JP3948623B2 - Gelatin-coated alginate fiber and method for producing the same - Google Patents

Description

  The present invention relates to a biodegradable and highly biocompatible fiber material and a method for producing the same.

  Alginic acid, which is known as a biocompatible material, is an acidic polysaccharide in which mannuronic acid and guluronic acid are linearly bonded, has a strong affinity for alkaline earth metal ions such as calcium ions, and takes in alkaline earth metal ions. It has the property of taking an egg box structure and gelling. Alginic acid fibers are made using this property. It is well known to those skilled in the art to produce an alginate alkali metal salt fiber by extruding an alginate solution into an aqueous solution containing alkaline earth metal ions such as calcium ions.

  Alginate fibers are used as surgical threads and other medical materials. For example, alginic acid fibers are conventionally known to be useful in the manufacture of trauma dressings and are also used in surgical threads for implantation and implantation. Thus, as alginate fiber, the thing excellent in biocompatibility, non-immunogenicity, and biodegradability is also obtained (for example, refer patent document 1).

  Gelatin, on the other hand, is manufactured by breaking down the triple helical molecule of collagen obtained from cow bone, cow skin, pig skin, fish skin, etc., and has been known to be water-soluble and digestible in vivo. Therefore, application to a medical material is being studied.

A method for producing gelatin fibers has already been devised by the present inventors, but the operation for removing the toxicity of the solvent and the coagulating liquid is complicated during molding such as spinning, and careful attention is also paid to the washing operation. It was necessary (see, for example, Patent Document 2).
Japanese National Patent Publication No. 10-502554 Japanese Patent No. 3086822

  An object of the present invention is to obtain an improved alginic acid fiber as a biocompatible material that has a smoother surface than conventional alginate fiber. In addition, gelatin fibers have to be treated with an organic solvent such as methanol in a coagulation bath after fiber production, and the manufacturing operation is complicated, so that biocompatibility is achieved in a simpler and safer manner. The purpose is to obtain the fiber.

  The present invention provides a fiber in which gelatin is coated on the surface of an alginate fiber.

  In the fiber in which gelatin is coated on the surface of the alginic acid fiber according to the present invention, the alginic acid fiber refers to a fiber composed of a metal salt of alginic acid. Alginic acid is a polysaccharide composed of D-mannuronic acid and L-guluronic acid, and the composition ratio is preferably 1: 1. Alginic acid may be commercially available, and may be obtained from seaweed, particularly brown algae.

  In addition, the source of gelatin coated on the surface of the alginate fiber in the present invention is not particularly limited, and may be derived from a commercially available product, or from connective tissues such as animals such as cows, pigs, and fish. The obtained collagen may be denatured.

  In the fiber according to the present invention, in order to improve physical properties such as elasticity, gelatin coated on the alginate fiber surface is preferably cross-linked by a cross-linking agent.

  As the crosslinking agent, for example, aldehydes such as formaldehyde, acetaldehyde, and glutaraldehyde are preferably used, and glutaraldehyde is particularly preferable.

  The present invention also includes a step of coagulating the alginate fiber and simultaneously performing gelatin coating by extruding the aqueous solution of alginic acid into an aqueous solution containing gelatin and alkaline earth metal ions. A manufacturing method is provided.

  Alkaline earth metal ions used in the method of the present invention include magnesium ions, calcium ions, strontium ions, barium ions, etc., with calcium ions being particularly preferred.

  Specifically, an alginate aqueous solution is extruded from a nozzle into an aqueous solution containing gelatin and alkaline earth metal ions, and coagulation of alginate fibers and gelatin coating are simultaneously performed.

  Alginic acid is an anionic polysaccharide that can be easily coagulated in an aqueous solution containing alkaline earth metal ions such as calcium, and gelatin has an affinity for alkaline earth metal ions such as calcium and alginic acid. Under conditions, gelatin coating is achieved. In this method, the complicated processing required in the conventional spinning of gelatin fibers is unnecessary, and the fibers can be produced by a very simple process. That is, the solvent for dissolving gelatin used in the spinning of conventional gelatin fibers and the organic solvent used for the coagulation bath are not required, so the burden on the environment is small. Furthermore, it is a highly safe material that does not require any consideration of toxicity when used as a medical material.

