JP5542080B2 - Nonwoven fabric excellent in flexibility and water retention and method for producing the same - Google Patents

Description

  The present invention relates to a sheet-like nonwoven fabric having flexibility and water retention that are alternately sparse and dense at arbitrary intervals.

  A number of medical devices made by molding biodegradable polymers are known. In particular, aliphatic polyesters such as polylactic acid, polyglycolic acid, and polycaprolactone and their copolymers are used in various medical devices. ing. For example, molded articles obtained by processing aliphatic polyester into fibers are applied to sutures, bioabsorbable sheets, and the like.

  According to the electrospinning method (also referred to as an electrostatic spinning method or an electrospinning method), a fiber having a small fiber diameter can be easily produced. According to this production method, the adhesion to the cells can be increased by increasing the surface area of the fiber structure, and therefore, its application to a carrier for cell culture or a scaffold material for regenerative medicine has been studied. Yes. The electrospinning method is a method in which a polymer solution is extruded at a constant speed from a syringe with an electrode at a high voltage and a low current, and at the same time, a discharge treatment is performed to deposit a fiber structure on a collecting electrode. For example, it has been attracting attention as a method for producing a matrix for regenerative medicine, and a sheet having a high fiber density is usually obtained only by depositing fibers on an electrode plate. Sheets obtained in this way are used predominately in areas where sheet-like materials are required, such as anti-adhesion materials and wound dressings, but are flexible such as ligament tissue-like fiber bundles and uneven organ surfaces. There is a problem that it is difficult to use in a site that requires the property because the fiber density is high, and the water retention ability is low, so that the affinity to the organ surface is poor.

  Patent Document 1 describes a method of obtaining a cotton-like fiber by installing a negative ion generator in a cylindrical shape at a fiber collection site to float the fiber and induce deposition in the air. However, the fibers obtained in the form of cotton are suitable for forming into the required shape after cell culture, as in the case of ligament tissue-like fiber bundles. It is not suitable for such cases.

  In Patent Document 2, in order to provide a material having flexibility and strength that can withstand expansion and contraction due to blood pressure and body movement, such as an artificial blood vessel, a microfiber can easily hold a pore in a base material. A method which can be fixed while being described is described. However, in order to impart flexibility, a substrate is required in addition to the ultrafine fibers, and the fibers cannot be used alone.

Patent Document 3 describes a non-woven fabric excellent in water retention to which a hydrophilic agent is applied, but there is no description of improving water retention without performing chemical treatment such as a hydrophilic agent.
Moreover, as a flexible nonwoven fabric applicable to sanitary materials, a nonwoven fabric by a dry spunlace method is known. In this method, a natural material such as cotton or rayon, or a synthetic fiber such as polyester or nylon is formed with a web (cotton-like material) by the card method, and then the fibers are entangled with each other by a high-pressure water flow.

  Patent Document 4 describes a spunlace nonwoven fabric by a wet papermaking method and hydroentanglement. In the wet papermaking method, a web is first prepared and then formed into a sheet by hydroentanglement. However, it requires a binder such as polyvinyl alcohol and requires a process for its removal, which is complicated. Moreover, the fiber length is as short as 30 mm or less, and there is a problem that it cannot be produced with long fibers. Usually, hydroentanglement is used to make a web into a sheet, and the sheet itself is hydroentangled instead of the web to create a dense structure, or to impart both moisture content and flexibility to the sheet. Not used for.

  Patent Document 5 describes a laminated sheet formed of a non-woven fabric having water retention and a waterproof layer. However, since the water-soluble thermoplastic resin is contained in the nonwoven fabric, it has water retention, and the water-insoluble thermoplastic resin alone does not improve water retention.

JP 2009-39401 A JP 2009-19300 A JP 2006-297967 A JP-A-4-222263 JP 2006-289728 A

  The problem to be solved by the present invention is to provide a sheet-like nonwoven fabric made of a biodegradable polymer that has flexibility and water retention only by its structure.

  As a result of intensive research on sheet-like nonwoven fabric having flexibility and water retention, the inventors of the present invention surprisingly changed the bulk density of a sheet-like fiber structure composed of long fibers alternately at arbitrary intervals. Thus, a sheet-like nonwoven fabric excellent in flexibility and water retention was found, and the present invention was completed.

