WO2018230759A1

WO2018230759A1 - Apparatus for preparing nerve conduit

Info

Publication number: WO2018230759A1
Application number: PCT/KR2017/006621
Authority: WO
Inventors: 박기웅; 정구찬; 현정근; 김종완
Original assignee: 주식회사리온
Priority date: 2017-06-12
Filing date: 2017-06-23
Publication date: 2018-12-20
Also published as: KR101931545B1; KR20180135287A

Abstract

The present invention relates to an apparatus for preparing a nerve conduit and, more particularly, to an apparatus for preparing a porous nerve conduit using a glass fiber, which forms a microchannel by using a space between glass fibers and is uniformly pressurized, so as to minimize the defective proportion during preparation and a difference among nerve conduits depending on the positions thereof. A nerve conduit prepared according to the present invention can be formed to have different diameters and lengths, depending on a purpose and a use such that the prepared nerve conduit can be usefully used for in vitro and in vivo research on a nerve.

Description

Neural Conduit Manufacturing Equipment

The present invention relates to a neural conduit manufacturing apparatus, and more specifically, to form a microchannel by utilizing the space between the glass fibers and evenly pressed to minimize the deviation of each neural conduit due to the defective rate and location during manufacturing. The present invention relates to a porous neural conduit manufacturing apparatus using glass fibers.

If the peripheral nerves are injured by trauma, a method of anastomizing the cut sections of the cut nerves directly is performed. However, it is almost impossible to anatomize most nerves directly, and autologous nerve transplantation is performed to restore its function when direct anastomosis is impossible. However, in the case of autologous nerve transplantation, there is a disadvantage in that it is difficult to match the thickness and shape of the neural tissue to be implanted with the damaged area, there is a limit to the collectable nerves, and the function of the transplanted nerves may be degraded. have. Therefore, neural conduit is used as a method for restoring its function when a nerve defect occurs.

The nerve conduit connects both ends of the missing nerve and acts as a pathway for nerve regeneration. It fixes both ends of the cut nerve in the nerve conduit and induces nerve connections into the conduit. The use of neural conduits can prevent the penetration of scar tissue that interferes with nerve regeneration, induces the direction of nerve regeneration in the right direction, and maintains nerve regeneration promoters secreted from the nerve itself in the catheter and interferes with regeneration. The materials to be used have the advantage that they can be blocked from the outside.

The neural conduit must be biocompatible without tissue rejection, biodegradable at the time of nerve regeneration, no neural catheter removal procedure after neural regeneration, and the degradation products of the neural catheter not toxic in the body, It should have mechanical properties to maintain internal space during nerve regeneration, and have proper elasticity and tensile strength so that the terminal part of nerve conduit can be stably maintained even after movement of procedure after insertion of nerve conduit. It should be easy to prevent damage to the normal tissue around the site and to perform the procedure. Materials for such neural conduits are largely natural polymers (collagen, chitosan, etc.) and synthetic polymers (silicone, polylactic acid (PLA), polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer) (polylactic acid-co-glycolic acid, PLGA), polycaprolactone, etc. are being studied.

The most widely used natural polymer material is collagen. Collagen has been widely used as a material for neural conduits for nerve regeneration because of its excellent biocompatibility and weak antigenicity. However, collagen has to be extracted from animals, making the manufacturing process difficult, difficult to store, and not suitable for mass production. In addition, since the manufacturing cost is expensive, there is a disadvantage in that it is limited in utilization in the clinical and very weak in tensile force in vivo. In addition, synthetic polymer-based neural conduits, such as polylactic acid and polylactic acid-glycolic acid copolymers, have been tested for biocompatibility and are made of a polymer tube without pores, so they have excellent structural stability and tensile strength, but are difficult to control physical properties. There is a disadvantage that is not easy to exchange.

In order to solve this problem, the present inventor discloses neural conduit technology using glass fiber through Korean Patent Application No. 10-2014-0027854, but there is still a problem that it is not easy to exchange body fluids.

Accordingly, an object of the present invention is to provide a porous neural conduit manufacturing apparatus having a microporous structure together with a microchannel.