  As the aqueous solution containing gelatin and alkaline earth metal ions, for example, a solution obtained by dissolving gelatin in an aqueous calcium chloride solution can be used, but it is not particularly limited as long as it is an aqueous solution containing alkaline earth metal ions and gelatin. As the alkaline earth metal ion, for example, calcium ion is preferable. In this case, when the concentration of calcium ion is provided as, for example, calcium chloride, a 3% by weight calcium chloride aqueous solution is preferable.

  The concentration of the aqueous alginate solution used in the present invention is preferably 2 to 10% by weight, and most preferably 4% by weight. If the concentration is less than 2% by weight, the fibers may become thin.

  Examples of the nozzle include, but are not limited to, a metal nozzle such as a platinum nozzle. The nozzle diameter is preferably 0.05 mm to 0.2 mm, and most preferably 0.1 mm. If the caliber is too large, the fiber becomes thick, which may cause a problem that it is difficult to solidify or become brittle.

  The concentration of gelatin in the aqueous solution containing gelatin and alkaline earth metal ions is preferably 0.1 to 1.0% by weight, more preferably 0.3 to 1.0% by weight, most preferably 0. 0.7-1.0% by weight. In the case of 0.7 to 1.0% by weight, the fiber having the highest strength is produced. However, when used at a high concentration exceeding 1.0% by weight, there may be a problem that the smoothness of the surface is lost. The temperature in the alginate fiber coagulation step may be room temperature, and the time required for coating by solution treatment containing gelatin is 30 seconds to 2 minutes, preferably 30 to 60 seconds.

  The present invention also provides a method for producing a fiber in which gelatin is coated on the surface of an alginate fiber, the method further comprising the step of crosslinking the gelatin coating with aldehydes.

  Examples of aldehydes include formaldehyde, acetaldehyde, glutaraldehyde, and glutaraldehyde is particularly preferably used. Crosslinking of gelatin is achieved by passing the gelatin-coated alginate fiber produced by the above method through, for example, an alcohol solution containing glutaraldehyde. As the alcohol solution, a lower alcohol such as methanol or ethanol may be used.

  The concentration of glutaraldehyde in the cross-linking agent solution is preferably 0.06% by weight or less, and particularly preferably 0.03% by weight.

  The fiber produced by the method of the present invention is sufficiently washed and then dried under tension at room temperature to obtain the desired fiber. Washing is preferably performed with a mixed solution of lower alcohol and lower alcohol-water, and further with distilled water.

  The present invention also provides gelatin-coated alginate fibers obtained by the above method. The fiber is obtained by coating biodegradable gelatin on the surface of alginic acid, which is a biocompatible fiber. Compared to the fiber made of alginic acid alone, the fiber surface is smoothed by the gelatin coating. Since gelatin is highly bioabsorbable, it can be used in various fields such as medical materials.

  The present invention further provides a bioabsorbable material using alginate fibers whose surfaces are coated with gelatin, and a medical material. Examples of the medical material include a suture thread, a wound protective agent, an adhesion preventive agent, an artificial biofilm, a hemostatic agent, and an artificial biomaterial protective pad.

  The fiber of the present invention is biocompatible and biodegradable and is not toxic to the human body. Therefore, it is suitable for use as a medical material that contacts the body for a short period of time. In addition, when used as a pad for protecting artificial biomaterials, a cushioning function against impact is exhibited by gelatin coating on the alginic acid surface. Therefore, a pad that is more flexible than the conventional protective pad is provided.

  The fiber of the present invention can be further applied to functional food materials or film-like food packaging materials or vegetable / fruit packaging, agricultural materials, fibrous foods that activate digestive action, and cosmetic cloths. I can do it.

