WO2004075939A1 - Resine biodegradable, materiau medical pour la regeneration contenant du phosphate de calcium et son procede de production - Google Patents

Resine biodegradable, materiau medical pour la regeneration contenant du phosphate de calcium et son procede de production Download PDF

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Publication number
WO2004075939A1
WO2004075939A1 PCT/JP2004/002121 JP2004002121W WO2004075939A1 WO 2004075939 A1 WO2004075939 A1 WO 2004075939A1 JP 2004002121 W JP2004002121 W JP 2004002121W WO 2004075939 A1 WO2004075939 A1 WO 2004075939A1
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calcium phosphate
medical material
biodegradable resin
regenerative
weight
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PCT/JP2004/002121
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English (en)
Japanese (ja)
Inventor
Yuzuru Sugano
Kenzo Susa
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Trial Corporation
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Priority to JP2005502881A priority Critical patent/JP3831402B2/ja
Publication of WO2004075939A1 publication Critical patent/WO2004075939A1/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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic 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
    • 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 regenerative medicine material containing a biodegradable resin and calcium phosphate and a method for producing the same.
  • the present invention relates to an absorbable regenerative medical material (also referred to as a “tissue repair material”) that is suitably used for regenerating defective bone tissue, tooth tissue, and other living tissues.
  • tissue repair material also referred to as a “tissue repair material”
  • Regenerative medicine that regenerates jawbone and tooth tissue has attracted attention.
  • a biodegradable material that is biocompatible and is gradually degraded and absorbed in vivo is used as a matrix (substrate).
  • biodegradable plastics such as polylactic acid, polydalicholic acid, and polylactide prolactone (edited by Biodegradable Plastics Study Group, editor-in-chief Yoshiharu Dohi, Plastic Handbook ", EN * T.S. Co., Ltd., the first edition of the first edition issued on May 26, 1995).
  • polylactic acid and a copolymer of the same with another biodegradable and absorbable polymer may be woven or formed into a porous form, or the hydroxyapa may be used.
  • a mandibular reconstruction material and a mesh tray for mandibular reconstruction covered with tight have also been proposed (see JP-A-5-42202 and JP-A-5-309103).
  • the material (reconstruction material) disclosed in the above-mentioned patent has biodegradability, and it is difficult to control the degradation rate in the living body.
  • the decomposition rate of these biodegradable resins in the living body is accelerated with the passage of time, and the acidity inside the matrix increases, and the area where the matrix is embedded tends to become inflamed.
  • the matrix usually contains calcium phosphate, a substance necessary for tissue repair, but has a problem in that its content is low. Disclosure of the invention
  • the problem to be solved by the present invention is to provide a regenerative medicine material (tissue repair material) which can contain such calcium phosphate in an arbitrary ratio and is excellent in safety, functionality and biocompatibility. Another object is to provide a simple method for producing such a regenerative medical material.
  • the present inventors have conducted various studies. As a result, one of the present inventors has developed a method for producing a spherical composite powder (Japanese Patent Laid-Open Publication No. 2002-114901). The present invention has been completed by developing the technology. That is, the present invention provides
  • Biodegradable resin 99.9- regenerative medicine material characterized by containing 10% by weight and 0.1-90% by weight of calcium phosphate kneaded in the biodegradable resin; It is.
  • the present invention also provides a simple method for producing such a regenerative medical material. That is, the manufacturing method is based on the following steps (i) to '(iiii),
  • calcium phosphate which is the key of a tissue repair substance can be contained in a base material in arbitrary ratios, and it is excellent in safety, functionality, and biocompatibility, As such, it can provide regenerative medicine materials (tissue repair materials) that are absorbed and lost.
  • BEST MODE FOR CARRYING OUT THE INVENTION As described above, the material for regenerative medicine of the present invention comprises 99.9 to 10% by weight of a biodegradable resin and 0.1 to 90% by weight of calcium phosphate kneaded in the biodegradable resin. a reproduction medical material containing a weight 0/0.
