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WO2021045177A1 - Matériau prothétique médical - Google Patents

Matériau prothétique médical Download PDF

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Publication number
WO2021045177A1
WO2021045177A1 PCT/JP2020/033524 JP2020033524W WO2021045177A1 WO 2021045177 A1 WO2021045177 A1 WO 2021045177A1 JP 2020033524 W JP2020033524 W JP 2020033524W WO 2021045177 A1 WO2021045177 A1 WO 2021045177A1
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WIPO (PCT)
Prior art keywords
lactide
base material
caprolactone
porous
layer
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Ceased
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PCT/JP2020/033524
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English (en)
Japanese (ja)
Inventor
西原愛美
井手純一
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JMS Co Ltd
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JMS Co Ltd
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Filing date
Publication date
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Publication of WO2021045177A1 publication Critical patent/WO2021045177A1/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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body

Definitions

  • the present invention relates to a medical prosthetic material and a method for producing the same.
  • prosthetic material When a part of a body tissue or organ is lost due to a disease or a wound, surgical treatment is performed to supplement the morphology and function of that part with an artificial object.
  • the artificial material used at that time is called a prosthetic material, and alternative prosthetic materials of various tissues are used clinically.
  • prosthesis human or animal organs and organs, biological materials such as collagen and gelatin, and artificial materials such as metals, ceramics and resins are used.
  • biological materials have a risk of heat generation and delayed tissue repair due to infection or foreign body reaction
  • prosthetic materials made of artificial materials have been commercialized.
  • Prosthetic materials made of artificial materials have excellent durability and workability.
  • non-absorbable synthetic polymers such as polyester and polypropylene can be processed into knitted or mesh shapes to achieve the desired strength and soft tissues of living organisms. It is used as a material for prosthetic materials with flexible physical properties that are suitable for organs and organs.
  • prosthetic materials for soft tissues are required to have flexible and high-strength physical properties from the viewpoint of familiarity with living tissues and handleability during surgery.
  • a material for a prosthetic material a material obtained by forming a synthetic polymer material having excellent biocompatibility into a porous body having high porosity or porosity is used.
  • the porous body include sponges, meshes, knitted fabrics, woven fabrics, and the like having holes penetrating in the thickness direction or interfiber voids.
  • Hernia is a defect in the soft tissue of the abdominal wall, and is a symptom in which organs and tissues in the abdominal cavity press against the fragile abdominal wall and protrude.
  • repair surgery is performed by inserting a prosthesis into the abdominal wall to increase the strength of the abdominal wall.
  • a commonly used prosthesis for the repair surgery is a mesh made from polypropylene fibers. While this mesh requires strength to reinforce the tissue, its high rigidity stimulates the surrounding tissue of the implanted prosthesis (eg, peritoneum, fascia, skin, etc.) and is excessive. Since there are drawbacks such as causing inflammation and hindering the movement of the affected area, flexibility is required so as to be familiar with the surrounding tissue and not to give excessive irritation. Therefore, a highly flexible high-strength mesh with devised filament diameter and weaving density has been commercialized.
  • ePTFE obtained by high-speed stretching of polyester fiber knitting as a material for a large-diameter artificial blood vessel having an inner diameter of 10 mm or more and polytetrafluoroethylene (PTFE) as a material for a medium-diameter artificial blood vessel having an inner diameter of 8 mm or less.
  • PTFE polytetrafluoroethylene
  • a porous body made of a thermoplastic resin having excellent biocompatibility is widely used clinically as a material for a prosthetic material for soft tissues.
  • the medium-diameter artificial blood vessel made of ePTFE porous body also has a porous structure with many finer pores, so it has plasma permeability and forms seroma after transplantation.
  • the disadvantage is that edema is likely to appear.
  • Non-Patent Document 1 discloses a technique of coating an artificial blood vessel with an absorbent material as a means for preventing blood leakage from the artificial blood vessel after transplantation.
  • Patent Document 1 discloses a prosthetic material for living organs in which a non-permeable layer containing an absorbent material is provided on the inner surface of a porous artificial blood vessel such as a polyester knit.
  • a porous artificial blood vessel such as a polyester knit.
  • the absorbent material a mixture of absorbent polyester or absorbent polyester such as polylactic acid, polyglycolic acid, polyhydroxybutyrate, polyhydroshikivaleric acid, poly ⁇ -caprolactone, polyethylene adipate or a copolymer thereof is disclosed. It is disclosed that the absorbent material is fixedly laminated on the inner peripheral surface of an artificial blood vessel by a method such as adhesion or dipping using a good solvent of the absorbent material.