It is an object of the present invention to provide a device for producing a porous neural conduit using glass fibers, which forms a microchannel by utilizing the space between the glass fibers.

Another object of the present invention is to provide a porous neural conduit manufactured using the manufacturing apparatus of the present invention.

In order to solve the above problems, the present invention according to the first aspect is (a) a container having an upper channel and a lower channel and a plurality of glass fibers are inserted; (b) polymer material injection means for injecting polymer material into the container; (c) a porous neural conduit manufacturing apparatus using glass fibers including a pressurizing means for applying a high pressure in the container, wherein the pressurizing means is (i) pressurized to be connected to the pressurizing tank to apply a high pressure to the pressurizing tank; Pump; (ii) one side is connected to the pressure pump, the pressure tank is maintained at a high pressure inside; (iii) a distribution pressure control device for connecting the other side of the pressure tank to the inside of the chamber and applying high pressure to the inside of the container; And (iv) is connected to the pressure distribution control device, and provides a porous neural conduit manufacturing apparatus including a pressure chamber including the container and the injection means therein.

The distribution pressure control device may include 2 to 100 pressure control means including 1 to 100 air valves, regulators and 1 to 100 pressure release valves.

The lower channel has a smaller diameter than the upper channel and the vessel can be inclined at discrete angles.

The container may be made of a transparent material that can be visually confirmed the penetration of the polymer solution.

The present invention according to the second aspect also includes the steps of (a) inserting a plurality of glass fibers into a container having upper and lower channels; (b) injecting a polymer material into the container into which the plurality of glass fibers are inserted; (c) applying a high pressure from the channel to infiltrate the polymer material between the glass fibers; (d) separating the glass fibers from the container; And (e) immersing the separated glass fibers in water to dissolve the glass fibers, wherein step (c) comprises; (i) forming a high pressure inside the pressurized tank using a pressurized pump; (ii) pressurizing the inside of the chamber by moving air in the pressurizing tank into the pressurizing chamber by using an air valve of a distribution pressurizing control device, and penetrating the polymer material between the glass fibers; And (iii) controlling the inside of the chamber to a normal pressure by using a pressure release valve after the penetration of the polymer material between the glass fibers is completed. The method of manufacturing a porous neural conduit using the neural conduit manufacturing apparatus To provide.

The polymer material is a collagen (collagen), gelatin (gelatin), chitosan, alginate, hyaluronic acid, dextran, silk (silk), cellulose, poly Poly 3-hydroxybutyrate (PHB), polyhydroxyvalerate (PHV) and poly hydroxybutyrate-co-valerate (PHBV), polyorthoesters , Polyviniyalcohol (PVA), polyethylene glycol (poly (ethyleneglycol), PEG), polyurethane, polyacrylic acid, poly-N-isopropyl acrylamide (poly (N-isopropyl acrylamide) , Poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) copolymer (poly (ethyleneoxide) -poly (propyleneoxide) -poly (ethyleneoxide) copolymer, polydioxanone-b-caprolactone (poly ( diox anone-b-caprolactone)), poly-ε- (caprolactone) (poly (ε-caprolactone), PCL), polylactic acid (poly (lactic acid), PLA), poly-L-lactide (Poly-L- lactide, PLLA), Poly-D-lactide (PDLA), poly-D, L-lactide (PDLLA), polyglycolic acid , One or two or more mixtures selected from the group consisting of PGA) or poly (lactic acid-co-glycolic acid), PLGA; and methylene chloride, dichloromethane, DCM), 1,4-dioxane, chloroform, acetone, anisole, ethyl acetate, methyl acetate, N- Methyl-2-pyrrolidone (N-methyl-2-pyrrolidone), hexa fluoro isopropanol (HFIP), tetrahydrofuran (THF), dimethylsulfoxide (DMSO), 2-pi Lollidon (2-pyrollidone), citric acid Triethyl citrate, trifluoro acetic acid (TFA), dimethyl formamide (DMF), ethyl lactate, propylene carbonate, benzyl alcohol, One or two or more selected from the group consisting of benzyl benzoate, miglyol 810, isopropanol, isopropanol, ethanol, acetonitrile or tetraglycol (TG) Mixed solvents.