  • the biodegradable resin (substrate) used in the present invention is a biodegradable thermoplastic resin (biodegradable thermoplastic resin) for easily producing the regenerative medical material of the present invention and enhancing safety. (Fat).
  • biodegradable thermoplastic resins are fatty acid polyesters (including polylactic acid), specific biodegradable thermoplastic resins obtained by chemically modifying natural raw materials, microorganism-produced plastics and synthetic plastics. However, it is not limited to these.
  • Aliphatic polyester is a polyester in which all carbon atoms in the molecule are connected in a single chain, and the carbon atoms in the molecule may have a branched structure, but do not contain a cyclic structure. .
  • Aliphatic polyesters are produced on an industrial scale, and preferred aliphatic polyesters for the practice of the present invention include polylactic acid by a ring-opening polymerization method.
  • PHA polyhydroxybutylate / valerate copolymer
  • PHB polyhydroxybutylate / valerate copolymer
  • a specific biodegradable thermoplastic resin obtained by chemically modifying a natural material is cellulose acetate.
  • Cellulose acetate having an acetate substitution degree of 2.5 or less can be used as a biodegradable thermoplastic resin.
  • a plasticizer may be used in combination.
  • Microbial polyesters, microbial polybran and microbial polyamino acids are typical examples of microbial plastics, and microbial polyesters are preferred in the present invention.
  • microbial polyesters examples include poly [(R) -3-hydroxybutyrate (abbreviated P (3HB))].
  • Microbial copolymerized polyesters such as copolymers of 3-hydroxybutylate and 3-hydroxyparylate (abbreviated as P (3HB-cG-3HV)), etc., depend on the monomer composition. It can be used more preferably because its physical properties can be varied widely.
  • P (3HB-co-3HV) As the biodegradable thermoplastic resin used in the present invention, a specific modified synthetic plastic can also be used. These modified synthetic plastics include poly (3-hydroxyalkanoate), (abbreviated as P (3HA)), biodegradable methacrylate resin, and other biodegradable copolymers. Are mentioned.
  • Biodegradation An example of a 1 "raw methacrylate ester resin is polymethyl methacrylate into which a pyridinium group has been introduced.
  • Biodegradable copolymers include copolyesters, copolyesterethers, copolyestercarbonates, and copolyesteramides.
  • thermoplastic resin For the biodegradable thermoplastic resin, see Biodegradable Plastics Research Group, edited by Yoshiharu Dohi, "Biosynthetic Needle Raw Plastic Handbook", N.T.S. The first edition of the first edition is issued on the 6th, and is described in detail in.
  • Table 1 lists the types of available biodegradable thermoplastic resins and their manufacturing capabilities.
  • biodegradable resins it is preferable to use an aliphatic polyester or a blend of two or more fatty acid polyesters. Among them, polylactic acid is most preferably used.
  • biodegradable luster and other luster may be blended and used, or may contain various fillers.
  • phosphoric acid is used together with the biodegradable resin.
  • the calcium phosphate hydroxyapatite, calcium a-phosphate, j3-calcium phosphate, T / calcium monophosphate, octacalcium phosphate and the like can be used. Two or more calcium phosphates may be used in combination.
  • Calcium phosphate not only acts as a source of major inorganic salts in bone and tooth tissues, but also helps cells adhere to substrates and promotes cell growth. In addition, it also has an action of relaxing the acid generated by the decomposition of the biodegradable resin.
  • the method for producing calcium phosphate used in the present invention is not particularly limited, but it may be produced by a dry method, a hydrothermal method, or a wet method, and may be subjected to a heat treatment.
  • the average particle size of the calcium phosphate used in the present invention is not particularly limited, but is preferably from 0.1 ⁇ to 500 ⁇ , and more preferably from 0.1 ⁇ to 500 / m. .