  • a hernia treatment prosthesis in which an absorbent collagen film or an absorbent resin film is laminated on a polypropylene mesh in order to reduce adhesion between the affected organ and the prosthesis during the period from surgery to the regeneration of the peritoneal lining layer.
  • the material has been commercialized.
  • Physiomesh registered trademark
  • caprolactone / glycolide copolymer film which is an absorbent polymer material, is laminated on both sides of the propylene mesh. .. Since this film is rigid and has strong tension, there is a risk that bending it will cause physical stress on the surrounding tissue and insufficient healing, and a laminate that does not impair the flexibility of the polypropylene mesh is also desired.
  • the present invention provides for body fluid leakage and in a medical prosthetic material comprising a non-absorbable porous substrate layer and a non-permeable resin layer that is fixed to the porous substrate layer and contains an absorbent material. It is an object of the present invention to provide a medical prosthetic material capable of achieving both a barrier property of appropriately preventing infiltration of living tissue and flexibility suitable for living tissue.
  • One aspect of the present invention includes a non-absorbable porous base material layer and a non-permeable resin layer fixed to the porous base material layer and containing an absorbent material, wherein the absorbent material is lactide. It relates to a medical prosthesis, which is a copolymer having a caprolactone molar ratio (lactide: caprolactone) of 65:35 to 80:20.
  • Another aspect of the present invention is a method for producing a medical prosthesis, which comprises a non-absorbable porous base material layer and a non-permeable resin layer fixed to the porous base material layer and containing an absorbent material.
  • the absorbent material has a molar ratio of lactide to caprolactone (lactide: caprolactone).
  • the present invention relates to a method for producing a medical prosthesis, which is a copolymer of 65:35 to 80:20.
  • a medical prosthetic material having both a barrier property of appropriately preventing body fluid leakage and infiltration of living tissue and flexibility suitable for living tissue.
  • FIG. 1 is a schematic cross-sectional view of an example of the medical prosthesis material of the present invention.
  • FIG. 2 is a schematic partial cross-sectional view of another example of the medical prosthesis material of the present invention.
  • porous base material layer constituting the medical prosthesis material of the present invention (hereinafter, “medical prosthesis material” may be abbreviated as “prosthesis material”) is referred to as “base material layer”. (Sometimes abbreviated as), which has the flexibility to adapt to living tissue in a state where the resin layer is not fixed. Since the base material layer has a small gap (difference) in physical properties such as hardness and elongation from the living tissue, it has flexibility suitable for the living tissue.
  • a non-permeable resin layer containing an absorbent material having a specific composition is fixed to the surface of the base material layer, it is possible to appropriately prevent the leakage of body fluids and the infiltration of biological tissues (barrier property).
  • carrier property it may be abbreviated as “appropriate barrier property”) and based on a new finding that it is possible to suppress the decrease in flexibility of the base material layer due to the adhesion of the resin layer.
  • Ensuring flexibility that is compatible with living tissue means that the adhesion of the resin layer has little effect on the originally highly flexible base material layer, and the flexibility of the base material layer itself and the flexibility of the prosthetic material. Means that the difference between them is small.
  • the flexibility of the prosthesis can be evaluated, for example, by the flexural rigidity, and the flexural rigidity can be measured by the method described in the examples.
  • one aspect of the present invention includes a non-absorbable porous base material layer and a non-permeable resin layer fixed to the porous base material layer and containing an absorbent material, and the absorbent material comprises.
  • a medical prosthesis which is a copolymer having a molar ratio of lactide to caprolactone (lactide: caprolactone) of 65:35 to 80:20.
  • lactide: caprolactone lactide: caprolactone
  • non-absorbable means that the individual remains in the living body during the period in which the individual can survive in the implanted living body.
  • "absorbent” means a state in which the resin layer collapses (cracks, holes, etc. are damaged after a predetermined period of time has passed after being implanted in the living body, and the shape cannot be maintained when an external force is applied. ), which means that the collapse occurs preferably within a period of 3 weeks or more and 3 months or less.
  • the above-mentioned predetermined period from the burial to the start of collapse may be referred to as a shape retention period.
