WO2011138974A1 - Matériau de renforcement pour une colle biologique, et procédé de production de celui-ci - Google Patents

Matériau de renforcement pour une colle biologique, et procédé de production de celui-ci Download PDF

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WO2011138974A1
WO2011138974A1 PCT/JP2011/061008 JP2011061008W WO2011138974A1 WO 2011138974 A1 WO2011138974 A1 WO 2011138974A1 JP 2011061008 W JP2011061008 W JP 2011061008W WO 2011138974 A1 WO2011138974 A1 WO 2011138974A1
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Prior art keywords
molded body
glue
fiber molded
reinforcing material
biological
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PCT/JP2011/061008
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English (en)
Japanese (ja)
Inventor
勧 本多
由佳子 景山
真 佐竹
博章 兼子
澄香 宮柱
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帝人株式会社
一般財団法人化学及血清療法研究所
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Priority to JP2012513839A priority Critical patent/JP5479584B2/ja
Publication of WO2011138974A1 publication Critical patent/WO2011138974A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
    • A61L24/0094—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing macromolecular fillers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0042—Materials resorbable by the body

Definitions

  • the present invention relates to a bioglue reinforcing material comprising a fiber-molded body of a bioabsorbable polymer, a method for producing the same, and an artificial biofilm made of the reinforcing material and biopaste.
  • the reinforcing material for living body paste is made of a fine fiber molded body having no through-hole larger than a specific size and can be combined with the living body glue on the living body membrane.
  • This artificial biological thin film is preferably used as a prosthetic substitute dura mater, an adhesion prevention material, a hemostatic material, etc., as a medical article, especially as a protective material, covering material, or sealing material for an organ surface or wound site.
  • the needle hole once opened is difficult to close, and when the tension is applied, the needle hole through which the thread passes may be stretched, and cerebrospinal fluid is likely to leak from the needle hole. It was. Therefore, a filling method in which fibrin glue is applied to the suture portion of the artificial substitute dura is employed.
  • the artificial substitute dura mater is mainly composed of a polymer compound of PTFE (polytetrafluoroethylene), so that it has a low affinity with fibrin glue and cannot completely close the needle hole. ing.
  • 11-309151 describes that a bioabsorbable woven fabric impregnated with an aqueous solution of a biological glue precursor is used as a filling material for a suture portion in order to solve the problem of the filling method. .
  • the invention since it is limited to use as a filling material / reinforcing material at the suture site, the invention has not led to the invention of an artificial substitute dura mater that does not require suture.
  • Seam Dura registered trademark: Gunze Co., Ltd.
  • sutures are necessary to prevent liquid leakage, which is troublesome for the operator. Therefore, an artificial substitute dura mater that does not require suturing and has high affinity with fibrin glue has been desired.
  • Japanese Patent Application Laid-Open No. 2004-089361 describes an artificial substitute dura mater in which the surface of PTFE is modified by an ion beam to improve the affinity with a biological tissue adhesive (fibrin glue) and a method for producing the same. . Although it has become possible to use without stitching due to the increased affinity with fibrin glue, the non-degradability of PTFE has not changed, leaving the problem of remaining permanently in the body.
  • Japanese Patent Application Laid-Open No. 2002-204826 discloses an artificial living body in which a bioabsorbable and / or biodegradable synthetic fiber cloth having a network structure of 0.1 mm 2 to 25 mm 2 is coated with a membrane mainly composed of fibrin fibers. A thin film is described.
  • WO2006 / 025150 uses an intestinal defect occlusion device made of polyglycolic acid felt and fibrin glue so that it can be used for occlusion of an intestinal defect without suturing. It is described that generation
  • bioabsorbable fibers are composed of submillimeter-order fiber bundles in which single fibers are bundled, so it is difficult to completely eliminate such a coarse network structure.
  • a bioabsorbable fiber material ultrafine fibers called nanofibers have recently been studied.
  • the bioabsorbable aliphatic polyester is an electrospinning method (also called an electrostatic spinning method or an electrospinning method). It is known that biodegradable ultrafine fibers having a fiber diameter smaller than a few micrometers can be obtained by a method for producing ultrafine fibers called)).