  • the content of calcium phosphate in the regenerative medical material of the present invention is 0.1 to 90% by weight, preferably 1 to 5% by weight, and more preferably 2 to 3% by weight.
  • One preferred shape (structure) of the regenerative medical material of the present invention is a microsphere.
  • Another preferred shape (structure) of the regenerative medical material of the present invention is a fibrous or nonwoven fabric, a sponge, or a specific shape obtained by combining microspheres.
  • the average particle size is preferably 1 ⁇ m or more and 300 ⁇ m or less.
  • the thickness (diameter) of the fiber when the shape is fibrous or non-woven or the thickness (diameter) of the skeleton when the shape is sponge-like or a specific shape (in which microspheres are combined),
  • the average value is preferably 1 im or more and 500 m or less.
  • any of the regenerative medical materials of the present invention is made of a composition comprising a biodegradable resin (preferably, biodegradable and thermoplastic), calcium phosphate, and additives to be added as necessary. Heated above the softening point of biodegradable fat with no water-soluble dispersion medium It can be obtained by mixing, dispersing, cooling to a temperature below the softening point and then removing the water-soluble dispersion medium using an aqueous developing solvent.
  • a biodegradable resin preferably, biodegradable and thermoplastic
  • calcium phosphate preferably, calcium phosphate, and additives to be added as necessary. Heated above the softening point of biodegradable fat with no water-soluble dispersion medium It can be obtained by mixing, dispersing, cooling to a temperature below the softening point and then removing the water-soluble dispersion medium using an aqueous developing solvent.
  • the obtained regenerative medicine material has a fibrous or nonwoven fabric force, a sponge force, or a microsphere shape is usually determined by a biodegradable resin (o) and a water-soluble dispersion medium ( w) and the volume ratio. If the amount of the water-soluble dispersion medium is larger than that of the biodegradable resin, for example, if the volume ratio of the water-soluble dispersion medium to the luster is 6: 4 or more, the biodegradable resin becomes completely island-shaped, and Due to the two-phase separation structure (sea-island structure), the shape of the resulting regenerative medicine material is microspherical.
  • the volume ratio between the biodegradable resin and the water-soluble dispersing medium is almost half, for example, if the volume ratio between the water-soluble dispersing medium and the resin is approximately 5: 5, the islands (microspheres) will be connected to each other by land, resulting in The shape of the regenerative medicine material is a sponge-like (or similar). Further, when the amount of the biodegradable resin is slightly larger than the amount of the water-soluble dispersion medium, for example, when the volume ratio of the resin to the water-soluble dispersion medium is close to 5.5: 4.5, the obtained regenerative medical material cannot The shape is fibrous or non-woven.
  • thermoplastic resin and at least one filler are used.
  • the resulting composition is mixed with a water-soluble dispersing medium and a water-soluble dispersion medium by heating and mixing above the softening point of the composition, dispersing it as fine particles, and then cooling to give 0.01 ⁇ m.
  • a spherical composite powder having a length of not less than m and not more than 1,000 ⁇ is obtained.
  • the desired spherical particles can be separated from the water-soluble dispersion medium by washing with an aqueous developing solvent.
  • Preferred examples of the water-soluble dispersion medium used in the present invention include polyalkylene oxides (such as polyethylene glycol), homopolymers or copolymers of polyalkene carboxylic acids, and salts thereof (eg, polyacrylic acid, polymethacrylic acid). Acid, sodium polyacrylate), polyalkeneamide homopolymer or copolymer (polyacrylamide, polymethacrylamide) and the like, and these can be used alone or in combination.
  • polyalkylene oxides such as polyethylene glycol
  • homopolymers or copolymers of polyalkene carboxylic acids and salts thereof (eg, polyacrylic acid, polymethacrylic acid). Acid, sodium polyacrylate), polyalkeneamide homopolymer or copolymer (polyacrylamide, polymethacrylamide) and the like, and these can be used alone or in combination.
