subject matter of the present invention, the detailed description thereof will be omitted.

Embodiments according to the concepts of the present invention may be variously modified and may have various forms, and specific embodiments will be illustrated in the drawings and described in detail in the present specification or application. However, this is not intended to limit the embodiments in accordance with the concept of the present invention to a particular disclosed form, it should be understood to include all changes, equivalents, and substitutes included in the spirit and scope of the present invention.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Singular expressions include plural expressions unless the context clearly indicates otherwise. As used herein, the terms "comprise" or "have" are intended to indicate that there is a feature, number, step, action, component, part, or combination thereof that is described, and that one or more other features or numbers are present. It should be understood that it does not exclude in advance the possibility of the presence or addition of steps, actions, components, parts or combinations thereof.

Hereinafter, with reference to the accompanying drawings a preferred embodiment of a porous biocompatible polymer structure and a method for producing the same according to the present invention. The terms to be described below are terms defined in consideration of the functions of the present invention, and may be changed according to conventional conventions or the intention of a user. Therefore, the definition of each term should be made by reviewing the contents throughout the present specification.

Example 1 Preparation of Porous Biocompatible Polymer Structures

1 is a process diagram schematically showing a process of manufacturing a porous biocompatible polymer structure according to an embodiment of the present invention. The process for producing a porous biocompatible polymer structure of the present invention comprises the steps of preparing a mixed solution in which a single or a plurality of biocompatible polymer solutions and a curing agent are mixed at a predetermined ratio; Preparing a structure solution by mixing a predetermined ratio of a water-soluble polymer powder to the mixed solution; Pouring the structure solution into a mold having a predetermined shape; Irradiating heat or ultraviolet rays to advance the curing reaction of the structure solution; Releasing the cured structure from the mold after the curing reaction of the structure solution; Putting the cured structure into a water bath containing excess water to dissolve and remove the water-soluble polymer powder; Taking out and drying the cured structure after removing the water-soluble polymer powder out of a water tank; It is manufactured based on.

Example 2 Investigation of Porous Morphology of Porous Biocompatible Polymeric Structures

A porous biocompatible polymer structure was prepared according to the present invention and the porous structure morphology of the prepared structure was investigated in FIGS. 2 and 3.

Figure 2 shows a porous biocompatible polymer structure prepared according to the present invention, Figure 2 (a) is a biocompatible polymer solution PEGDA (Poly (ethylene glycol) diacrylate) and PEGMEA (Poly (ethylene glycol) methyl ether acrylate) in a composition ratio of 3 to 1 and 30 wt% of polyvinylpyrrolidone (PVP) as a water-soluble polymer powder in a mixed solution of 3 wt% of 2-Hydroxy-2-methylpropiophenone as an ultraviolet curing agent. After the solution is prepared, it is a porous structure prepared by irradiating UV light for 5 seconds, and (b) of FIG. 2 is a biocompatible polymer solution, PEGDA (Poly (ethylene glycol) diacrylate) and PEGMEA (Poly (ethylene glycol). ) 30% by weight of polyvinylpyrrolido as a water-soluble polymer powder in a mixed solution of methyl ether acrylate) in a composition ratio of 1 to 1 and 3% by weight of 2-hydroxy-2-methylpropiophenone as an ultraviolet curing agent. ne) is a porous structure prepared by the process of irradiating ultraviolet light for 5 seconds after the preparation of the structure solution by mixing, (c) of Figure 2 is a biocompatible polymer solution PEGDA (Poly (ethylene glycol) diacrylate) and 30% by weight of a water-soluble polymer powder in a mixed solution obtained by mixing PEGMEA (Poly (ethylene glycol) methyl ether acrylate) in a composition ratio of 1 to 3 and 3% by weight of 2-Hydroxy-2-methylpropiophenone as an ultraviolet curing agent. Polyvinylpyrrolidone (PVP) is a porous structure manufactured by a process of irradiating UV light for 5 seconds after preparing a structure solution by mixing.

3 is an enlarged micrograph showing the porous structure of the porous biocompatible polymer structure prepared according to the present invention. FIG. 3 (a) is a micrograph of the porous structure prepared in FIG. 2 (a). 3B is a micrograph of the porous structure manufactured in FIG. 2B, and FIG. 3C is a micrograph of the porous structure manufactured in FIG.

According to the present invention, as shown in FIGS. 2 and 3, porous biocompatible polymer structures were variously manufactured to have various pores.

Example 3: Rhodamine solution absorption test of porous biocompatible polymer structure

In this embodiment, to test the degree of solution absorption using the porous biocompatible polymer structure prepared in Example 2.

Figure 4 shows the solution absorption of the porous biocompatible polymer structure prepared according to the present invention, Figure 4 (a) shows the composition ratio of PEGDA and PEGMEA 1 to 3 as prepared in Figure 2 (c) It is a porous structure prepared to have a photograph before the absorption of rhodamine solution, Figure 4 (b) is a porous structure prepared to have a composition ratio of 1 to 3 PEGDA and PEGMEA as prepared in Figure 2 (c) of 25 mg The photograph after absorption of / L rhodamine solution.

In FIG. 4, the weight of the structure before absorbing the rhodamine solution was 0.0736 g, but the weight of the structure after absorbing the rhodamine solution was 0.3377 g. Therefore, the structure (0.0736 g) absorbed 0.2641 g of the rhodamine solution, through which it can be seen that the solution absorption performance of the porous biocompatible polymer structure of the present invention is excellent.