  • Nanofibers produced by electrospinning have the advantage of being able to easily create yarns with a smaller fiber diameter than conventional molding methods.
  • the adhesion to cells and proteins is increased. Therefore, application to a carrier for cell culture and a scaffold material for regenerative medicine is being studied.
  • fine fiber molded articles obtained by electrospinning especially those made of hydrophobic aliphatic polyesters, have poor hydrophilicity, and when used in a hydrophilic environment, mutual interaction with cells and proteins. It has a problem that its action is limited, and has not been studied as a reinforcing material for biological glue.
  • the problem to be solved by the present invention is to provide a reinforcing material for biological glue that can be uniformly and easily combined with biological glue, particularly on a biological membrane. Moreover, the subject which this invention tends to solve is providing the manufacturing method of this reinforcing material for biological glue. Furthermore, the problem to be solved by the present invention is to provide an artificial biological thin film uniformly combined with biological paste.
  • the present inventors have found that a fine fiber molded body having no through-hole larger than a specific size is combined with a biological glue having excellent adhesion on a biological membrane. The inventors have found that a biological thin film can be produced, and have completed the present invention.
  • a fine fiber molded body made of a bioabsorbable polymer typified by an aliphatic polyester produced by electrospinning has a high specific surface area and high adhesion to cells and proteins. Because of its lack, it has never been studied as a reinforcing material for biological glue such as fibrin glue.
  • biological glue such as fibrin glue.
  • the present inventors have found that a fine fiber molded body made of an aliphatic polyester has high adhesiveness with a biological paste despite having low hydrophilicity, and has no through-hole.
  • a uniform artificial biological thin film can be formed, that is, a uniform regenerated tissue can be formed.
  • the present invention consists of a fiber molded body made of bioabsorbable polymer fibers having an average fiber diameter of 0.1 to 10 ⁇ m, a thickness of 10 to 150 ⁇ m, and having no through-holes of 0.01 mm 2 or more. It is a reinforcing material for biological glue. Moreover, this invention is a method of manufacturing the said reinforcing material for biological glue including the process of obtaining a fiber molded object by an electrospinning method, and the process of heat-processing this fiber molded object. Furthermore, the present invention is an artificial biological thin film comprising the biological glue reinforcing material and the biological glue, wherein at least a part of the biological glue reinforcing material is coated with the biological glue.
  • FIG. 1 is an electron micrograph of a sheet-like fiber molded body obtained in Example 2.
  • FIG. 2 is a photograph of a HE-stained specimen of a specimen obtained by autopsy after one month after placing the artificial biological membrane obtained in Example 3 on the beagle cerebrum so that the fibrin gel layer is on the brain parenchyma side.
  • FIG. 3 is a photograph of a HE-stained specimen of a specimen obtained by autopsy after one month after placing the artificial biological membrane obtained in Example 3 on a beagle cerebrum so that the fibrin gel layer is on the brain parenchyma side.
  • the fiber molded body refers to a three-dimensional molded body formed from one or a plurality of fibers by lamination, weaving, knitting, or other methods.
  • a specific preferred form of the fiber molded body for example, a non-woven fabric can be mentioned, and a tube, a mesh and the like processed based on the nonwoven fabric can be preferably used in the field of regenerative medicine, and are included in the fiber molded body in the present invention.
  • the average fiber diameter of the fibers constituting the fiber molded body is 0.1 to 10 ⁇ m. An average fiber diameter of less than 0.1 ⁇ m is not preferable because the strength of the fiber molded body cannot be maintained.
  • the average fiber diameter is larger than 10 ⁇ m, the specific surface area of the fiber is small, and the number of cells to be engrafted is not preferable. More preferably, the average fiber diameter is 0.2 to 10 ⁇ m.
  • 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. With respect to the fiber diameter in this case, the average of the length in the major axis direction and the length in the minor axis direction of the ellipse 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.
  • the fiber molded body is a fiber molded body that does not have a through hole having a surface opening area of 0.01 mm 2 or more.
  • a through-hole of 0.01 mm 2 or more when a reinforcing material and biological paste are combined on a biological membrane, a uniform composite membrane cannot be obtained by permeation of body fluid or cerebrospinal fluid, It is not preferable.