  • polylactic acid When polylactic acid is used as the biodegradable resin, it is particularly preferable to use polyarythalic acid as the water-soluble dispersion medium.
  • the method and apparatus for dispersing the biodegradable resin and calcium phosphate in the soluble dispersion medium are not particularly limited.
  • it can be dispersed by a roll, a Banbury mixer, a kneader, a short screw extruder, a twin screw extruder, or the like.
  • the mixture When heating and mixing the biodegradable resin and calcium phosphate in the water-soluble dispersion medium, it is preferable to heat the mixture to a temperature higher by 10 ° C to 2 ° C higher than the softening point of the biodegradable resin used. Is preferably heated to a temperature higher by 20 ° C. to 150 ° C. and mixed. After mixing the biodegradable thermal resin, calcium phosphate and the water-soluble dispersion medium, the mixture is cooled to a temperature lower than the softening point of the biodegradable resin.
  • the mixture is usually mixed with a developing solvent that is a poor solvent for the biodegradable resin and calcium phosphate and is a good solvent for the water-soluble dispersion medium, and the water-soluble dispersion medium is removed.
  • a developing solvent that is a poor solvent for the biodegradable resin and calcium phosphate and is a good solvent for the water-soluble dispersion medium
  • the cooled molded product may be crushed with a crusher or the like and then immersed in a developing solvent.
  • the microspheres after cooling may be pelletized with a pelletizer.
  • the hot mixture before cooling may be formed into a sheet or a desired structure by an extruder, a roll, or the like, and then immersed in a developing solvent.
  • the developing solvent water or an aqueous organic solvent can be used.
  • water-soluble dispersion medium is a polyalkylene oxide or a polyalkylene carboxylic acid
  • water can be used as a developing solvent.
  • the water-soluble dispersing medium is removed together with the developing solvent by centrifugation, filtration, or a combination of these methods. Then, if necessary, dry before use.
  • a step of cooling to a temperature and a step of removing the water-soluble dispersion medium using an aqueous developing solvent, to obtain a regenerative medical material of a specific shape obtained by combining fibrous or nonwoven fabric, sponge, or microspheres.
  • a mixture containing a biodegradable resin and calcium phosphate is heated and mixed at a temperature equal to or higher than the softening point of the biodegradable resin, and then spun.
  • Materials can also be manufactured.
  • various foaming agents gas such as nitrogen and chlorofluorocarbon, and chemical foaming agents such as sodium hydrocarbon
  • foaming agents gas such as nitrogen and chlorofluorocarbon, and chemical foaming agents such as sodium hydrocarbon
  • Chemical, physical, and mechanical means can be used to combine the spherical particles into a specific shape. For example, coalescence by chemical bonding, adhesion using an adhesive, and coalescence by magnetism are mentioned.
  • the regenerative medical material of the present invention is further coated with a layer made of calcium phosphate by dispersing or immersing it in an aqueous solution containing Ca ions and phosphate ions at a temperature of 30 ° C. or more for 12 hours or more. can do.
  • aqueous solution it is necessary to contain at least C a and phosphate ions (HP0 4 2).
  • a simulated body fluid containing Ca ions or phosphate ions is used.
  • the aqueous solution needs to be in a supersaturated state of calcium phosphate.
  • it is important to maintain the pH of the aqueous solution above neutral. When the pH decreases, crystals do not precipitate because the solubility of calcium phosphate increases.
  • the Ca ion concentration is preferably 1.0 (mM / L) or more, and more preferably 2.0 to 7.5 (mM / L).
  • the phosphate ion concentration is preferably 0.4 (mM / L) or more, and more preferably 0.8 to 3.0 (mM / L).
  • MMZ L simulated body fluid
  • various ion concentrations in simulated body fluid is, Ca 2 +: 2. 5, HP0 4 2 _: 1. 0, Na +: 142, K +: 5. 0, mg 2 +: 1. 5, C I-: 147. 8, HC0 3 -: 4. 2, S0 4 2 -: 0. 5 and buffer (CH 2 OH) 3 CNH 2 concentrations 50 (mM / L )) Or an aqueous solution having a concentration of 1 to 3 times these concentrations.