The weight / volume (w / v%) of the polymer and the solvent may be 10 to 40%.

In the step of immersing in the water, the solvent may be phase-separated from the water and separated from the polymer to form pores in the polymer.

The polymer material may be in a solution state at room temperature.

Porous neural conduit manufacturing method using the glass fiber, cooling the neural conduit formed after the step of dissolving the glass fiber with liquid nitrogen; And cutting the cooled neural conduit to form.

The pressurization may be repeated a plurality of times.

The present invention according to the third aspect also provides a porous neural conduit manufactured by the above method.

The neural conduit may have a microchannel in the axial direction of the neural conduit as the glass fiber is inserted in the axial direction of the container.

The neural conduit may form micropores in the neural conduit as the solvent is dissolved in water.

Effects according to the present invention are as follows.

1. Hydrophobic tetraglycol (TG) is penetrated through glass fiber using a mixed solvent of polylactic acid-glycolic acid copolymer (PLGA), which is a hydrophobic polymer, and tetraglycol (TG), which is a hydrophobic solvent. It is physically separated from the polymer constituting the neural conduit, thereby forming micropores capable of body fluid exchange.

2. As the melting point of the polymer solution is lowered by mixing the polylactic acid-glycolic acid copolymer (PLGA) and tetraglycol (TG), the polymer material is maintained at room temperature after the PLGA has been dissolved with TG once. Can be used without remelting.

3. After penetrating the polymer solution having a certain viscosity into the space between the glass fibers, it is possible to produce a neural conduit of uniform density by repeatedly applying a high pressure.

1 is a photograph showing a method of manufacturing a porous neural conduit; A is a glass fiber, capillary glass and capillary glass tube with glass fiber inserted, B is a silicone tube with 2-way valve and Luer lock syringe, C is a Luer lock with silicon tube with 2-way valve (Luer lock) Syringe, D pressurizes the inside of glass tube using syringe.

Figure 2 is a schematic diagram showing a method of manufacturing a porous neural conduit.

3 and 4 are diagrams showing the effect of channel formation according to discontinuous (a) or continuous (b) vessel tilt.

5 is a cross-sectional SEM image of the porous neural conduit; Scale bar = 100 μm (left) and 10 μm (right).

6 is an enlarged SEM image of the microstructure in the cross section of a porous neural conduit; Scale bar = (A, C) 10 μm, (B, D) 1 μm, ▶ = Micropores inside the channel.

7 is a longitudinal cross-sectional SEM image of the porous neural conduit; Scale bar = (A) 100 μm, (B) 10 μm, (C) 10 μm, (D) 1 μm.

8 is a photograph showing that the TG escaped from the porous neural conduit sinks below the DW; Yellow arrow: TG.

Figure 9 is a photograph showing a porous neural conduit made of various diameters and lengths according to the application.

10 is a view briefly showing a dispensing pressure control device according to an embodiment of the present invention.

The present invention (a) a container having an upper channel and a lower channel is inserted a plurality of glass fibers; (b) polymer material injection means for injecting polymer material into the container; (c) a porous neural conduit manufacturing apparatus using glass fibers including a pressurizing means for applying a high pressure in the container, wherein the pressurizing means is (i) pressurized to be connected to the pressurizing tank to apply a high pressure to the pressurizing tank; Pump; (ii) one side is connected to the pressure pump, the pressure tank is maintained at a high pressure inside; (iii) a distribution pressure control device for connecting the other side of the pressure tank to the inside of the chamber and applying high pressure to the inside of the container; And (iv) connected to the pressure distribution control device, and relates to a porous neural conduit manufacturing apparatus including a pressure chamber including the container and the injection means therein.

The present invention also includes the steps of (a) inserting a plurality of glass fibers in a container having an upper and a lower channel; (b) injecting a polymer material into the container into which the plurality of glass fibers are inserted; (c) applying a high pressure from the channel to infiltrate the polymer material between the glass fibers; (d) separating the glass fibers from the container; And (e) immersing the separated glass fibers in water to dissolve the glass fibers, wherein step (c) comprises; (i) forming a high pressure inside the pressurized tank using a pressurized pump; (ii) pressurizing the inside of the chamber by moving air in the pressurizing tank into the pressurizing chamber by using an air valve of a distribution pressurizing control device, and penetrating the polymer material between the glass fibers; And (iii) controlling the inside of the chamber to a normal pressure by using a pressure release valve after the penetration of the polymer material between the glass fibers is completed. The method of manufacturing a porous neural conduit using the neural conduit manufacturing apparatus It is about.