  • the penetration of body fluid and cerebrospinal fluid lowers the biopaste concentration, which is not preferable because a substitute biomembrane with sufficient strength cannot be formed.
  • tissue regeneration proceeds non-uniformly. Conventionally, webs, knits, meshes, etc.
  • bioabsorbable fibers have submillimeter order fiber bundles in which single fibers are bundled to form a net in a mesh structure, and there are submillimeter order through holes. It was difficult to eliminate the through hole.
  • the mesh portion and the through-hole portion do not have a loose and dense structure of biological paste, and tissue regeneration does not proceed unevenly.
  • tissue regeneration does not proceed unevenly.
  • the disadvantage that it is very weak against irritation such as piercing has been solved.
  • the fiber molded body used in the present invention preferably has an average surface pore area of 10 to 500 ⁇ m 2 .
  • 30 points were selected at random from photographs obtained by photographing the surface of the fiber molded body with a scanning electron microscope (Keyence Co., Ltd .: trade name “VE8800”) at a magnification of 30 to 200 times. The hole area was measured, and the average value was obtained as the average hole area.
  • the average surface opening area is smaller than 10 ⁇ m 2 , the biopaste impregnation property is insufficient, and sufficient adhesion with the biopaste cannot be obtained, which is not preferable.
  • the average surface opening area is larger than 500 ⁇ m 2, it is not preferable because sufficient strength of the fiber molded body cannot be obtained.
  • the fiber molded body used in the present invention has continuous holes from the front surface to the back surface, but is formed through a curved path, so when a composite thin film with biological glue is prepared, It does not have a sparse / dense structure and has excellent uniformity. Therefore, tissue regeneration can also proceed uniformly. Moreover, it has the characteristic that it is very strong with respect to irritation
  • the thickness of the fiber molded body used in the present invention is 10 to 150 ⁇ m. When it is smaller than 10 ⁇ m, it is not preferable because sufficient strength cannot be obtained. When it is larger than 150 ⁇ m, transparency is insufficient when it is combined with biological paste and used as an artificial biological thin film.
  • the thickness of the fiber molded body is more preferably 25 ⁇ m to 150 ⁇ m, still more preferably 50 to 150 ⁇ m.
  • the bio-glue reinforcing material comprising the fiber molded body used in the present invention is devitrified when the bio-glue is not coated, but after the bio-glue is coated and impregnated, the transparency is improved, and the artificial bio Even after covering the defect site as a thin film, the inside can be observed, and the visibility is excellent.
  • the basis weight of the fiber molded body in the present invention is preferably 1 to 30 g / m 2 . When the basis weight of the fiber molded body is less than 1 g / m 2 , it is not preferable because sufficient strength cannot be obtained.
  • the basis weight of the fiber molded body is larger than 30 g / m 2, inflammation due to the acid component decomposed from the bioabsorbable polymer is not preferable.
  • webs, knits, meshes, and the like that have been used as bioabsorbable fibers have a large basis weight, so that a large amount of decomposed inflammation-inducing components are generated.
  • the degree of inflammation is affected by the person, degradation rate, use environment, etc., it is needless to say that it is preferable that the amount of inflammation-inducing component generated is small.
  • the porosity of the fiber molded body used in the present invention is preferably 40 to 90%.
  • the bioabsorbable (or biodegradable) polymer used in the present invention is preferably an aliphatic polyester.
  • bioabsorbable polymers include polylactic acid, polyglycolic acid, polylactic acid-polyglycolic acid copolymer, polycaprolactone, polyglycerol sebacic acid, polyhydroxyalkanoic acid, polybutylene succinate, and the like. These copolymers and derivatives can be exemplified.
  • the polylactic acid copolymer has few monomer components imparting stretchability.
  • the monomer component that imparts stretchability include caprolactone monomer, ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, 1,2-butanediol, 1,4-butanediol, and polycaprolactone.
  • soft components such as diols, polyalkylene carbonate diols, and polyethylene glycol units.
  • the soft components are preferably less than 20% by weight based on the polymer. When there is more soft component than this, it becomes easy to lose self-supporting property, and it becomes a fiber molded body which is too soft and difficult to handle.