That is, the present invention is a sheet-like nonwoven fabric made of a fiber structure of a biodegradable polymer having a fiber diameter of 500 nm to 30 μm, and the density changes alternately from 100 μm to 2 mm, and the bulk density of the sparse structure is It is a sheet-like nonwoven fabric having a bulk density of 20 to 90 kg / m ³ and a dense structure of 100 to 200 kg / m ³ .
Moreover, this invention is a manufacturing method of this sheet-like nonwoven fabric including the process of producing a fiber structure by an electrospinning method, and the process of making it into a dense structure by hydroentanglement.

  The sheet-like nonwoven fabric of the present invention is excellent in flexibility and water retention.

  Examples of the biodegradable polymer used in the present invention include polylactic acid, polyglycolic acid, polycaprolactone, polydioxic acid, lactic acid-glycolic acid copolymer, lactic acid-caprolactone copolymer, polyglycerol sebacic acid, polyhydroxyalkanoic acid, poly Examples thereof include aliphatic polyesters such as butylene succinate and aliphatic polycarbonates such as polymethylene carbonate. Preferred are aliphatic polyesters such as polylactic acid, polyglycolic acid, and lactic acid-glycolic acid copolymer, and more preferred are polylactic acid and lactic acid-glycolic acid copolymer.

  Since any biodegradable polymer is a hydrophobic polymer, the polymer itself does not have water retention. In the present invention, water retention by structure is achieved rather than water retention due to polymer properties. Therefore, any water-degradable polymer can obtain the same water retention as long as it has the structure of the sheet-like nonwoven fabric of the present invention.

  When polylactic acid is used as the biodegradable polymer, the monomers constituting the polymer include L-lactic acid and D-lactic acid, but there is no particular limitation. Further, there is no particular limitation on the optical purity and molecular weight of the polymer, the composition ratio and arrangement of the L-form and D-form, but it is preferably a polymer with many L-forms. Good.

  The biodegradable polymer used in the present invention is preferably highly pure. In particular, residues such as additives, plasticizers, residual catalysts, residual monomers, and residual solvents used in molding and post-processing are included in the polymer. Less is preferable. In particular, when used for medical treatment, it is necessary to keep it below the safety standard value.

The molecular weight of the biodegradable polymer used in the present invention is preferably 1 × 10 ^{3 to} 5 × 10 ⁶ , more preferably 1 × 10 ⁴ to 1 × 10 ⁶ , and even more preferably 5 × 10 ^{4 to} 5 ×. 10 ⁵ . The terminal structure of the polymer and the catalyst for polymerizing the polymer can be arbitrarily selected.

The fibers used in the present invention may be mixed with other polymers and other compounds as long as the intended purpose is not impaired. For example, polymer copolymerization, polymer blending, compound mixing.
The fiber used in the present invention may contain a phospholipid. Such phospholipid can be contained in an amount of 0.1 to 10% by weight based on the polymer weight. If the phospholipid content is less than 0.1% by weight, the wettability is not preferred due to the hydrophobic nature of the biodegradable polymer, and if it is more than 10% by weight, the durability of the fiber structure itself decreases, It is not preferable. The preferable content is 0.2 to 5% by weight, and more preferably 0.3 to 3% by weight.

  Such phospholipids may be extracted from animal tissue or artificially synthesized, and examples thereof include phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. One of these may be selected, or a mixture of two or more may be used. Preferred is phosphatidylcholine or phosphatidylethanolamine, and more preferred is dilauroylphosphatidylcholine or dioleoylphosphatidylethanolamine.

  The fiber structure used in the present invention consists of long fibers. The long fiber specifically refers to a fiber structure formed without adding a step of cutting the fiber in the process from spinning to processing into a fiber structure. The length of the long fiber is preferably 300 mm or more. Although there is no restriction | limiting in particular in the whole thickness of this fiber structure, Preferably it is 25 micrometers-300 micrometers, More preferably, it is 100-200 micrometers.

  Examples of the method for obtaining the long fiber used in the present invention include an electrospinning method. The electrospinning method is a method of obtaining a fiber structure on an electrode by applying a high voltage to a solution in which a polymer is dissolved in a solvent.

  The average fiber diameter of the fiber structure used in the present invention is preferably 500 nm to 30 μm. If it is smaller than 500 nm or larger than 30 μm, good characteristics cannot be obtained when it is used as a medical article with a fiber structure. A more preferable average fiber diameter is 1.0 to 10 μm, and further preferably 2.0 to 7.0 μm. In addition, a fiber diameter represents the diameter of a fiber cross section. The shape of the fiber cross section is not limited to a circle, and may be an ellipse or an irregular shape. For the fiber diameter in the case of an ellipse, the average of the length in the major axis direction and the length in the minor axis direction is calculated as the fiber diameter. When the fiber cross section is neither circular nor elliptical, the fiber diameter is calculated by approximating a circle or ellipse.