The term "polymeric material" is prepared by dissolving a hydrophobic polymer in a hydrophobic solvent, and in the present invention, a collagen, gelatin, chitosan, alginate, hyaluronic acid as a hydrophobic polymer. ), Dextran, silk, cellulose, poly 3-hydroxybutyrate (PHB), polyhydroxyvalerate (PHV) and polyhydrooxybutyric acid-valeric acid Copolymers (poly hydroxybutyrate-co-valerate (PHBV), polyorthoesters, polyviniyalcohol (PVA), polyethylene glycol (poly (ethyleneglycol), PEG), polyurethane, polyacrylic acid), poly (N-isopropyl acrylamide), poly (ethylene oxide) -poly (propylene oxide) -poly (ethylene oxide) copolymer (poly (ethyl eneoxide) -poly (propyleneoxide) -poly (ethyleneoxide) copolymer), polydioxanone-b-caprolactone (poly (dioxanone-b-caprolactone)), poly-ε- (caprolactone) (poly (ε-caprolactone) , PCL), poly (lactic acid, PLA), poly-L-lactide (PLLA), poly-D-lactide (PDLA), poly- D, L-lactide (PDLLA), polyglycolic acid (poly (glycolic acid), PGA) or poly (lactic acid-co-glycolic acid) (poly (lactic acid-co-glycolic acid) ), PLGA), one or more mixtures selected from the group consisting of methylene chloride (methylene chloride, dichloromethane, DCM), 1,4-dioxane (1,4-dioxane), chloroform, Acetone, anisole, ethyl acetate, methyl acetate, N-methyl-2-pyrrolidone, hexafluoroisopropanol (hexa fluoro isopropanol (HFIP), tetrahydrofuran (tetrahy drofuran (THF), dimethylsulfoxide (DMSO), 2-pyrollidone, triethyl citrate, trifluoro acetic acid (TFA), dimethylformamide formamide (DMF), ethyl lactate, propylene carbonate, benzyl alcohol, benzyl benzoate, miglyol 810 (Miglyol810), isopropanol, ethanol , One or two or more mixed solvents selected from the group consisting of acetonitrile or tetraglycol (TG) may be used. Preferably, PLGA- prepared using PLGA as a polymer and TG as a solvent. TG solution.

The hydrophobic polymer may be a polylactic acid-co-glycolic acid (PLGA), and the hydrophobic solvent may be tetraglycol (tetraglycol, TG). According to the present invention, since the PLGA is once dissolved in TG when the PLGA and TG are mixed, the solution is maintained at room temperature and thus can be used without re-melting the polymer material.

The weight / volume% (w / v%) of the polymer and the solvent refers to the weight (g) of the polymer dissolved in 1L of solvent, the weight / volume% (w / v%) is 10 to 40%, more preferably 15-25%, most optimally 20%. If less than the above range, there is a problem that the porosity is greatly increased due to the use of excessive solvent, and vice versa, sufficient pore formation may be difficult.

The pressurizing means includes: (i) a pressurizing pump connected to the pressurizing tank to apply high pressure to the pressurizing tank; (ii) one side is connected to the pressure pump, the pressure tank is maintained at a high pressure inside; (iii) a distribution pressure control device for connecting the other side of the pressure tank to the inside of the chamber and applying high pressure to the inside of the container; And (iv) a pressure chamber connected to the distribution pressure control device, the pressure chamber including the container and the injection means therein, wherein step (c) includes (i) a high pressure inside the pressure tank using a pressure pump. Forming a; (ii) pressurizing the inside of the chamber by moving air in the pressurizing tank into the pressurizing chamber by using an air valve of a distribution pressurizing control device, and penetrating the polymer material between the glass fibers; And (iii) adjusting the inside of the chamber to atmospheric pressure by using a pressure release valve after the penetration of the polymer material between the glass fibers is completed. When pressurizing the inside of the chamber by using a conventional pressure pump, it is difficult to pressurize at a constant speed, and since the pressure in the portion connected to the conduit increases faster than the pressure in the region far from the conduit, the polymer material is uniformly injected into the porous neural conduit. It is difficult. In particular, since the present invention penetrates the polymer material between the glass fibers by using pressure, the possibility of a defect in the nerve conduit becomes very high when a constant pressure is not formed. Therefore, it is preferable to pressurize at a constant speed using the pressurizing tank 400 and pressurize the inside of the chamber using the distribution pressure control device 100 so that the entire chamber has a constant pressure. In this case, the distribution pressure control device 100 includes 2 to 100 pressure control means 110 including 1 to 100 air valves 112, a