  • the monomer constituting the polymer in polylactic acid may be either L-lactic acid or D-lactic acid. There are no particular restrictions on the optical purity or molecular weight of the polymer, the composition ratio of the L-form and the D-form, and the arrangement, but a polymer having many L-forms is preferred. There is no problem using a stereocomplex of poly L lactic acid and poly D lactic acid.
  • the weight average molecular weight of the polymer is preferably 1 ⁇ 10 3 to 5 ⁇ 10 6 , more preferably 1 ⁇ 10 4 to 1 ⁇ 10 6 , and further preferably 5 ⁇ 10 4 to 5 ⁇ 10 5 . is there. Further, the terminal structure of the polymer and the catalyst for polymerizing the polymer can be arbitrarily selected. When the weight average molecular weight of the polymer is smaller than 1 ⁇ 10 3 , the strength of the obtained fiber molded body is insufficient, and it is not preferable because a thin sheet is hardly obtained.
  • the weight average molecular weight of the polymer is larger than 5 ⁇ 10 6 , it is not preferable because the viscosity of the polymer solution becomes high and the moldability becomes poor when a fiber molded body is obtained.
  • the fiber molded body used in the present invention may be used in combination with other polymers and other compounds as long as the purpose is not impaired.
  • the polymer preferably has a high purity.
  • the amount of residues such as additives, plasticizers, residual catalysts, residual monomers, and residual solvents used in molding and post-processing is small.
  • the biopaste in the present invention is not particularly limited, but among the adhesives excellent in biocompatibility used for surgery and the like, particularly the adhesive that is converted into fibroblasts over time in vivo. Is preferably used. Such biopaste preferably exhibits adhesive ability by a rapid biochemical reaction by mixing a plurality of components. For this reason, biopaste is generally known as a combination of a biopaste precursor and a specific additional component that chemically converts it into biopaste.
  • the biopaste precursor is a pre-stage of biochemical reaction in the biopaste as described above, and does not have an adhesive ability by itself.
  • the biological paste used in the present invention is not particularly limited as long as it meets the above definition.
  • it is at least one selected from the group consisting of fibrin glue, gelatin adhesive, cellulose preparation, collagen adhesive, chitosan adhesive, alginic acid preparation, etc., or a mixture of two or more of these. Is preferred.
  • fibrin glue or gelatin-based adhesive is preferred, and fibrin glue is more preferred from the applicability of the artificial biological thin film provided by the present invention.
  • the fibrin glue used in the present invention include fibrinogen lyophilized powder, fibrinogen lyophilized powder, fibrinogen lysate, thrombin lyophilized powder, and thrombin lysate which are precursors of fibrin glue.
  • Fibrin glue is a physiological tissue adhesive that utilizes the final stage of blood coagulation, and fibrinogen contained in it becomes a soluble fibrin clot by the action of thrombin, and blood coagulation factor XIII activated by thrombin in the presence of calcium ions To form a stable insoluble urea fibrin clot with physical strength and adhere and close the tissue.
  • fibrin clot for example, fibroblasts proliferate, collagen fibers and granulation matrix components are produced, and are cured through tissue repair.
  • fibrin glue examples include Bolheel (registered trademark: manufactured by Chemical and Serum Therapy Research Institute), Veriplast (registered trademark: manufactured by CSL Behring), and the like.
  • the fiber molded body used in the present invention may further contain a second component other than the bioabsorbable polymer.
  • the components include, for example, FGF (fibroblast growth factor), EGF (epidermal growth factor), PDGF (platelet-derived growth factor), TGF- ⁇ ( ⁇ -type transforming growth factor), NGF (nerve growth factor), HGF Cell growth factors such as (hepatocyte growth factor) and BMP (bone formation factor) can be mentioned.
  • the fibers of the fiber molded body are made of long fibers.
  • long fiber refers to a fiber molded body that is formed without adding a fiber cutting step in the process from spinning to processing into a fiber molded body.
  • Electrospinning method and spunbonding method It can be formed by a melt blow method or the like. Of these, the electrospinning method is preferably used.
  • the electrospinning method is the same in principle as a method called an electrostatic spinning method or an electrospray method, and these are also included in the electrospinning method referred to in the present invention.