  • impermeable refers to a state in which water is substantially impervious to the maximum blood pressure, and specifically, the amount of water permeation under a water pressure of 120 mmHg (16 kPa) is 0.1 mL / cm. It is 2 / min or less, and the preferable water permeation amount is 0 mL / cm 2 / min.
  • water permeability means that the water permeation amount is larger than 0.1 mL / cm 2 / min, and the preferable water permeation amount is 10 mL / cm 2 / min or more.
  • porous refers to a structure including a large number of pores or interfiber voids communicating from one main surface of the base material layer to the other main surface.
  • FIG. 1 is a schematic cross-sectional view of an example of a sheet-shaped medical prosthesis material of the present invention, and the sheet-shaped medical prosthesis material 1 is fixed to a porous base material layer 2 and a porous base material layer 2. Includes the resin layer 3.
  • FIG. 2 is a schematic partial cross-sectional view of an example of the tubular medical prosthesis material of the present invention, and the tubular medical prosthesis material 4 is formed on a porous base material layer 5 and a porous base material layer 5. Includes the fixed resin layer 6.
  • the base material layers 2 and 5 are made of a non-absorbable material formed into a predetermined shape according to the use of the prosthesis material, and have water permeability that allows water to permeate in the thickness direction.
  • Examples of the base material layers 2 and 5 include a sheet-like material and a tubular material.
  • the base material layer 2 shown in FIG. 1 is a sheet-like material
  • the base material layer 5 shown in FIG. 2 is a tubular material. Since the base material layer 5 is tubular, it has a hollow portion 7 inside.
  • the non-absorbable material Since the non-absorbable material remains in the living body during the period in which the individual can survive in the implanted living body, it is desirable that the non-absorbable material is a non-absorbable synthetic polymer material having excellent biocompatibility.
  • the base material layer can be produced by the same material and processing technique as the conventionally known prosthetic material.
  • Preferred non-absorbent materials include polyethylene, polypropylene, polyester, nylon, polytetrafluoroethylene, and combinations thereof.
  • a mesh, a woven fabric, a knitted fabric, a non-woven fabric, a braid (braided cord) made by braiding or weaving fibers, a sponge made by foaming or pore-forming technology, or a resin is stretched.
  • a porous body porous body such as a porous body in which voids are created by tearing the fabric.
  • the form of the fiber may be any form such as a spun yarn, a multifilament yarn, a monofilament yarn, and a film split fiber yarn.
  • the pores or interfiber voids of the base material layer provide a space or scaffold for autologous tissue to invade and promote tissue regeneration after implantation of the prosthesis material.
  • the diameter of the pores or the length of the interfiber gap may be appropriately selected depending on the intended use.
  • the prosthetic material of the present invention is a prosthetic material used for hernia treatment, it is used for conventional hernia treatment. It may be equivalent to that of a tissue repair prosthetic material, and when the prosthetic material of the present invention is an artificial blood vessel, it may be equivalent to that of a conventionally known artificial blood vessel.
  • the base material layers 2 and 5 have the strength to supplement the defective tissue of the affected area and have the flexibility to be compatible with the living tissue.
  • the thickness of the base material layers 2 and 5 is generally in the range of 50 to 700 ⁇ m.
  • Examples of the materials for the base material layers 2 and 5 include a commercially available hernia repair batch (for example, Prolean (registered trademark) mesh (manufactured by Ethicon), Paritex TM mesh (manufactured by Sofradim Production), and bird mesh (manufactured by CR Bird).
  • a commercially available hernia repair batch for example, Prolean (registered trademark) mesh (manufactured by Ethicon), Paritex TM mesh (manufactured by Sofradim Production), and bird mesh (manufactured by CR Bird).
  • Polyester fiber artificial blood vessel for example, Zelsoft (registered trademark) (Basque Tech Limited), JGraft (registered trademark) (Nippon Lifeline Co., Ltd.), HEMAGARD (registered trademark) (MAQUET)), ePTFE Used in artificial blood vessels (for example, Goretex (registered trademark) graft (manufactured by Nippon Gore Co., Ltd.), ADVANTA (registered trademark) PTFE (manufactured by Ethicon Medical Corporation), Hilex Graft (manufactured by Hilex Corporation)) You can use the materials that are available.
  • Zelsoft registered trademark
  • JGraft registered trademark
  • HEMAGARD registered trademark
  • MAQUET HEMAGARD
  • ePTFE Used in artificial blood vessels for example, Goretex (registered trademark) graft (manufactured by Nippon Gore Co., Ltd.), ADVANTA (registered trademark) PTFE (manufactured by Ethicon Medical Corporation
  • the resin layers 3 and 6 are impermeable layers formed of an absorbent material.