  Examples of the method for obtaining the sheet-like nonwoven fabric of the present invention include a method in which the bulk density is changed by, for example, a hydroentanglement method or a needle punching process after producing a normal sheet. Water entanglement is a method used for producing a nonwoven fabric from a cotton-like material by injecting a high-pressure water flow onto a web (cotton-like material) from a nozzle onto a net to entangle the fibers. In the needle punching process, a needle with a barb is pierced into a web and the fibers are mechanically entangled with each other, and both are used for producing a nonwoven fabric from a cotton-like material.

  Specifically, in the water entanglement method, the water is entangled by jetting a water flow with water pressure applied from a nozzle. In the nozzle head, a large number of nozzles are arranged in the width direction of the sheet so that the water pressure applied to the nozzles can be changed. The water flow from each nozzle is continuously jetted, and while the sheet is conveyed at a constant speed, the water flow is received from the front and the fibers are entangled. The number of water entanglements can be arbitrarily selected within a range that does not impair the object of the present invention, and may be entangled only once in the front or several times in front and back. As for the water pressure at the time of hydroentanglement, if the water pressure is high, the long fiber is cut, so that the sheet strength becomes weak, and if the water pressure is low, the bulk density of the sheet cannot be changed. In the present invention, both the sheet strength and flexibility are maintained within a desired range as a medium pressure.

  In the needle punching process, the entire sheet is repeatedly pierced by a needle (needle) that moves up and down at high speed, and fibers are entangled by protrusions called barbs carved in the needle. The feature of needle punching is that it is rich in bulk and does not peel between fibers.

  The width | variety which changes the bulk density of the sheet-like nonwoven fabric of this invention is 100 micrometers-2 mm, More preferably, it is 500 micrometers-1 mm. If it is 100 μm or less, it is difficult to control the bulk density, and if it is 2 mm or more, the required flexibility is not reached. Moreover, although the bulk density has a sparse part and a dense part, even if the width is the same, even if any one of the widths is thicker, there is no problem as long as it is in the above range. The sparse part is thinner than the dense part because of the water entanglement method and the needle punching process, and the film thickness is usually reduced, and irregularities are usually formed on the surface.

The bulk density of each of the sparse part and the dense part is 20 to 90 kg / m ³ , and more preferably 40 to 70 kg / m ³ in the sparse part. If it is 20 kg / m ³ or less, it is difficult to maintain the structure, and if it is 90 kg / m ³ or more, a difference from a dense part cannot be obtained. On the other hand, the dense part is 100 kg / m ³ to 200 kg / m ³ , more preferably 110 to 150 kg / m ³ . If it is 100 kg / m ³ or less, there is no difference from a sparse part and flexibility cannot be obtained. If it is 200 kg / m ³ or more, the sheet itself is too hard to obtain flexibility.

  The sheet-like nonwoven fabric of the present invention is excellent in water retention, and retains body fluids and blood when used in the body as a medical product. The water retention rate of the nonwoven fabric satisfying such conditions is usually 800 to 2000% by weight, preferably 1000 to 1500% by weight. In order to maintain such water retention, the above dense structure is important. In order to increase water retention, it is important to reduce the bulk density. However, if the bulk density is decreased, the sheet does not have a self-supporting property, and an increase in the film thickness is required. Leading to an increase in In the present invention, since the width in which the bulk density changes is from 100 μm to 2 mm, the decrease in the structure holding force of the portion where the bulk density is sparse is compensated by the dense portion. In addition, when the surface has irregularities, not only the water retention ability of each of the sparse and dense portions but also the water retention ability as a structure can be increased, and therefore the surface may have an irregular structure. Specifically, the sparse part is thinner than the dense part by the water entanglement method or the needle punching process. Water can be collected in the indented portion by the surface tension of water.

  The softness of the sheet-like nonwoven fabric can be measured by bending resistance. Specifically, it can be measured using the JISL1096 6.19.1E method (handle ohmmeter method) or the like. The bending resistance is preferably 90 mN or less, more preferably 70 mN or less. If it is 90 mN or more, the sheet lacks flexibility and is unfavorable because it lacks the ability to follow a textured surface.