  • the electrospinning method is a method of obtaining a fiber molded body on an electrode by applying a high voltage to a solution in which a polymer is dissolved in a solvent.
  • the steps include a step of producing a solution by dissolving a polymer in a solvent, a step of applying a high voltage to the solution, a step of ejecting the solution, and evaporating the solvent from the ejected solution to form a fiber molded body.
  • the step of producing a solution by dissolving a polymer in a solvent in the electrospinning method will be described.
  • the concentration of the bioabsorbable polymer with respect to the solvent in the solution is preferably 1 to 30% by weight. If the concentration of the bioabsorbable polymer is less than 1% by weight, it is not preferable because the concentration is too low, making it difficult to form a fiber molded body. On the other hand, if it is larger than 30% by weight, the fiber diameter of the resulting fiber molded body is undesirably large.
  • the concentration of the bioabsorbable polymer with respect to the solvent in the solution is more preferably 2 to 20% by weight.
  • a solvent may be used individually by 1 type and may be used combining several solvent.
  • the solvent is not particularly limited as long as it can dissolve the bioabsorbable polymer and can evaporate at the spinning stage to form a fiber.
  • solvent mixtures of include solvent mixtures of.
  • dichloromethane and ethanol are preferably used in view of handling properties and physical properties.
  • a step of applying a high voltage to the solution, a step of ejecting the solution, and a step of evaporating the solvent from the ejected solution to form a fiber molded body will be described.
  • the method of applying a voltage is not particularly limited as long as the solution in which the bioabsorbable polymer is dissolved is ejected and a fiber molded body is formed, but the method of inserting the electrode into the solution and applying the voltage, There is a method of applying a voltage to the solution ejection nozzle.
  • An auxiliary electrode can be provided separately from the electrode applied to the solution.
  • the value of the applied voltage is not particularly limited as long as the fiber molded body is formed, but a range of 5 to 50 kV is usually preferable.
  • the applied voltage is less than 5 kV, it is not preferable because the fiber molded body is not easily formed without jetting the solution, and when the applied voltage is more than 50 kV, discharge tends to occur from the electrode toward the ground electrode. More preferably, it is in the range of 6 to 30 kV.
  • the desired potential may be generated by any appropriate method known in the art.
  • the solvent used is volatilized to form a fiber molded body. Ordinary spinning is performed at room temperature in the atmosphere, but when volatilization is insufficient, it can be performed under negative pressure or in a high-temperature atmosphere.
  • the spinning temperature depends on the evaporation behavior of the solvent and the viscosity of the spinning solution, but is usually in the range of 0 to 50 ° C.
  • a preferable method is a method for eliminating the electric charge with an ionizer.
  • An ionizer is an apparatus that can generate ions by a built-in ion generator and discharge the charges to the charged object, thereby eliminating the charge of the charged object.
  • a preferable ion generator that constitutes an ionizer used in the method for producing a fiber molded body in the present invention there is an apparatus that generates ions by applying a high voltage to a built-in discharge needle.
  • the step of accumulating the fiber molded body due to the charge disappearance will be described.
  • the method for accumulating the fiber molded body by the charge disappearance is not particularly limited, but as a normal method, there is a method in which the electrostatic force of the fiber molded body is lost by the charge disappearance and dropped and accumulated by its own weight.
  • a method for producing a fiber having a smooth fiber surface it can be produced by setting the atmosphere during spinning to low humidity. Preferably it is 25% or less, More preferably, it is 20% or less.
  • the method of treating the fiber molded body by heat treatment is not particularly limited, and examples thereof include heating by contact using a hot plate and a hot roll, in addition to hot air heating, vacuum heating, infrared heating, and microwave heating.
  • the heat treatment can also be performed in an inert gas atmosphere such as nitrogen or argon.
  • an inert gas atmosphere such as nitrogen or argon.
  • it does not restrict
  • the fiber molded body used in the present invention is a fiber molded body in which a cotton-like fiber structure is further laminated on the surface or the cotton-like structure is used in the present invention as long as the object of the present invention is not impaired.
  • coating treatment for imparting antithrombogenicity and surface coating with an antibody or a physiologically active substance can be optionally performed.
  • 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 molded body 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.
  • the drug may be a protein preparation or a nucleic acid drug as long as it can maintain activity in a volatile solvent.