  • the resin layers 3 and 6 may be fixed to only one main surface of the pair of main surfaces of the base material layers 2 and 5, but may be fixed to both main surfaces.
  • the resin layer is preferably fixed to only one of the pair of main surfaces of the base material layers 2 and 5 from the viewpoint of achieving both appropriate barrier properties and flexibility suitable for living tissue.
  • the resin layers 3 and 6 are fixed to only one main surface of the base material layers 2 and 5, and in the example shown in FIG. 2, the resin layer 6 is a cylinder. It is fixed to the outer peripheral surface of the shaped base material layer 5.
  • the resin layers 3 and 6 collapse after a lapse of a predetermined period and cannot perform their functions.
  • the resin layers 3 and 6 permeate the living tissue including body fluids such as blood and cells within a predetermined period, preferably 3 weeks or more, and 3 months or less. Block. If the resin layers 3 and 6 collapse too quickly, there is a high risk of adverse events such as blood leakage and adhesion to surrounding tissues. If the disintegration is too slow, adverse effects may occur by blocking bioactive substances and signal transduction between normal tissues for a long period of time.
  • the presence or absence of an appropriate barrier property can be evaluated by the value of the water permeation amount, and the water permeation amount can be obtained by the method described in Examples. If the water permeability measured by this method is 0.1 mL / cm 2 / min or less, it can be evaluated that there is an appropriate barrier property against body fluids and living tissues.
  • Examples of the absorbent material include copolymers having a molar ratio of lactide and caprolactone of 65:35 to 80:20 from the viewpoint of achieving both appropriate barrier properties and flexibility suitable for living tissues.
  • the molar ratio can be measured by the method described in Examples.
  • Table 1 below shows the physical characteristics of the absorbent material investigated or measured by the inventors.
  • the glass transition temperature is the temperature at which the resin changes from a flexible rubber state to a hard solidified state, and the resin softens in an environment higher than the glass transition temperature. Therefore, a resin having a glass transition temperature lower than the human body temperature is preferable as an absorbent material in the present invention because it exhibits rubber-like flexibility in the body.
  • the glass transition temperature can be measured by the following method.
  • a differential scanning calorimetry (DSC) is used to obtain the DSC curves for heating and cooling the resin.
  • the glass transition temperature is measured as the baseline shift position that appears on the lower temperature side than the melting and crystallization peaks.
  • Elastic modulus is a physical property value that indicates the difficulty of deformation of a material and is measured by a tensile test. The smaller the elastic modulus, the more flexible and easily deformable the material is, and in the present invention, the smaller this value is, the more preferable the material. From Table 1, when the copolymer molar ratio (lactide: caprolactone) of L-lactide and ⁇ -caprolactone is 70:30, the elastic modulus (Young's modulus) is significantly lower than that of other absorbent materials, and excellent flexibility is achieved. It can be seen that it has sex.
  • the "shape retention period" in Table 1 can be evaluated by the following method.
  • the resin layers 3 and 6 disintegrate in vivo within a period of 3 weeks or more and 3 months or less after implantation. Synthetic polymer materials are preferred.
  • the shape retention period is measured in in vivo or in vitro tests.
  • In vivo a sample is implanted subcutaneously or intramuscularly in an animal, taken out after a certain period of time, and shape observation and tensile test are performed.
  • the test method for the in vitro test is shown in ISO15814.
  • the sample is immersed in a phosphate buffer solution adjusted to pH 7.4, which simulates the in vivo environment, and sterile incubation under a temperature condition of 37 ⁇ 1 ° C. It can be evaluated by shape observation or tensile test after a lapse of a predetermined period. Table 1 shows the period during which no cracks or damages such as holes are visually confirmed as the shape retention period as the shape retention period.
  • the present inventors have an appropriate barrier property if the copolymer has a molar ratio of lactide to caprolactone (lactide: caprolactone) of 65:35 to 80:20. It was found that it is possible to achieve both flexibility and flexibility suitable for living tissue.
  • the molar ratio of the copolymer is not preferable when the molar ratio of lactide is smaller than 65% because it collapses in vivo before 3 weeks from implantation. On the other hand, when the molar ratio of lactide is larger, the elastic modulus is increased and the flexibility is lost.