regulator

111, and 1 to 100 pressure release valves 113. It is more preferable to have a constant pressure regardless of the position inside the chamber, including. In addition, in order to automate the production of the neural conduit, the pressure pump, the pressure tank, the chamber, and the distribution pressure control device are each provided with a pressure sensor and a control means, and a conduit connecting each device is provided with a valve to automatically inside the chamber. It is desirable to be adjusted to a constant pressure.

In addition, the glass fiber may be moved by the pressure of the pressure during the pressing, it is preferable to fix the glass fiber using a fixing means. The fixing means may be any means as long as it can fix the glass fiber, but may be a wire, an elastic body or a band including a fiber, a polymer or a metal material. In addition, the fixing means is more preferably fixed to the container so that the glass fiber does not leave the position when pressed. In this case, the fixing means may be fixed to the container by using hooks, protrusions or protrusions installed on the container. In addition, the fixing means may be fixed to the glass fibers one by one, but also can be fixed by wrapping the 2 to 1000 glass fiber bundles, it is also possible to collect and fix the 2 to 100 glass fiber bundles as described above.

The lower channel has a smaller diameter than the upper channel, so that the glass fibers injected into the container can remain filled without flowing in the container.

The container may be inclined at a discontinuous angle, and more specifically, the container may be formed of upper and lower channels inclined at a discontinuous angle, but is not limited thereto.

By the container inclined at the discontinuous angle and the upper and lower channels thereof, the spacing of the glass fibers to be inserted is constant, so the spacing of the microchannels formed in the space where the glass fibers are melted is also constant. That is, the porous neural conduit manufactured according to the present invention forms microchannels at regular intervals, thereby inducing neural regeneration in the same direction.

The container may be to form a bottleneck point by heating a central portion of the glass tube to form an upper channel and a lower channel, but is not limited thereto.

The polymer material may be in a solution state at room temperature.

Porous neural conduit manufacturing method using the glass fiber, cooling the neural conduit formed after the step of melting the glass fiber with liquid nitrogen; And cutting the cooled neural conduit to form.

The container may be made of a transparent material in which the penetration of the polymer solution can be visually confirmed, but may be preferably made of glass, but is not limited thereto.

The pressing may be performed repeatedly a plurality of times, thereby producing a neural conduit of uniform density.

The present invention provides a porous neural conduit prepared according to the method of the present invention.

The neural conduit may be a microchannel formed in the axial direction of the nerve conduit as the glass fiber is inserted in the axial direction of the container. More specifically, the glass fiber is axially inserted into the upper channel of the container (glass tube), and then the polymer material (PLGA-TG solution) is injected into the container and pressure is applied to infiltrate the glass fiber and separated from the container. The glass fibers were melted by immersion in water (DW) to form microchannels made of hydrophobic polymer (PLGA) in the space where the glass fibers were melted. That is, by inserting the glass fibers in the axial direction of the container to melt the glass fibers, a neural conduit was formed in which the microchannels were formed in the axial direction in the space where the glass fibers were melted.

The term "microchannel" refers to an empty space of 10 to 20 μm size formed in the space where the glass fibers are melted.

The neural conduit may be micropores formed in the neural conduit as the solvent is dissolved in water. More specifically, TG reacts (dissolves) with water (DW) in the process of immersing glass fiber infiltrated with polymer material (PLGA-TG solution) in water (DW) and exits from the neural conduit to form micropores inside the microchannel. Formed. Dissolution in this specification means that TG is separated from the polymeric material.