  Processes such as laminating a cotton-like fiber structure on the surface of the sheet-like nonwoven fabric of the present invention and making a sandwich structure with the cotton-like structure sandwiched by the sheet-like nonwoven fabric of the present invention are intended purposes. Can be arbitrarily implemented within a range that does not impair the process.

  The fibers and fiber structures used in the present invention can be optionally subjected to coating treatment for imparting antithrombogenicity and surface coating with antibodies and physiologically active substances in medical applications. The coating method and treatment conditions at this time, and the chemicals used for the treatment can be arbitrarily selected within a range that does not damage the fiber structure and impair the purpose of the present invention.

  A drug can be optionally contained inside the fiber of the fiber structure used in the present invention. In the case of molding by the electrospinning method, the drug used is not particularly limited as long as it is soluble in a volatile solvent and does not impair the physiological activity by dissolution. Specific examples of such drugs include tacrolimus or its analogs, statins, and taxane anticancer agents. Moreover, as long as activity can be maintained in a volatile solvent, a protein formulation and a nucleic acid pharmaceutical may be sufficient. In addition to drugs, metals, polysaccharides, fatty acids, surfactants, and volatile solvent resistant microorganisms may be included.

  The sheet-like non-woven fabric of the present invention is suitably used as an artificial dura mater, an adhesion preventing material, a hemostatic material, etc. as a medical article, particularly as a protective material, covering material, or sealing material for an organ surface or wound site.

Various evaluations of the sheet-like nonwoven fabric of the present invention were carried out under the following conditions.
Water retention: A sample of 1 cm × 1 cm square was cut out, 5 μl of each sample was impregnated with water, and the water content was determined.
Water retention rate (% by weight) = (W2−W1) / W1 × 100
W1: Initial sample weight W2: Sample weight flexibility with water: (JIS-L-1906 6.19.1E method) The bending resistance was measured by the handle ohmmeter method. The sheet was evaluated in the vertical and horizontal directions.

[Example 1]
11 parts by weight of polylactic acid (molecular weight 133,000, PURAC) added with 0.4% phosphatidylcholine dilauroyl was dissolved in 79 parts by weight of dichloromethane and 10 parts by weight of ethanol to obtain a uniform solution. Using this solution, spinning was performed by an electrospinning method to prepare a sheet-like fiber structure. The inner diameter of the ejection nozzle was 0.8 mm, the voltage was 23 kV, the distance from the ejection nozzle to the cathode flat plate was 35 cm, and the humidity was 25%. The resulting fiber structure had a thickness of 80 μm and a fiber diameter of 4.8 μm. Subsequently, the sheet-like nonwoven fabric in which the streaks having a loose structure of 500 μm and the dense structure of 1 mm were formed by hydroentanglement. The bulk density of the sparse structure was 80 kg / m ³ , and the bulk density of the dense structure was 105 kg / m ³ . The water entanglement was placed on a 50 mesh metal mesh, and entangled with a high pressure water flow using a water needle tester (nozzle 0.1 mmφ, 40 kg / cm ² , speed 2 m / min, front and back 1 each) Times). The weight of the obtained sheet-like nonwoven fabric was 1.2 mg / cm ² , the water retention rate was 1566% by weight, the flexibility was 37 mN in length and 42 mN in width.

[Example 2]
11 parts by weight of polylactic acid (molecular weight 133,000, PURAC) added with 0.4% phosphatidylcholine dilauroyl was dissolved in 79 parts by weight of dichloromethane and 10 parts by weight of ethanol to obtain a uniform solution. Using this solution, spinning was performed by an electrospinning method to prepare a sheet-like fiber structure. The inner diameter of the ejection nozzle was 0.8 mm, the voltage was 23 kV, the distance from the ejection nozzle to the cathode flat plate was 35 cm, and the humidity was 25%. The resulting fiber structure had a thickness of 150 μm and a fiber diameter of 3.2 μm. Subsequently, the sheet-like nonwoven fabric in which the streaks having a loose structure of 500 μm and the dense structure of 1 mm were formed by hydroentanglement. The bulk density of the sparse structure was 70 kg / m ³ , and the bulk density of the dense structure was 110 kg / m ³ . The water entanglement was placed on a 50 mesh metal mesh, and entangled with a high pressure water flow using a water needle tester (nozzle 0.1 mmφ, 40 kg / cm ² , speed 2 m / min, front and back 1 each) Times). The weight of the obtained sheet-like nonwoven fabric was 2.9 mg / cm ² , the water retention rate was 1624% by weight, the flexibility was 49 mN in length and 61 mN in width.

