JP2006312794A - Method for producing polymer fiber - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a polymer fiber, by which a polymer fiber having an outer diameter reduced to a level of scores of nanometers is simply produced and is applicable as a scaffold material for cell adhesion and cell growth for vascularization and neurotization. <P>SOLUTION: In the method for producing a polymer fiber by an electrospinning method by which a voltage is impressed on a polymer solution and the jet of the polymer solution is sprayed to form a polymer fiber, the jet of the polymer solution is sprayed on the poor solvent of the polymer and is coagulated in a coagulating bath to form a polymer fiber on the surface of the poor solvent. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for producing a polymer fiber.

  In recent years, as a scaffold material suitable for angiogenesis, cell adhesion for nerve regeneration, and cell proliferation, it is desired to produce a nanofiber of a polymer material having high biodegradability and high biocompatibility. As a method for producing a polymer fiber, an electrospinning method has been conventionally known. This method is a method of spinning by a high voltage. Specifically, when a high voltage is applied to the polymer solution, charges are induced and accumulated on the solution surface, and when the surface tension exceeds the repulsive force of the charge, a jet of the charged solution is jetted. The jet that is jetted becomes a finer jet due to evaporation of the solvent, and finally a polymer fiber is obtained in a portion called a collector, and it is possible to produce a nanofiber with an outer diameter of several hundred nanometers. However, in order to be applied as a scaffold material for cells, it is necessary to form nanofibers of the order of several tens of nanometers having the same diameter as that of the extracellular matrix, and development of a manufacturing method therefor is required.

By the way, for example, a method of obtaining a non-woven fabric with ultrafine fibers of several tens to several hundreds of nanometers by electrospinning by dissolving silk fibroin or silk-like material in a specific solvent has been reported (for example, Patent Documents). 1). This method is effective for silk fibroin or silk-like materials, but other polymer materials have not been studied, and the development of a more optimal method for producing polymer fibers is desired. is there.
JP 2004-068161 A

  Therefore, the present invention has been made based on the background as described above, and can easily produce a polymer fiber having an outer diameter of up to several tens of nanometers, for angiogenesis and nerve regeneration. It is an object to provide a method for producing a polymer fiber that can be applied as a scaffold material suitable for cell adhesion and cell growth.

  The present invention solves the above-mentioned problems. First, a polymer fiber by an electrospinning method in which a voltage is applied to a polymer solution and a jet of the polymer solution is jetted to form a polymer fiber. In the production method, there is provided a method for producing a polymer fiber, characterized in that a jet of the polymer solution is jetted into a poor solvent of the polymer to cause a coagulation bath to form a polymer fiber on the liquid surface of the poor solvent.

  The present invention secondly provides the method for producing a polymer fiber according to the first invention, wherein the polymer poor solvent is a good solvent of the polymer solution.

  The third aspect of the present invention is characterized in that, in the first and second aspects of the invention, the poor solvent for the polymer is an organic compound, an inorganic compound, or a metal dissolved or partially dissolved. A method for producing a molecular fiber is provided.

  Fourthly, in any one of the first to third inventions, a method for producing a polymer fiber, wherein a polymer fiber is formed by jetting a jet of a polyglycolic acid solution into water. I will provide a.

  According to the first aspect of the present invention, a polymer fiber capable of having an outer diameter of up to several tens of nanometers can be easily produced by injecting a jet of a polymer solution into a poor solvent of the polymer to cause a coagulation bath. Can do.

  According to the second aspect of the invention, since the poor solvent for the polymer is a good solvent for the polymer solution, the solvent removal operation of the polymer solution after the coagulation bath of the polymer solution jet is omitted. The polymer fiber can be produced efficiently.

  According to the third aspect of the invention, the high molecular poor solvent is a solution in which an organic compound or an inorganic compound is dissolved or partially dissolved. Poor solution). Moreover, the polymer fiber which makes these various compounds a part of the structure can be manufactured by what an organic compound, an inorganic compound, or a metal melt | dissolved or partially dissolved.

  According to the fourth aspect of the present invention, a highly biodegradable material that can be applied as a scaffold material suitable for angiogenesis, cell adhesion for nerve regeneration, and cell proliferation by jetting a jet of a polyglycolic acid solution into water. Molecular nanofibers can be produced.

  The present invention has the features as described above, and an embodiment thereof will be described below.

  The polymer fiber manufacturing method of the present invention utilizes an electrospinning method in which a polymer fiber is formed by applying a voltage to a polymer solution and ejecting a jet of the solution.