Example 4 Solution Absorption Test of Porous Biocompatible Polymer Structural Agents Prepared with Various Water Soluble Polymer Powder Contents

In the present embodiment, a predetermined amount of water-soluble polymer powder is mixed in the process of manufacturing the porous biocompatible polymer structure of the present invention, wherein the degree of porosity of the resulting structure is different depending on the content of the water-soluble polymer powder to be mixed. The absorption rate of can also be different. Therefore, in the present embodiment, after mixing the water-soluble polymer powder content in various ways to prepare a porous structure, the solution absorption rate was investigated.

The calculation of the swelling ratio used in this example used the following formula. In the equation, W _d is the weight of the porous structure in the dry state, W _s is the weight of the structure in the absorbed solution.

Figure 5 shows the absorption rate of 25 mg / L rhodamine solution according to the PVP polymer content of the water-soluble polymer powder added in the process of preparing a porous biocompatible polymer structure prepared by the present invention. In this example, polyvinylpyrrolidone (PVP) polymer was used in the range of 20% to 40% as the water-soluble polymer powder. As shown in FIG. 5, as the PVP powder content was increased during the preparation of the porous biocompatible polymer structure, the solution absorption rate increased. In addition, in the present embodiment, when the PVP content was 40%, the solution absorption rate was the highest, but it was observed that the pores inside the structure were so large that it was difficult to maintain the shape as the structure, so it was easily broken. Therefore, it was found that 30% content of PVP having good solution absorption efficiency while maintaining the shape of the physical porous structure was the optimal porous biocompatible polymer structure. However, such PVP content in the present invention is not limited to the scope of the invention.

Example 5 Solution Absorption Rate Test of Porous Biocompatible Polymer Structural Agents Prepared Using Single or Multiple Biocompatible Polymers

In the present embodiment, in the process of manufacturing the porous biocompatible polymer structure of the present invention, it is also possible to use the biocompatible polymer material as a single material, and also to mix and use a plurality of materials.

Figure 6 shows the solution absorption rate of the various porous polymer structures prepared using a single or a plurality of biocompatible polymers, 3% curing agent and 30% PVP polymer in the process of preparing a porous biocompatible polymer structure prepared by the present invention Figure 6 (1) is the absorption rate of the 1X PBS buffer solution of the structure prepared using the PEGDA polymer and 30% PVP polymer, Figure 6 (2) is a mixture of PEGDA and PEGMEA 3 to 1 30 Absorption rate of 1X PBS buffer solution of the structure prepared by adding% PVP polymer, Figure 6 (3) is a 1X PBS buffer solution of the structure prepared by mixing PEGDA and PEGMEA 1 to 1 and adding 30% PVP polymer 6 (4) is the absorption rate of 1X PBS buffer solution of the structure prepared by mixing PEGDA and PEGMEA in a one-to-three and adding 30% PVP polymer, Figure 6 (5) is a PEGMEA polymer Made with 30% PVP Polymer Absorption rate of 1 × PBS buffer solution of the construct.

As shown in this embodiment, it can be seen that the degree of solution absorption is different depending on the mixing ratio of each material when a plurality of biocompatible materials are mixed and used. In addition, depending on the type of material and the mixing ratio, not only the solution absorption rate but also hardness and long-term stability may vary.

As mentioned above, although the present invention has been illustrated and described with reference to specific embodiments, the present invention is not limited thereto, and the scope of the following claims is not limited to the scope of the present invention. It can be easily understood by those skilled in the art that can be modified and modified.

Claims (12)

Preparing a mixed solution in which a biocompatible polymer solution including polyethylene glycol methyl ether acrylate (PEPEMEA) and polyethylene glycol diacrylate (PEPEDA) and a curing agent are mixed at a predetermined ratio ;
Preparing a structure solution by mixing a predetermined ratio of the water-soluble polymer powder to the mixed solution;
Pouring the structure solution into a mold having a predetermined shape;
Adding heat or ultraviolet ray to advance the curing reaction of the structure solution;
Releasing the cured structure from the mold after the curing reaction of the structure solution;
Dissolving and removing the water-soluble polymer powder included in the cured structure using water;
Drying the cured structure after dissolution removal of the water soluble polymer powder,
The structure solution, characterized in that it comprises PEGDA and PEGMEA in a weight ratio of 1 to 3 and 30% by weight of polyvinylpyrrolidone (PVP),
Method for producing a porous biocompatible polymer structure. delete delete delete delete The method of claim 1,
The curing agent is a method for producing a porous biocompatible polymer structure, characterized in that contained 0.1 to 10% by weight relative to the biocompatible polymer solution. delete delete The method of claim 1,
In the step of adding the heat or ultraviolet light, the reaction between the biocompatible polymer solution and the curing agent promotes solidification by increasing the molecular weight, and when heat is applied, the temperature is in the range of 30 ° C. to 250 ° C. Method for producing a porous biocompatible polymer structure, characterized in that for a predetermined time to add a light of 200 nm to 400 nm wavelength. The method of claim 1,
In the step of dissolving and removing the water-soluble polymer powder with water, the water-soluble polymer powder contained in the cured structure is dissolved in water and eluted by putting the cured structure in a water bath containing excess water for a long time. Method for producing a porous biocompatible polymer structure characterized in that. The method of claim 1,
In the drying step, by maintaining the cured structure under a temperature condition of room temperature to 250 ℃ for a predetermined time, the water contained in the cured structure after elution and removal of the water-soluble polymer powder is evaporated to remove the inside A method for producing a porous biocompatible polymer structure, characterized in that a large amount of pores are formed in. 12. A porous biocompatible polymer structure produced by the process of any one of claims 1, 6 and 9-11.

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