  • the molar ratio of the copolymer, which is the material of the resin layers 3 and 6, is 65:35 to 80:20, preferably 65: from the viewpoint of achieving both appropriate barrier properties and flexibility suitable for living tissues. It is 35 to 75:25, more preferably 67:33 to 75:25, and even more preferably 70:30.
  • the weight average molecular weight of the copolymer is preferably 100,000 or more and 1 million or less from the viewpoint of moldability.
  • the weight average molecular weight of the copolymer can be measured by the method described in Examples.
  • the copolymer in the present invention may be either a random polymer or a block polymer, but a random polymer is preferable from the viewpoint of flexibility.
  • a random polymer is preferable from the viewpoint of flexibility.
  • the copolymer as long as the molar ratio is satisfied, two or more kinds of copolymers having different molar ratios can be mixed and used.
  • the resin layers 3 and 6 in the present invention may contain only the copolymer having the above molar ratio, or may further contain other polymers and copolymers as long as they do not affect the present invention. Good.
  • the method for preparing the copolymer in the present invention is not particularly limited, and conventionally known methods can be used.
  • lactide and caprolactone may be used as starting materials and copolymerized by ring-opening polymerization, or lactide (cyclic dimer of lactic acid) is synthesized from lactic acid and co-polymerized with caprolactone. It may be polymerized.
  • the polymerization temperature of lactide and caprolactone is not particularly limited, but is preferably 100 to 170 ° C. because the obtained film has excellent flexibility.
  • the method for synthesizing lactide using lactic acid is not particularly limited, and a conventionally known method can be used.
  • the lactide is not particularly limited, and L-lactide, D-lactide and a mixture thereof (D, L-lactide) can be used, and the lactic acid is L-lactic acid, D-lactic acid, and a mixture thereof (Lactic acid). D, L-lactic acid) can be used.
  • D, L-lactic acid can be used.
  • caprolactone examples include ⁇ -caprolactone, ⁇ -caprolactone, ⁇ -caprolactone, and ⁇ -caprolactone is preferable.
  • the average chain length of the repeating unit of lactide in the copolymer is, for example, preferably 10 or less, and more preferably 6 or less.
  • the "average chain length, which is a repeating unit of lactide in a copolymer,” means the average number of molecules to which lactide (two lactic acid molecules) opened during copolymerization are continuously bonded. ..
  • the average chain length of the lactide is 10 or less, for example, the obtained film is more flexible.
  • Such a copolymer can be obtained, for example, by setting the polymerization temperature high, and specifically, by setting the polymerization temperature relatively high, the average chain length is set relatively small. be able to.
  • the polymerization temperature is preferably 100 to 170 ° C., for example.
  • the resin layers 3 and 6 have an appropriate thickness from the viewpoint of achieving both an appropriate barrier property and flexibility suitable for living tissue.
  • the thickness of the resin layers 3 and 6 is preferably 5 ⁇ m or more and 150 ⁇ m or less, more preferably 5 ⁇ m or more and 110 ⁇ m or less, and has high flexibility, from the viewpoint of achieving both appropriate barrier properties and flexibility suitable for living tissues. From the viewpoint of ensuring the above, it is more preferably 10 ⁇ m or more and 70 ⁇ m or less.
  • the flexural rigidity of the laminate consisting of the base material layer and the resin layer fixed to one of the main surfaces of the base material layer is the base material layer from the viewpoint of achieving both appropriate barrier properties and flexibility suitable for living tissue. It is preferably less than 7 times, more preferably less than 5 times, and further preferably less than 2.5 times the flexural rigidity of the single material.
  • the weight of the resin layers 3 and 6 per unit area is preferably less than 180 g / m 2 , more preferably less than 130 g / m 2 , and more preferably, from the viewpoint of achieving both appropriate barrier properties and flexibility suitable for living tissue. Is less than 80 g / m 2.
  • the non-permeable resin film used for forming the resin layers 3 and 6 is manufactured by a general method such as extrusion molding. Any of the non-stretched film, the uniaxially stretched film, and the biaxially stretched film can be suitably used as the material of the resin layers 3 and 6.
  • the use of the prosthetic material of the present invention is not particularly limited, and examples thereof include artificial blood vessels, vascular patches, hernia treatment sheets, dental tissue repair membranes, etc., and are suitable for appropriate barrier properties and living tissues. Since it is possible to achieve both flexibility, it can be suitably used as a prosthetic material for soft tissues of a living body. Examples of soft tissues include blood vessels, peritoneum, pleura, fascia, skin, gingiva and the like.