  The method of the present invention is a very simple method in which coagulation of alginic acid and gelatin coating can be performed simultaneously. A fiber obtained by coating the surface of an alginate fiber obtained by the method of the present invention with gelatin is excellent in biocompatibility and biodegradability and can be used in various fields.

With reference to FIG. 1, the manufacturing method of the gelatin coat alginate fiber of this invention is demonstrated.
From a nozzle (5) having a nozzle diameter of 0.05 to 0.2 mm, for example, a nozzle diameter of 0.1 mm, a pressure (2) is applied to a 2 to 10% by weight, eg, 4% by weight, aqueous alginate solution (1) with a compressor. An aqueous alginate solution is extruded into a coagulation bath (3) at room temperature and coagulated for 30 to 60 seconds.

  An aqueous solution containing gelatin and alkaline earth metal ions is previously placed in the first coagulation bath (3). The gelatin concentration is 0.1 to 1.0% by weight, for example, 1.0% by weight, and the alkaline earth metal ion is provided, for example, as a 3% by weight calcium chloride aqueous solution.

  In the first coagulation bath (3), the alginate fibers coagulate and the surface thereof is coated with gelatin.

  The gelatin coated alginate fibers formed in the first coagulation bath (3) are then transferred to a second coagulation bath (4) containing an alcohol solution containing a cross-linking agent, for example 0.03% by weight glutaraldehyde. Here, the gelatin is crosslinked by a crosslinking agent immediately after the gelatin coating is formed.

  After winding up the fiber thus obtained, after thoroughly washing with water or a mixed solution of lower alcohol and water, for example, ethanol: water = 1: 1 mixed solution, at 50 to 100 ° C. for 1 to 4 hours, Preferably, heat treatment is performed for 1 hour to complete the crosslinking reaction.

  The gelatin-coated alginate fiber crosslinked in the second coagulation bath (4) is stretched by a stretching roller (6). Stretching can be performed by, for example, two stretching rollers having different speeds. Here, the speed ratio is preferably about 1: 1.

  Next, the stretched fiber is wound up by a winding roller (7). Then, after sufficiently washing the wound fiber, it is dried under tension at room temperature to obtain a desired fiber. Washing may be performed with a lower alcohol such as methanol, ethanol, or isopropanol, or with a mixture of lower alcohol and water such as an ethanol: water = 1: 1 mixture.

  The present invention will be described in detail below with reference to examples, but the present invention is not limited thereto.

(Spinning of gelatin-coated alginate fiber)
In the following examples, sodium alginate has a molecular weight of 600,000 and a G / M ratio of 1, gelatin used bone or skin as a raw material, and an alkali (lime) treatment or acid treatment is used. .

  Sodium alginate was dissolved in pure water to prepare a 4 wt% aqueous sodium alginate solution. The solution was filtered to remove undissolved sodium alginate and impurities, packed in a column, and left for 1 to several days to degas.

  The column was pressurized with a compressor, and from a platinum nozzle (50 holes, φ0.1 mm), the first coagulation bath (calcium chloride aqueous solution (3 wt%) or calcium chloride aqueous solution containing various concentrations of gelatin (3 wt%) ) Followed by coagulation in a second coagulation bath (methanol or methanol containing various concentrations of the cross-linking agent glutaraldehyde (referred to as GA in the following diagram)).

The film was stretched by two rollers having different speeds and wound on a cassette. The wound fiber was put together with the cassette in a beaker or a stainless steel bucket, washed with methanol, and then air-dried. The spinning conditions are shown in Table 1, and the fiber strength is shown in Table 2.
FIG. 1 shows the outline of spinning, FIG. 2 shows the maximum point stress derived from Tables 1 and 2, and FIG. 3 shows the Young's modulus.

  From these charts, it is understood that the most excellent fiber characteristics can be obtained when gelatin is 0.7 to 1.0% by weight and glutaraldehyde is 0.03% by weight.

  FIG. 4 shows the change in fiber strength when the gelatin concentration is kept at 1.0% by weight and the glutaraldehyde concentration is changed. From this figure, it is understood that the glutaraldehyde concentration is preferably 0.03% by weight.