  • the pH value of the aqueous solution during immersion is 7.2 to 8.0, preferably 7.4 to 7.6, the temperature is 30 to 80 ° C, preferably 36 to 38 ° C, and the immersion time is 12 hours or more, preferably Is 3 to 10 days.
  • the regenerative medical material before coating is suspended in the aqueous solution.
  • Floating makes it possible to provide a coating without unevenness.
  • a regenerative medical material whose surface is covered with a layer made of calcium phosphate can be produced.
  • the calcium phosphate as a coating layer octacalcium phosphate (C a 8 H 2 (P 0 4) 6 ⁇ 5 H 2 O) Ya hydroxy ⁇ Pas tight (C a 1 0 (P 0 4) 6 (OH) 2 ), But is preferably hydroxyapatite. Of hydroxyapatite, bone-like apatite is more preferable.
  • Bonraikua apatite refers hydroxycarboxylic ⁇ Pas tight P 0 4 3 - a part of the ion CO 3 2 Ichii ON substituted, partially N a of C a 2 + ions for maintaining electrical neutrality Apatite that has been replaced by + ions, resulting in a Ca / P ratio of less than 1.67.
  • the regenerative medicine material of the present invention can be used as a substrate that promotes cell differentiation and production of interstitial cells and is itself gradually degraded.
  • One of the preferable shapes (structures) of the regenerative medical material obtained by the present invention is sponge-like (porous) as described above.
  • the size of the pores (voids) when in the form of a sponge (porous) has an average diameter of 1 to 500 ⁇ , and particularly preferably 50 to 500 ⁇ . If the pore size exceeds 500 m, cells are likely to be lost or lost from the matrix when cells are taken up. If the pore size is smaller than 1 ⁇ m, the cells cannot be taken up into the deep area of Matritus. By heat-sealing the microspheres, a porous regenerative medical material having a specific shape can be obtained.
  • the regenerative medical material of the present invention can also be chemically crosslinked.
  • a crosslinking agent Cyanamide can be exemplified.
  • the regenerative medical material in the present invention may contain at least one kind of physiologically active substance.
  • physiologically active substance include compounds that optimize the matrix properties of the incorporated cells, such as antibiotics, compounds that improve cell adhesion, and inducers.
  • Antibiotics are used to reduce inflammation resulting from rejection at the time of transplantation.
  • Examples of compounds that improve cloxa cell adhesion include poly-L-lysine and fibronectin.
  • inducing factor examples include fibroblast growth factor (bFGF), insulin-like growth factor (IGF), transforming growth factor (TGF-0), and vascular endothelial cell growth factor (VEGF).
  • bFGF fibroblast growth factor
  • IGF insulin-like growth factor
  • TGF-0 transforming growth factor
  • VEGF vascular endothelial cell growth factor
  • Substrates containing these inducing factors generate and produce differentiated tissues in vitro and in vivo from chondrocytes, mesenchymal stem cells and their progenitors, connective fibroblasts, and Z or osteoblasts. Especially suitable for.
  • Cells incorporated into the substrate include fetal chondrocytes obtained from abortion, adult mesenchymal stem cells and their progenitors obtained from bone marrow or periosteum, and fetal mesenchymal stem cells and their progenitors obtained from umbilical cord Can be exemplified.
  • the regenerative medical material obtained according to the present invention can be differentiated in vivo with or without pre-culture in vitro to obtain connective and supporting organs of various tissue types, especially cartilage tissue and bone tissue. Suitable for.
  • the shape of the regenerative medical material of the present invention is a fibrous or non-woven fabric, a sponge, a microsphere, or a specific shape obtained by combining microspheres. These can be used and divided according to the uses of regenerative medicine.