The term “microporous pores” refers to the fine pores that form in the microchannels as the solvent dissolves in the DW and exits the neural conduit. The neural conduit prepared according to the present invention facilitates fluid exchange by microchannels when applied in vivo. The solvent exiting the neural conduit was denser than the DW (1.09 g / ml) and settled in a haze at the bottom of the DW (FIG. 7).

Porous neural conduit prepared according to an embodiment of the present invention can be produced in a variety of diameters and lengths, and can be freely changed in diameter and length according to the purpose and purpose of use to be useful in in vitro and in vivo studies of the nerves have.

Hereinafter, examples will be described in detail to help understand the present invention. However, the following examples are merely to illustrate the content of the present invention is not limited to the scope of the present invention. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

<실시예 1> 유리섬유를 이용한 다공성 신경도관의 제조 1Example 1 Preparation of Porous Neural Conduits Using Glass Fibers

Hydrophobic polymer polylactic acid-glycolic acid copolymer (PLGA) (mol% of lactic acid to glycolic acid, 85:15) and hydrophobic solvent tetraglycol (TG) (density: 1.09 g / ml, Sigma-Aldrich, USA ) Was mixed so that the weight-to-volume (w / v) ratio was 20% (w / v) and then dissolved at 60 ° C. for 18 hours to prepare a 20% (w / v) PLGA-TG solution (polymeric material).

The central portion of the capillary tube 1.6 mm in inner diameter and 13 cm in length was heated to form a bottleneck, forming upper and lower channels that were inclined at discrete angles. At this time, the lower channel was manufactured to form a smaller diameter than the upper channel. Thereafter, water soluble glass fibers (50P ₂ O ₅ -20CaO-30Na ₂ O in mol% (1100 ° C, 800rpm)) having a diameter of 10 to 20 μm were cut in 5 to 6 cm units to form a shaft in the upper channel of the glass tube. In the right direction (FIGS. 1A and 2A).

A pressure device prepared by connecting a Luer lock syringe with a 2-way valve attached to a silicon tube having an inner diameter of 0.8 mm and a length of 15 cm was inserted into an upper channel of a glass tube into which glass fibers were inserted (FIG. 1B and 1C).

Allow the lower channel of the glass tube to immerse in 20% (w / v) PLGA-TG solution at room temperature, inject the PLGA-TG solution into the syringe, and then repeatedly pressurize the glass tube to 20% (w / v). ) The PLGA-TG solution was allowed to fully penetrate the gaps between the glass fibers (FIGS. 1D and 2C).

In the present embodiment, as described above, the width of the lower channel is narrowed compared to the upper channel at a discontinuous angle, which is shown in FIG. 3. If the angle is continuous (Fig. 4), the gap between the glass fibers is gradually narrowed, there is a problem that it is difficult to maintain a constant gap between the glass fibers. When the spacing of the glass fibers is not constant, the nerve regeneration direction formed by the glass fibers varies depending on the channel, and thus a problem occurs that nerve regeneration in the same direction becomes difficult.

The glass fiber infiltrated with PLGA-TG solution was separated from the glass tube using a wire of 1.5 mm in diameter and 15 cm in diameter, and immediately immersed in 10-20 ° C. of distilled water (DW) for at least 24 hours (FIG. 2D). ), Approximately 7,000 to 8,500 (number of microchannels: 7,777 ±) of 10 to 20 μm microchannels (16.54 ± 3.6 μm in diameter) consisting of PLGA in the space where all the glass fibers are dissolved and the glass fibers are melted. 716.2 pieces) (FIGS. 2E and 5). At the same time as the glass fibers were dissolved in the DW of 10 ~ 20 ℃, PLGA was cured to form a microchannel. In addition, in the process of immersing the glass fiber in which the PLGA-TG solution penetrated in the DW, TG reacts with the DW (dissolves in DW) to escape from the microchannel, thereby forming micropores inside the microchannel (FIGS. 5, 6 and 7). TG released from the neural conduit was denser than the DW and sunk in the lower part of the DW (Fig. 8).