  • the preferred production method comprises non-absorbable porous substrate layers 2 and 5 and non-permeable resin layers 3 and 6 fixed to the porous substrate layers 2 and 5 and containing an absorbent material.
  • a method for producing a medical prosthetic material which comprises a step of thermocompression bonding a non-absorbable porous base material and a non-permeable film containing an absorbent material.
  • the absorbent material is a copolymer having a molar ratio of lactide to caprolactone (lactide: caprolactone) of 65:35 to 80:20.
  • the film thermocompression bonded to the base material is fixed to the base material and is fixed to the non-absorbable porous base material layers 2 and 5 and the non-water permeable material containing the absorbent material.
  • a prosthetic material containing the resin layers 3 and 6 is produced.
  • the base material In the method of forming a resin layer on the base material by adhering the base material with a good solvent of the absorbent material or dipping the absorbent material, the base material has absorbency in pores or interfiber voids. Since the material invades and solidifies, the rigidity of the prosthetic material becomes high, which is not preferable.
  • the good solvent of the absorbent material is an organic solvent, which is harmful. From the viewpoint of the risk of toxicity due to the residual solvent, the production environment, and environmental pollution, a production method that does not use an organic solvent is preferable.
  • a copolymer having a specific composition is selected as the absorbent material, and the film is fixed to the porous substrate by thermocompression bonding.
  • the film can be fixed to the base material while ensuring the properties. Therefore, according to the preferred production method of the present invention, it is possible to provide a prosthesis material capable of achieving both appropriate barrier properties and flexibility suitable for living tissue.
  • the method of fixing the film to the substrate is a thermocompression bonding method that utilizes the thermoplasticity of the absorbent material that constitutes the film because it avoids the use of harmful organic solvents.
  • the film may be heated at a temperature higher than the melting temperature of the copolymer and the softened film may be pressure-bonded to the base material. You may pressurize while heating both of them using a machine). If the temperature of the heat press is too high, thermal decomposition of the absorbent material will occur, so temperature control is required.
  • the preferred heating temperature is 110 ° C. or higher and 200 ° C. or lower, preferably 130 ° C. or higher and 170 ° C. or lower.
  • the pressure at the time of crimping is not particularly limited as long as the film can be reliably fixed to the base material and the porous structure of the base material is not deformed.
  • the method for producing the film is not particularly limited, and the film can be produced by a conventionally known film forming method such as an extrusion molding method, a pressing method, or a casting method.
  • a pressing method when the pressing method is adopted, pellets of the copolymer can be prepared and pressed with a hot press to form a film.
  • the conditions of the hot press are not particularly limited, but generally, the temperature is 120 to 200 ° C. and the pressure is 1 to 10 MPa.
  • the casting method for example, the copolymer is dissolved in a solvent to prepare a polymer solution, which is then cast on a flat surface to volatilize the solvent and form a film.
  • the solvent is not particularly limited, and examples thereof include 1,4-dioxane, dimethyl carbonate, chloroform, dichloromethane and the like.
  • the base material used in the above-mentioned preferable production method of the present invention becomes a base material layer when the film is fixed, and the shape, material, form, thread shape, hole diameter, and interfiber gap length of the base material are formed. Is the same as that of the above-mentioned base material layer.
  • the film used in the above preferable production method of the present invention becomes resin layers 3 and 6 by being fixed to the base material, but the material, thickness, weight per unit area and the like of the film are described in the resin layers 3 and 3. It is the same as that of 6.
  • the weight average molecular weight of the polymer is the GPC (gel permeation chromatography) method in which the polymer is dissolved in chloroform, column K-806L (Showa Denko Co., Ltd.), eluent: chloroform is used, and standard polystyrene is used as the standard substance.
  • the weight average molecular weight was measured by
  • the film was cut to a size of 1 cm ⁇ 1 cm and its weight was measured.
  • Example 1 Polyester plain weave sheet having a thickness of 450 [mu] m (hereinafter, untreated plain weave sheet) to, L- copolymer of lactide and the molar ratio of ⁇ - caprolactone 70:30 (weight average molecular weight: 2.0 ⁇ 10 5) of the sheet A non-porous resin film (weight per unit area: 71.4 g / m 2 , thickness 60 ⁇ m) obtained by processing into a shape was thermocompression bonded at 150 ° C. to obtain a prosthesis material A.