  Further, FIG. 5 shows changes in fiber strength when the glutaraldehyde concentration is kept at 0.03% by weight and the gelatin concentration is changed. From this figure, it is understood that the gelatin concentration is preferably 0.7 to 1.0% by weight.

  FIG. 6 shows a stress-strain curve when the gelatin concentration is changed to 0 to 1.0% by weight and the glutaraldehyde concentration is changed to 0 to 0.06% by weight. From this figure, it is understood that when the glutaraldehyde concentration is 0.03% by weight and the gelatin concentration is 0.7 to 1.0% by weight, good fiber characteristics, that is, excellent characteristics in strength and elasticity can be obtained. Is done.

  FIG. 7 shows gelatin-coated alginate fibers (right side, fiber diameter of about 30 μm) obtained when gelatin is 1% by weight and glutaraldehyde is 0.03% by weight, and non-gelatin coated alginate fibers (left side, fiber diameter of about 20 μm). ) Is an enlarged view of the microscope. It is understood that the surface of the fiber is smoothed by applying the gelatin coating.

It is the schematic of the spinning process of gelatin coat alginate fiber. It is a figure which shows the fiber strength of the fiber obtained when various gelatin and glutaraldehyde density | concentration were used. It is a figure which shows the Young's modulus of the fiber obtained when various gelatin and glutaraldehyde density | concentration were used. It is a figure which shows the change of the fiber strength at the time of changing the density | concentration of glutaraldehyde which is a crosslinking agent. It is a figure which shows the change of the fiber strength at the time of changing gelatin concentration. It is a figure which shows the stress-strain curve of the fiber of this invention. It is a figure which compares the surface of the alginate fiber which is not gelatin-coated with the fiber of this invention.

Explanation of symbols

1. 1. Alginic acid solution Pressure 3. First coagulation bath 4. Second coagulation bath 5. Nozzle 6. Stretching roller 7. Winding roller

Claims (16)

A fiber having an alginate fiber surface coated with gelatin , produced by a method comprising simultaneously coagulating the alginate fiber and coating the gelatin by extruding the aqueous solution of alginic acid into an aqueous solution containing gelatin and alkaline earth metal ions .   The fiber according to claim 1, wherein the gelatin coated on the surface of the alginate fiber is crosslinked by a crosslinking agent.   The fiber according to claim 2, wherein the crosslinking agent is an aldehyde.   The fiber according to claim 3, wherein the cross-linking agent is glutaraldehyde. A method for producing a fiber in which the surface of an alginate fiber is coated with gelatin, the method comprising simultaneously coagulating the alginate fiber and coating the gelatin by extruding the aqueous solution of alginic acid into an aqueous solution containing gelatin and alkaline earth metal ions.   6. The method of claim 5, wherein the alkaline earth metal ion is a calcium ion.   Furthermore, the manufacturing method of the fiber of Claim 5 or 6 including the process of bridge | crosslinking a gelatin coating with aldehydes.   The production method according to claim 7, wherein the aldehyde is glutaraldehyde.   The manufacturing method of Claim 8 whose density | concentration of glutaraldehyde in a crosslinking liquid is 0.03 weight%.   The production method according to any one of claims 5 to 9, wherein the concentration of alginic acid in the aqueous alginic acid solution is 2 to 10% by weight.   The production method according to any one of claims 5 to 9, wherein the concentration of gelatin in the aqueous solution containing gelatin and alkaline earth metal ions is 0.1 to 1.0% by weight.   The method according to claim 11, wherein the alkaline earth metal ion is a calcium ion. The bioabsorbable material using the fiber in any one of Claim 1 to 4 . A medical material using the fiber according to claim 1 . The material according to claim 14 , wherein the medical material is selected from the group consisting of sutures, wound protective agents, anti-adhesion agents, artificial biological membranes, hemostatic agents, and artificial biological material protecting pads. A functional food material, food packaging material or agricultural material using the fiber according to claim 1 .

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