  • medical agent for example, a metal, polysaccharide, a fatty acid, surfactant, and a volatile solvent tolerance microbe, may be included.
  • the artificial biological thin film which consists of the said reinforcing material for biological glues and biological glue, and at least one part of the reinforcing material for biological pastes is coat
  • ⁇ density of the fiber molded body
  • ⁇ 0 density of the bioabsorbable polymer in the bulk state
  • Contact angle measurement was measured 5 times using 7% albumin (derived from bovine serum, pH 5.2: manufactured by Wako Pure Chemical Industries) / PBS (200112 Phosphate-Buffer Salines (PBS), liquid: manufactured by GIBCO). The average value was calculated. 7).
  • the inner diameter of the ejection nozzle was 0.8 mm, the voltage was 8 kV, and the distance from the ejection nozzle to the flat plate was 25 cm.
  • the flat plate was used as a cathode during spinning.
  • the obtained fiber molded body was heat-treated at 70 ° C. for 10 minutes.
  • the obtained fiber molded body had an average fiber diameter of 4.5 ⁇ m, a thickness of 100 ⁇ m, a basis weight of 16.2 g / m 2 , and a porosity of 87.6%. No through-hole of 0.01 mm 2 or more was observed, and the average surface opening area was 31.7 ⁇ m 2 .
  • the contact angle of the 7% albumin solution on the surface of the fiber molded body is 120 degrees, which is poor in hydrophilicity, that is, when forming a composite thin film of the fiber molded body and the biological glue on the biological membrane, the fiber molding is performed. It was found that the penetration of body fluid and cerebrospinal fluid into the body was low.
  • the fiber molded body was installed as described in the section of “7. Pressure resistance test”.
  • the obtained fiber molded body was improved in transparency by permeation of fibrin glue, and the inside could be observed. Subsequently, pressure was applied from the outside, and the internal pressure when the membrane broke was measured. As a result, the pressure when the film burst was 32,460 Pa. From the above, even if a microfiber molded body with poor hydrophilicity is used as a reinforcing material for a composite thin film with biological glue, it exhibits sufficient adhesiveness and pressure resistance required for artificial biological membrane materials. all right. Further, when the obtained composite thin film was pierced with the tip of the tweezers, the through hole was not opened.
  • Example 2 A homogeneous solution was prepared by dissolving 8.5 parts by weight of a lactic acid-glycolic acid copolymer (weight average molecular weight 204,000, manufactured by Purac) with 85 parts by weight of a dichloromethane solution and 5 parts by weight of an ethanol solution. Spinning was performed by electrospinning to obtain a sheet-like fiber molded body. The inner diameter of the ejection nozzle was 0.8 mm, the voltage was 8 kV, and the distance from the ejection nozzle to the flat plate was 25 cm. The flat plate was used as a cathode during spinning. The obtained fiber molded body was heat-treated at 70 ° C. for 10 minutes.
  • the obtained fiber molded body had an average fiber diameter of 4.6 ⁇ m, a thickness of 80 ⁇ m, a basis weight of 13.8 g / m 2 , and a porosity of 86.7%. No through-hole of 0.01 mm 2 or more was observed, and the average surface opening area was 134.5 ⁇ m 2 . Further, 1 ⁇ L of the 7% albumin solution was put on the obtained fiber molded body, and the change of the droplets was observed. As a result, it was confirmed that the liquid droplets did not enter the inside of the fiber molded body and had a hydrophobic surface.
  • the contact angle of the 7% albumin solution on the surface of the fiber molded body is 123 degrees, and the hydrophilicity is poor, that is, when forming a composite thin film of the fiber molded body and the biological glue on the biological membrane, the fiber molding is performed. It was found that the penetration of body fluid and cerebrospinal fluid into the body was low. Rabbit skin is collected as a living tissue, and the prepared fiber molded body is placed on the hole (5mm ⁇ ) in the center of the rabbit skin so that the hole is blocked, and fibrin glue (Bolheel (registered trademark)) is placed from above. ). At this time, the obtained fiber molded body was improved in transparency by permeation of fibrin glue, and the inside could be observed.