  • ⁇ Flexural rigidity> The prosthesis material A and the untreated plain weave sheet were each processed into a size of 3 cm ⁇ 5 cm, and the flexural rigidity was evaluated using a pure bending tester (manufactured by Kato Tech Co., Ltd.). As a result, the flexural rigidity of the prosthesis A and the untreated plain weave sheet was 0.1465 gf ⁇ cm / cm and 0.0699 gf ⁇ cm / cm, respectively, and the magnification of the flexural rigidity of the prosthesis A with respect to that of the untreated plain weave sheet. was 2.10 times (see Table 2 below).
  • Example 2 The same untreated plain weave sheet as in Example 1, L-copolymer of lactide and the molar ratio of ⁇ - caprolactone 70:30 (weight average molecular weight: 2.0 ⁇ 10 5) and the obtained by processing into a sheet A non-porous resin film (weight per unit area: 178.5 g / m 2 , thickness 150 ⁇ m) was thermocompression bonded at 150 ° C. to obtain a prosthesis material B.
  • the prosthesis material B was processed to a size of 3 cm ⁇ 5 cm in the same manner as in Example 1, and the flexural rigidity was evaluated using a pure bending tester (manufactured by Kato Tech Co., Ltd.). As a result, the flexural rigidity of the prosthesis B was 0.4336 gf ⁇ cm / cm, and the ratio of the flexural rigidity of the prosthesis B to that of the untreated plain weave sheet was 6.20 times (see Table 2 below). ..
  • Example 1 The same untreated plain weave sheet as in Example 1, poly L- lactic acid (weight average molecular weight: 4.5 ⁇ 10 5) a non-porous resin film obtained by processing into a sheet (weight per unit area: 71 .4 g / m 2 , thickness 60 ⁇ m) was thermocompression bonded at 210 ° C. to obtain a prosthetic material C.
  • the prosthesis material C was processed to a size of 0.5 cm ⁇ 5 cm, and the flexural rigidity was evaluated using a pure bending tester (manufactured by Kato Tech Co., Ltd.). As a result, the flexural rigidity of the prosthesis C was 0.8281 gf ⁇ cm / cm, and the ratio of the flexural rigidity of the prosthesis C to that of the untreated plain weave sheet was 11.85 times (see Table 2 below). ..
  • Example 3 A copolymer with a molar ratio of L-lactide and ⁇ -caprolactone of 70:30 (weight average molecular weight:) on a polypropylene mesh (trade name: Proleen mesh, manufactured by Ethicon) (hereinafter, untreated mesh) with a thickness of 300 ⁇ m.
  • a non-porous resin film (weight per unit area: 71.4 g / m 2 , thickness 60 ⁇ m) obtained by processing 2.0 ⁇ 10 5 ) into a sheet is thermocompression bonded at 150 ° C. and prosthesis. Material D was obtained.
  • ⁇ Flexural rigidity> The prosthesis material D and the untreated mesh were each processed into a size of 3 cm ⁇ 5 cm, and the flexural rigidity was evaluated using a pure bending tester (manufactured by Kato Tech Co., Ltd.). As a result, the flexural rigidity of the prosthesis D and the untreated mesh was 0.4637 gf ⁇ cm / cm and 0.4347 gf ⁇ cm / cm, respectively, and the magnification of the flexural rigidity of the prosthesis D with respect to that of the untreated mesh was 1. It was .07 times (see Table 2 below).
  • a non-porous resin film (weight per unit area: 71.4 g / m 2 , thickness 60 ⁇ m) obtained by processing the film into a sheet was thermocompression bonded at 150 ° C. to obtain a prosthesis material E.
  • ⁇ Flexural rigidity> The prosthesis material E and the untreated porous sheet were each processed into a size of 3 cm ⁇ 5 cm, and the flexural rigidity was evaluated using a pure bending tester (manufactured by Kato Tech Co., Ltd.). As a result, the bending rigidity of the prosthesis E and the untreated porous sheet was 0.1476 gf ⁇ cm / cm and 0.1571 gf ⁇ cm / cm, respectively, which of the untreated porous sheet having the bending rigidity of the prosthesis E. The ratio was 0.94 times (see Table 2 below).
  • Example 5 Copolymer in a molar ratio of L- lactide and ⁇ - caprolactone 69:31 (weight average molecular weight: 2.0 ⁇ 10 5) of 0.99 ° C., hot pressed under the conditions of 10 MPa, 20 min (10T, Toyo Seiki Seisakusho) A non-porous resin film having a weight per unit area of 60 g / m 2 and a thickness of 50 ⁇ m was prepared.