[Comparative Example 1]
11 parts by weight of polylactic acid (molecular weight 133,000, PURAC) added with 0.4% phosphatidylcholine dilauroyl was dissolved in 79 parts by weight of dichloromethane and 10 parts by weight of ethanol to obtain a uniform solution. Using this solution, spinning was performed by an electrospinning method to prepare a sheet-like fiber structure. The inner diameter of the ejection nozzle was 0.8 mm, the voltage was 23 kV, the distance from the ejection nozzle to the cathode flat plate was 35 cm, and the humidity was 25%. The obtained fiber structure had a thickness of 150 μm, a fiber diameter of 4 μm, and a bulk density of 144 kg / m ³ . The weight of the obtained sheet-like nonwoven fabric was 2.9 mg / cm ² , the water retention rate was 589 wt%, the flexibility was 237 mN in length, and 288 mN in width.

[Comparative Example 2]
11 parts by weight of polylactic acid (molecular weight 133,000, PURAC) added with 0.4% phosphatidylcholine dilauroyl was dissolved in 79 parts by weight of dichloromethane and 10 parts by weight of ethanol to obtain a uniform solution. Using this solution, spinning was performed by an electrospinning method to prepare a sheet-like fiber structure. The inner diameter of the ejection nozzle was 0.8 mm, the voltage was 23 kV, the distance from the ejection nozzle to the cathode flat plate was 35 cm, and the humidity was 25%. The resulting fiber structure had a thickness of 80 μm, a fiber diameter of 5.2 μm, and a bulk density of 146 kg / m ³ . The weight of the obtained sheet-like nonwoven fabric was 1.2 mg / cm ² , the water retention rate was 733 wt%, the flexibility was 133 mN in length and 92 mN in width.

[Comparative Example 3]
11 parts by weight of polylactic acid (molecular weight 133,000, PURAC) added with 0.4% phosphatidylcholine dilauroyl was dissolved in 79 parts by weight of dichloromethane and 10 parts by weight of ethanol to obtain a uniform solution. Using this, spinning was performed by an electrospinning method to prepare a sheet-like fiber structure. The inner diameter of the ejection nozzle was 0.8 mm, the voltage was 45 kV, the distance from the ejection nozzle to the cathode flat plate was 35 cm, and the humidity was 25%. The obtained fiber structure had a thickness of 102 μm, a fiber diameter of 4.6 μm, and a bulk density of 65 kg / m ³ . The weight of the obtained sheet-like nonwoven fabric was 0.6 mg / cm ² , the water retention rate was 784 wt%, the flexibility was 125 mN in length and 119 mN in width.

  Since the sheet-like nonwoven fabric of the present invention has high flexibility, it has high followability to uneven tissue surfaces, and is also excellent in water retention, so that it can be used as a medical article, especially as a protective material or covering material for organ surfaces and wound sites. Useful.

Claims (8)

A sheet-like nonwoven fabric composed of a fiber structure of a biodegradable polymer having a fiber diameter of 500 nm to 30 μm, and the density changes alternately at intervals of 100 μm to 2 mm, and the bulk density of the sparse structure is 20 to 90 kg / m ^3, 200 kg / ^{m 3} der bulk density of 100 to dense structure is, thin sheet nonwoven fabric than the thickness dense structure portion of the sparse structure portion.   2. The biodegradable polymer is one or more polymers selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactone, polydioxic acid, lactic acid-glycolic acid copolymer, and lactic acid-caprolactone copolymer. The sheet-like nonwoven fabric described in 1.   The sheet-like nonwoven fabric according to claim 1 or 2, wherein the fiber length of the fiber structure is 300 mm or more.   The sheet-like nonwoven fabric according to any one of claims 1 to 3, wherein the fiber contains 0.1% to 1% by weight of phospholipid with respect to the biodegradable polymer.   The sheet-like nonwoven fabric according to claim 4, wherein the phospholipid is phosphatidylcholine or phosphatidylethanolamine.   The sheet-like nonwoven fabric according to claim 4, wherein the phospholipid is dilauroyl phosphatidylcholine.   The sheet-like nonwoven fabric according to claim 4, wherein the phospholipid is dioleoylphosphatidylethanolamine.   The manufacturing method of the sheet-like nonwoven fabric in any one of Claim 1 to 7 including the process of producing a fiber structure by an electrospinning method, and the process of making it into a sparse structure by hydroentanglement.