  • Neobale registered trademark
  • NV-M-015G manufactured by Gunze Co., Ltd., thickness 0.15 mm
  • Neobale registered trademark
  • NV-M-015G manufactured by Gunze Co., Ltd., thickness 0.15 mm
  • Neobale had an average fiber diameter of 20 ⁇ m and a fiber bundle (146 ⁇ m) in which single fibers were bundled to have a network structure.
  • a through-hole of 0.01 mm 2 or more was observed, and the average surface opening area was 0.34 mm 2 .
  • the thickness was 190 ⁇ m
  • the basis weight was 32.6 g / m 2
  • porosity was 88.6%.
  • Example 1 As a result of Example 1, it is superior in hydrophilicity, that is, when producing a composite thin film of a fiber molded body and a biological paste on a biological membrane, the permeability of body fluid and cerebrospinal fluid into the fiber molded body is I found it expensive. As a result of the pressure test, the pressure when the composite membrane broke was 26,730 Pa. Moreover, when the obtained composite thin film was stabbed with the tip of the tweezers, a through hole was opened.
  • bicyclyl mesh knit (registered trademark, manufactured by Johnson & Johnson Co., Ltd.), which is a mesh made of polyglactin 910, was used.
  • the bifilar mesh knit had an average fiber diameter of 15.2 ⁇ m, and had a network structure of fiber bundles (126 ⁇ m) in which single fibers were bundled.
  • the thickness was 196 ⁇ m, the basis weight was 67.0 g / m 2 , and the porosity was 70.7%.
  • 1 ⁇ L of the 7% albumin solution was put on bicyclyl mesh knit, and changes in the droplets were observed.
  • Example 3 As the fiber molded body, Dexon mesh # 4 (registered trademark, manufactured by Davis & Geck Co., Ltd.), which is a polyglycolic acid-based mesh, was used.
  • the average fiber diameter of Dexon Mesh # 4 was 13.6 ⁇ m, and it had a network structure with a fiber bundle (187 ⁇ m) in which single fibers were bundled. A through-hole of 0.01 mm 2 or more was observed, and the average surface opening area was 0.013 mm 2 .
  • the thickness was 205 ⁇ m, the basis weight was 56.0 g / m 2 , and the porosity was 82.1%.
  • 1 ⁇ L of the above 7% albumin solution was added onto Dexon mesh # 4, and changes in the droplets were observed. As a result, the liquid droplets quickly penetrated into the fiber molded body, making it difficult to measure the contact angle. Therefore, it was confirmed that the surface was hydrophilic compared to Example 1.
  • Example 3 Bolheel (registered trademark), which is a commercially available biological tissue adhesive, was used to produce an artificial biological membrane for implantation in a living body.
  • the fiber molded body described in Example 1 was cut into a size of 2 cm ⁇ 2 cm (4 cm 2 ) and placed in a 10 cm plastic petri dish.
  • a 1 cm ⁇ 1 cm (1 cm 2 ) hole was formed in the center of a transparent plastic film having a size of 3 cm ⁇ 3 cm (9 cm 2 ), and the plastic film was placed on the fiber molded body.
  • 3 mL of a solution containing aprotinin (3000KIE) was added to a vial containing 240 mg of lyophilized fibrinogen in Bolheal and factor XIII 225 units and mixed to make 3 mL of fibrinogen solution, about 0.2 mL of fibrinogen solution Inhaled into a spray syringe.
  • Thrombin (750 units) powder was dissolved in 3 mL of a solution containing 17.7 mg of calcium chloride, 0.2 mL of which was drawn into a 1 mL syringe. Each syringe was attached to a Bolheel spray set (Akita Sumitomo Bake Co., Ltd.). Using this spray set, 0.2 mL of each fibrinogen solution and thrombin solution was sprayed evenly from the top of the plastic film overlaid on the fiber molded body.
  • the reinforcing material for biological glue of the present invention is excellent in adhesiveness with biological glue and can form a uniform composite thin film. Therefore, the artificial biofilm composed of the biopaste reinforcing material and the biopaste of the present invention is used as an artificial substitute dura mater, anti-adhesion material, as a medical article, particularly as a protective material, covering material, or seal material for an organ surface or a wound site, It is preferably used as a hemostatic material.