  • the produced film was punched into a JIS K7161-2 type1BA shape for use in a tensile tester.
  • a decomposition test simulating the in-vivo environment was performed on the obtained test sample in accordance with ISO15814. Specifically, the sample was immersed in a phosphate buffer solution adjusted to pH 7.4, sealed, and incubated at a temperature of 37 ⁇ 1 ° C. for 12 weeks. After a lapse of a predetermined period, the sample was taken out, the presence or absence of change in appearance, and the tensile strength of the sample were evaluated using a tensile tester, and the results are shown in Table 3.
  • Examples 6 to 8, Comparative Examples 2 to 3 As shown in Table 4 below, the pellets of the copolymers with different composition ratios were heat-pressed (10T, Toyo Seiki Seisakusho) at 140 ° C. and 10MPa, and the weight per unit area was 178g / m 2 and the thickness. A non-porous resin film having a size of 150 ⁇ m was prepared.
  • the obtained film (length 10 mm, width 20 mm) was sterilized with ethylene oxide gas (EOG), wrapped around the dog's flexor tendon (elliptical column with a diameter of about 2-4 mm), and the films were sutured together. It was fixed to the tendon.
  • EOG ethylene oxide gas
  • those that could be wound without causing cracks, cracks, etc. were judged to be flexible, and the samples that could not be wound because the film was hard were judged to be inflexible, and the results are shown in the table below. Shown in 4.
  • the present invention it is possible to prevent blood leakage and infiltration of living tissue in a living body for a certain period of time while suppressing impairing the flexibility of the base material constituting the conventionally used prosthetic material. Since it is possible to secure the barrier property of being able to do so, it is possible to provide a highly safe medical prosthetic material.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Composite Materials (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Materials For Medical Uses (AREA)

Abstract

Selon la présente invention, un matériau prothétique médical 1 comprend : une couche de substrat poreux non absorbant 2 ; et une couche de résine 3 imperméable à l'eau fixée à la couche de substrat poreux non absorbant 2 et contenant un matériau absorbant, le matériau absorbant étant un copolymère dont le rapport molaire entre le lactide et l'oxépan-2-one (lactide:oxépan-2-one) est de 65:35 à 80:20. Le poids par unité de surface de la couche de résine 3 est de préférence inférieur à 180 g/m2, de préférence encore, inférieure à 130 g/m2, et de préférence encore, inférieure à 80 g/m2. Ainsi, l'invention concerne un matériau prothétique médical apte à obtenir à la fois une propriété de barrière, avec laquelle une fuite de fluide corporel ou une infiltration dans des tissus biologiques peut être correctement préservée, et une flexibilité adaptée aux tissus biologiques.
PCT/JP2020/033524 2019-09-05 2020-09-04 Matériau prothétique médical Ceased WO2021045177A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0677600B2 (ja) * 1989-02-07 1994-10-05 テルモ株式会社 生体器官用補綴材
JP2004313310A (ja) * 2003-04-14 2004-11-11 Ube Ind Ltd 管状の人工器官
JP2005517062A (ja) * 2002-02-06 2005-06-09 ポリガニックス ビー． ブイ． ＤＬ−ラクチド−ε−カプロラクトンコポリマー
WO2014192803A1 (fr) * 2013-05-31 2014-12-04 学校法人同志社 Matrice de régénération de tissu

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0677600B2 (ja) * 1989-02-07 1994-10-05 テルモ株式会社 生体器官用補綴材
JP2005517062A (ja) * 2002-02-06 2005-06-09 ポリガニックス ビー． ブイ． ＤＬ−ラクチド−ε−カプロラクトンコポリマー
JP2004313310A (ja) * 2003-04-14 2004-11-11 Ube Ind Ltd 管状の人工器官
WO2014192803A1 (fr) * 2013-05-31 2014-12-04 学校法人同志社 Matrice de régénération de tissu

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PARK JI, LEE BO, PARK SEUNG, KIM MAL, LEE JIN, LEE HYE, LEE HAI, KIM JAE, KIM MOON: "Preparation of Biodegradable and Elastic Poly ( caprolactone-co-lactide) Copolymers and Evaluation as a Localized and Sustained Drug Delivery Carrier", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 18, no. 3, 21 March 2017 (2017-03-21), pages 671 - 15, XP055798757 *

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