  In the electrospinning method, as described above, when a voltage is applied to the polymer solution, charges are induced and accumulated on the solution surface, and when the surface tension exceeds the repulsive force of the charge, a jet of the charged solution is jetted. The jet thus jetted becomes a finer jet due to evaporation of the solvent, and finally a polymer fiber is obtained in a portion called a collector. Here, the voltage to be applied is generally about 10 kV to 30 kV, but is not limited thereto.

  The most characteristic feature of the present invention is that, in the electrospinning method, a jet of the polymer solution is jetted into a poor solvent of the polymer to cause a coagulation bath. In the conventional electrospinning method, it has been considered that the fiber expands in the process until the jet jet is accumulated in the collector, and the fiber diameter reaches several hundred nanometers. Therefore, the present invention jets a polymer solution jet into a poor solvent of the polymer to cause a coagulation bath, prevents expansion by the external pressure of the poor solvent against the nanofiber, and the outer diameter of the poor solvent liquid surface is several tens of nanometers. This makes it possible to form high-level polymer fibers.

  The polymer of the polymer solution in the present invention may be any polymer, and is preferably a biodegradable polymer such as aliphatic polyester represented by polyglycolic acid, polylactic acid, chitosan, polyvinyl alcohol, and the like. Can be illustrated. The solvent of the polymer solution is not particularly limited as long as it dissolves the polymer.

The poor solvent in the present invention refers to a solvent having low solubility with respect to the polymer in the polymer solution to be used, and the type of the poor solvent is appropriately selected according to the type of polymer to be used. The combination of the polymer and the poor solvent is not particularly limited.

  This poor solvent is preferably a good solvent for the polymer solution used. As a result, when forming a polymer fiber by coagulating a polymer solution jet in a poor solvent, the poor solvent and the polymer solution solvent are compatible with each other. The solvent removal operation of the solution can be omitted, and the polymer fiber can be produced efficiently.

  The poor solvent in the present invention may be an organic compound, an inorganic compound, or a metal in which a metal is dissolved or partially dissolved. Since the polymer poor solvent is a solution in which an organic compound or an inorganic compound is dissolved or partially dissolved, various solutions of the organic compound or the inorganic compound can be used as the polymer poor solvent (poor solution). In this case, combinations with various solvents such as a mixed solution of water-alcohol can be considered. Moreover, the polymer fiber which makes these various compounds a part of the structure can be manufactured by what an organic compound, an inorganic compound, or a metal melt | dissolved or was melt | dissolved. For example, organic compounds can include proteins, peptides, sugars, etc., inorganic compounds can include calcium chloride, phosphoric acid, metals include aluminum, gold, etc., which can be used alone or in combination. May be. This makes it possible to create a polymer fiber rich in biocompatibility and a polymer fiber excellent in conductivity.

  As a specific poor solvent to be used, for example, when polyglycolic acid is used as a polymer, water or organic solvents such as alcohols other than fluoro-based ones are considered. Further, when collagen is used as a polymer, ethanol is considered as a poor solvent, and when polyvinyl alcohol is used as a polymer, hexane is considered as a poor solvent.

  In consideration of application as a scaffold material for angiogenesis and nerve regeneration, it is preferable to use a biodegradable polymer. In this case, the combination of the polymer and the poor solvent is preferably a combination of polyglycolic acid and water. For example, as in the examples described later, the polymer is dissolved in hexafluoroisopropanol which is a good solvent. The polymer solution may be jetted into water, which is a poor solvent for polyglycolic acid, and coagulated to form a polymer fiber having a level of several tens of nanometers on the poor solvent liquid surface. Since water, which is a poor solvent for polyglycolic acid, is a good solvent for hexafluoroisopropanol, which is a solvent for the polymer solution, polymer fibers can be produced efficiently.

  The thickness (outer diameter) of the formed polymer fiber can be adjusted by the concentration of the polymer solution, the type of poor solvent, the applied voltage, the concentration of the polymer solution, the scattering distance of the jet, etc. To an outer diameter in the range of about several tens of micrometers. Also, the length of the polymer fiber can be adjusted by appropriately selecting the poor solvent to be used.

  The above method can also produce a nonwoven fabric made of polymer fibers, and can be expected not only for use in regenerative medical engineering such as scaffolding materials for angiogenesis and nerve regeneration, but also in various industrial fields. .

  Examples according to the present invention are shown below. Of course, the present invention is not limited to the above-described embodiment and the following examples, and it goes without saying that various aspects are possible in detail.