Abstract

L'invention divulgue un matériau de renforcement pour une colle biologique, qui peut être composé avec une colle biologique de façon homogène et simple sur une membrane biologique. L'invention divulgue de façon spécifique un matériau de renforcement pour une colle biologique, qui comprend un matériau en fibre moulé, le matériau en fibre moulé comprenant des fibres composées d'un polymère bio-absorbable et qui présentent un diamètre de fibre moyen compris entre 0,1 µm et 10 μm, ayant une épaisseur comprise entre 10 µm et 150 μm, et ne comportant aucun trou de passage dont la taille est égale ou supérieure à 0,01 mm2; un procédé de production du matériau de renforcement par une technique de filage électrostatique; et un film biologique artificiel mince comprenant le matériau de renforcement et un composant qui constitue une colle biologique.
PCT/JP2011/061008 2010-05-07 2011-05-06 Matériau de renforcement pour une colle biologique, et procédé de production de celui-ci WO2011138974A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014083106A (ja) * 2012-10-19 2014-05-12 Gunze Ltd 生体吸収性組織補強材
JPWO2013172468A1 (ja) * 2012-05-14 2016-01-12 帝人株式会社 滅菌組成物

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004087012A1 (fr) * 2003-03-31 2004-10-14 Teijin Limited Composite forme d'un substrat de support et de collagene, procede de production du substrat de support et du composite
JP2004321484A (ja) * 2003-04-24 2004-11-18 Sangaku Renkei Kiko Kyushu:Kk 医療用高分子ナノ・マイクロファイバー
JP2005290610A (ja) * 2004-03-31 2005-10-20 Akihiko Tanioka 多糖類のナノスケールの繊維および成形体
WO2005113030A1 (fr) * 2004-05-21 2005-12-01 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Préparation de collage de tissu
WO2007063820A1 (fr) * 2005-12-02 2007-06-07 Sunstar Suisse Sa Matériel biocompatible ayant une structure biocompatible non tissée de nano- ou de micro-fibres, produit par une méthode d’électrofilage, et méthode pour produire le matériel
JP2009089859A (ja) * 2007-10-05 2009-04-30 Idemitsu Technofine Co Ltd 創傷被覆材
JP2009089837A (ja) * 2007-10-05 2009-04-30 Idemitsu Technofine Co Ltd 創傷被覆材
JP2010069031A (ja) * 2008-09-19 2010-04-02 Chemo Sero Therapeut Res Inst シート状フィブリン糊接着剤
JP2010246750A (ja) * 2009-04-16 2010-11-04 Teijin Ltd 創傷治療材料

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004087012A1 (fr) * 2003-03-31 2004-10-14 Teijin Limited Composite forme d'un substrat de support et de collagene, procede de production du substrat de support et du composite
JP2004321484A (ja) * 2003-04-24 2004-11-18 Sangaku Renkei Kiko Kyushu:Kk 医療用高分子ナノ・マイクロファイバー
JP2005290610A (ja) * 2004-03-31 2005-10-20 Akihiko Tanioka 多糖類のナノスケールの繊維および成形体
WO2005113030A1 (fr) * 2004-05-21 2005-12-01 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute Préparation de collage de tissu
WO2007063820A1 (fr) * 2005-12-02 2007-06-07 Sunstar Suisse Sa Matériel biocompatible ayant une structure biocompatible non tissée de nano- ou de micro-fibres, produit par une méthode d’électrofilage, et méthode pour produire le matériel
JP2009089859A (ja) * 2007-10-05 2009-04-30 Idemitsu Technofine Co Ltd 創傷被覆材
JP2009089837A (ja) * 2007-10-05 2009-04-30 Idemitsu Technofine Co Ltd 創傷被覆材
JP2010069031A (ja) * 2008-09-19 2010-04-02 Chemo Sero Therapeut Res Inst シート状フィブリン糊接着剤
JP2010246750A (ja) * 2009-04-16 2010-11-04 Teijin Ltd 創傷治療材料

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2013172468A1 (ja) * 2012-05-14 2016-01-12 帝人株式会社 滅菌組成物
JP2014083106A (ja) * 2012-10-19 2014-05-12 Gunze Ltd 生体吸収性組織補強材

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