The glass fiber and TG were removed through the DW treatment, and the porous microchannel made of PLGA, that is, the prepared neural conduit was frozen in liquid nitrogen for about 30 seconds, and cut and shaped to a size suitable for use (FIG. 9).

<실시예 2> 유리섬유를 이용한 다공성 신경도관의 제조 2Example 2 Preparation of Porous Neural Conduit 2 Using Glass Fibers

In Example 1, a pressure was applied using a syringe, but a porous neural conduit was manufactured using an automatic pressure control method using a pressure chamber instead of the syringe. After preparing the same channel as Example 1, the upper channel was connected to the pressurization chamber. The

valves

112 and 113 connected to each conduit were adjusted to be OFF, and then the pressure pump 200 was operated to pressurize the pressure tank 400 to prepare. Afterwards, the chamber was pressurized to a predetermined pressure through the three pressure control means 110 connected to the distribution pressure control device 100, and after the pressurization was completed, the inside of the chamber was adjusted to the normal pressure by using each pressure release valve 113. . Thereafter, the procedure was performed in the same manner as in Example 1.

<실시예 3> 다공성 신경도관의 내부 미세구조 확인Example 3 Checking the Internal Microstructure of the Porous Neural Conduit

The microstructures formed in the microchannels inside the neural catheter prepared in Example 1 by dissolving the glass fibers in water were confirmed by scanning electron microscopy (SEM) (FIGS. 5, 6 and 7).

5 is a cross-sectional view of the neural conduit, FIG. 6 is a photograph showing an enlarged microstructure in the cross-sectional view of the neural conduit, and FIG. 7 is a longitudinal cross-sectional view of the neural conduit, in which the microchannels inside the neural conduit are continuous from the distal to the proximal end. It was confirmed that micropores were formed in the microstructure inside the microchannel.

However, when the neural conduits were manufactured by repeating the method 10 times, the size and distribution of the microchannels inside the neural conduits were not constant. On the contrary, the neural conduits were repeated 10 times by the method of Example 2. When the conduit was manufactured, it was confirmed that neural conduits including microchannels having a constant size and distribution can be produced. This is because it is determined that a constant pressure is not applied because the syringe is operated using a human sense when pressurized by the method of Example 1, and in Example 2 using a valve and a pressurized chamber, the microchannel having a constant size and distribution is neural. It was confirmed that it is distributed in the conduit.

The neural conduit prepared according to the present embodiment may be manufactured in various diameters and lengths according to the purpose and purpose of use so as to be useful for in vitro and in vivo studies of the nerve.

As described above in detail specific parts of the present invention, it will be apparent to those skilled in the art that these specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. will be. Thus, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims

(a) a container having an upper channel and a lower channel, into which a plurality of glass fibers are inserted;

(b) polymer material injection means for injecting polymer material into the container;

(c) pressurizing means for applying high pressure in the vessel;

In the porous nerve conduit manufacturing apparatus using a glass fiber comprising a,

The pressing means,

(i) a pressurized pump connected to the pressurizing tank to apply high pressure to the pressurizing tank;

(ii) one side is connected to the pressure pump, the pressure tank is maintained at a high pressure inside;

(iii) a distribution pressure control device for connecting the other side of the pressure tank to the inside of the chamber and applying high pressure to the inside of the container; And

(iv) a pressurization chamber connected to said dispensing pressure control device and including said container and injection means therein;

Porous neural conduit manufacturing apparatus comprising a.
The method of claim 1,

The dispensing pressure control device is a device for producing a porous neural conduit, characterized in that it comprises 2 to 100 pressure control means including 1 to 100 air valves, regulators and 1 to 100 pressure release valves.
The method of claim 1,

The lower channel has a smaller diameter than the upper channel, the container is a porous neural conduit manufacturing apparatus using a glass fiber, characterized in that inclined at a discontinuous angle.
The method of claim 1,

The container is a porous neural conduit manufacturing apparatus using a glass fiber, characterized in that made of a transparent material that can be visually confirmed the penetration of the polymer solution.
(a) inserting a plurality of glass fibers into a container having upper and lower channels;

(b) injecting a polymer material into the container into which the plurality of glass fibers are inserted;