<Manufacture of nonwoven fabric made of polymer nanofibers of polyglycolic acid>
An apparatus for producing a nonwoven fabric was prepared with reference to Khil et al. (Khil MS. Et al J. Biomed. Mater. Res. Part B Appl. Biomater 72B 117-124 (2005)). FIG. 1 shows a schematic diagram of the manufacturing apparatus.

  According to FIG. 1, the nonwoven fabric manufacturing apparatus is composed of a high voltage generator, a syringe pump, a syringe, a coagulation bath, a collector, and a stainless needle. The polymer solution is introduced from the syringe into the stainless needle through the vinyl chloride by the syringe pump, and is injected into the coagulation bath disposed on the collector. Here, the introduced polymer solution is applied with a high voltage by a high voltage generator so as to become a jet.

  As the polymer solution, polyglycolic acid was dissolved in hexafluoroisopropanol to prepare solutions having concentration of 50 mg / mL and 100 mg / mL, respectively. Further, the liquid feeding speed was 10 mL / h, the applied voltage was 23 kV, and the distance between the spinning start point and the collector was set to 25 cm. Aluminum foil was used for the collector, and the coagulation bath was filled with distilled water which was a poor solvent for polyglycolic acid and a good solvent for hexafluoroisopropanol.

  When a nonwoven fabric made of polymer nanofibers was produced by electrospinning under the above conditions, a film was formed on the liquid surface. The film was carefully collected and vacuum dried overnight, and then the fine structure was observed with a scanning electron microscope. As a result, the average diameter of the polymer fiber prepared with the 50 mg / mL polymer solution was 193 nm, and the average diameter of the polymer fiber prepared with the 100 mg / mL polymer solution was 1.27 μm. In addition, for a 100 mg / mL polymer solution, the polymer fiber produced by the method of the present invention is approximately compared to the polymer fiber produced by a conventional electrospinning method (a method not using a poor solvent coagulation bath). The thickness was about 1/3.

  The observation results are shown in FIG.

  2 (a) is a polymer fiber (100 mg / mL polymer solution) produced by the method of the present invention, and FIG. 2 (b) is a polymer fiber (100 mg / mL polymer produced by a conventional method). Solution).

  FIG. 3 shows the relationship between the fiber diameter and the distribution ratio of the polymer fiber produced by the method of the present invention and the conventional electrospinning method.

  FIG. 3 (a) is a diagram showing the relationship between the fiber diameter of a polymer fiber (100 mg / mL polymer solution) produced by the method of the present invention and its distribution rate, and FIG. 3 (b) is a conventional method. It is a figure regarding the polymer fiber (100 mg / mL polymer solution) produced by (1). FIG. 3 (c) is a diagram showing the relationship between the diameter of the polymer fiber (50 mg / mL polymer solution) produced by the method of the present invention and its distribution rate, and FIG. 3 (d) is a conventional method. It is a figure regarding the produced polymer fiber (50 mg / mL polymer solution).

  From the results of FIG. 3, the polymer fiber produced by the method of the present invention has a fiber diameter distribution shifted to a narrower diameter than the polymer fiber produced by the conventional method, and the method of the present invention is highly effective. It was confirmed that it is excellent as a technique for producing molecular fibers.

It is the figure which showed typically the manufacturing apparatus of the nonwoven fabric which consists of polymer nanofiber. It is the result of having observed the polymer fiber (100 mg / mL polymer solution) produced by the method of this invention and the polymer fiber (100 mg / mL polymer solution) produced by the conventional method with the scanning electron microscope. It is the figure which showed the relationship between a fiber diameter and its distribution rate about the polymer fiber produced with the method of this invention, and the conventional electrospinning method.

Claims (4)

  In a method for producing a polymer fiber by an electrospinning method in which a voltage is applied to a polymer solution and a polymer solution jet is ejected to form a polymer fiber, the polymer solution jet is used as a poor solvent for the polymer solution. A method for producing a polymer fiber, characterized by spraying and coagulating bath to form a polymer fiber on a poor solvent liquid surface.   The method for producing a polymer fiber according to claim 1, wherein the poor solvent for the polymer is a good solvent for the solvent of the polymer solution.   3. The method for producing a polymer fiber according to claim 1, wherein the polymer poor solvent is one in which an organic compound, an inorganic compound, or a metal is dissolved or partially dissolved. The method for producing a polymer fiber according to any one of claims 1 to 3, wherein a polymer fiber is formed by jetting a jet of a polyglycolic acid solution into water.