(c) applying a high pressure from the channel to infiltrate the polymer material between the glass fibers;

(d) separating the glass fibers from the container; And

(e) immersing the separated glass fibers in water to dissolve the glass fibers;

Including;

Step (c) is;

(i) forming a high pressure inside the pressurized tank using a pressurized pump;

(ii) pressurizing the inside of the chamber by moving air in the pressurizing tank into the pressurizing chamber by using an air valve of a distribution pressurizing control device, and penetrating the polymer material between the glass fibers; And

(iii) adjusting the inside of the chamber to atmospheric pressure using a pressure release valve after the penetration of the polymer material between the glass fibers is completed;

Porous neural conduit manufacturing method using the neural conduit manufacturing apparatus of any one of claims 1 to 4, characterized in that it comprises a.
The method of claim 5,

The polymer material is

As a polymer, collagen, gelatin, chitosan, alginate, hyaluronic acid, dextran, silk, cellulose, polyhydrooxybutyric acid poly 3-hydroxybutyrate (PHB), polyhydroxyvalerate (PHV) and copolymer of polyhydrooxybutyrate-valeric acid (PHBV), polyorthoesters, polyvinyl alcohol (polyviniyalcohol, PVA), polyethylene (poly (ethyleneglycol), PEG), polyurethane, polyacrylic acid, poly-N-isopropyl acrylamide, poly (ethylene Oxide) -poly (propylene oxide) -poly (ethylene oxide) copolymer (poly (ethyleneoxide) -poly (propyleneoxide) -poly (ethyleneoxide) copolymer, polydioxanone-b-caprolactone (poly (dioxanone-b- caprolactone)), Paul Li-ε- (caprolactone) (poly (ε-caprolactone), PCL), poly (lactic acid, PLA), poly-L-lactide (PLLA), poly-D Poly-D-lactide (PDLA), Poly-D, L-lactide (PDLLA), polyglycolic acid (PGA) or poly (lactic acid- co-glycolic acid) (poly (lactic acid-co-glycolic acid), PLGA) one or two or more mixtures selected from the group consisting of; and

Methylene chloride, dichloromethane, DCM, 1,4-dioxane, chloroform, acetone, anisole, ethyl acetate, methyl Acetic acid (methyl acetate), N-methyl-2-pyrrolidone, hexa fluoro isopropanol (HFIP), tetrahydrofuran (THF), dimethyl sulfoxide ( dimethylsulfoxide (DMSO), 2-pyrollidone, triethyl citrate, trifluoro acetic acid (TFA), dimethyl formamide (DMF), ethyl lactate lactate, propylene carbonate, benzyl alcohol, benzyl benzoate, benzyl benzoate, miglyol810, isopropanol, ethanol, acetonitrile or tetraglycol (tetraglycol, TG) One or two or more mixed solvents selected from;

Method for producing a porous neural conduit comprising a.
The method of claim 6,

Weight / volume% (w / v%) of the polymer and the solvent is a porous neural conduit manufacturing method, characterized in that 10 to 40%.
The method of claim 6,

The solvent is a method of manufacturing a porous neural conduit, characterized in that the pores are formed in the polymer by being separated from the polymer by phase separation from the water in the step of immersing in the water.
The method of claim 5,

The polymer material is a porous neural conduit manufacturing method using a glass fiber, characterized in that the solution state at room temperature.
The method of claim 5,

Porous neural conduit manufacturing method using the glass fiber,

Cooling the neural conduit formed after dissolving the glass fibers with liquid nitrogen; And

Porous neural conduit manufacturing method using a glass fiber, characterized in that it further comprises the step of forming the cooled neural conduit.
The method of claim 5,

The pressurization is a porous neural conduit manufacturing method using a glass fiber, characterized in that the process is repeated a plurality of times.
Porous neural conduit prepared by the method according to claim 5.
The method of claim 12,

The neural conduit is a porous neural conduit, characterized in that the microchannel is formed in the axial direction of the nerve conduit as the glass fiber is inserted in the axial direction of the container.
The method of claim 12,

The neural conduit is a porous neural conduit characterized in that the fine pores are formed in the neural conduit as the solvent is dissolved in water.