  • the regenerative medicine material having a sponge-like shape of the present invention is a rigid structure, it can be used for regenerative medicine for a tissue in which the shape of an ear, a finger, or the like is to be kept clear.
  • the regenerative medical material having a fibrous or nonwoven fabric shape of the present invention is used, for example, in the following cases. Liver stem cells are incorporated into a fibrous or non-woven regenerative medicine material coated with ⁇ -calcium phosphate, and the liver stem cells are grown in an in vitro mouth before being used as an artificial liver. As one embodiment of the regenerative medical material of the present invention, fine spherical particles can be used.
  • microspherical particles in the present invention can be produced according to the method for producing microspherical particles previously developed by the present inventor (JP-A-2001-114901). Spherical particles having a size of 1 im or more and 300 ⁇ m or less are preferable.
  • the microspherical particles of the present invention are dispersed or immersed in an aqueous solution containing Ca ions and phosphate ions at a temperature of 30 ° C or more for 12 hours or more. By doing so, the particle surface can be covered with a layer made of calcium phosphate.
  • microspherical particles promote cell differentiation and production of interstitial cells, as well as fibrous, non-woven, or sponge materials for regenerative medicine, and should be used as a material that is itself gradually degraded. Can be.
  • the regenerative medical material comprising the microspherical particles obtained by the present invention can contain at least one kind of physiologically active substance.
  • Fibrous, non-woven or sponge-shaped regenerative medical materials and regenerative medical materials composed of fine spherical particles are not different in terms of their physiological functions, but are distinguished in terms of their applications.
  • a regenerative medical material composed of microspherical particles has a smaller particle diameter than a fibrous or non-woven or sponge-like regenerative medical material, so that an artificial tissue that requires precision, such as an artificial blood vessel or an artificial blood vessel, is required.
  • Suitable as a material for artificial muscles is required.
  • a regenerative medicine material obtained by heat-sealing micro spherical particles into a specific shape can be used.
  • spherical particles can be combined according to the shape of the defect, and the gap can be filled with a physiologically active substance.
  • Example 1 To 1 kg of polylactic acid pellets (PLA4031 DK) manufactured by Unitika Ltd., add 30 g of calcium phosphate, and add 1.3 kg of polyacrylic acid pellets (Dyulymer AC-103 AP) manufactured by Nippon Pure Chemical Co., Ltd. After that, the mixture was kneaded in a pressure kneader at 180 ° C. for 10 minutes, and then stabilized at 190 ° C. for 5 minutes. Thereafter, the mixture was extruded from a kneader and cooled to 120 ° C., and then polyacrylic acid was dissolved and removed in about 20 liters of dispersed water. As a result, fibrous or non-woven polylactic acid (about 10 mm thick) containing] 3-calcium phosphate was obtained.
  • the stem cells of the muscle separated from the thigh muscle of the rat are inoculated into the [3-calcium phosphate] of the above-mentioned fibrous or non-woven polylactic acid (thickness: about 10 mm) containing 13-calcium phosphate, cultured for 24 hours, and grown to some extent. At this time, muscle stem cells grow along the polylactic acid fiber. This is transplanted into the same rat at the site of muscle injury. One week later, part of the tissue at the transplant site is excised, and the tissue section is observed with an electron microscope. As a result, the transplant site is completely adhered to the original tissue, and the polylactic acid containing 8-phosphate is completely degraded.
  • microspheres were embedded in the damaged bone of the rat, and one month later, when the bone fracture was observed by X-ray examination, the polylactic acid dissolved and the fractured part disappeared. Growth is seen.
  • Example 2 The procedure is as in Example 1, except that the hot mixture extruded from the pressure kneader is applied thinly (approx. 0.5 mm) to a stainless steel vat and contains j8-calcium phosphate. A polylactic acid sheet-like nonwoven fabric having a thickness of about 0.5 mm was obtained.
  • the obtained sheet-shaped nonwoven fabric is cut into an appropriate size, and the cut nonwoven fabric is placed in a culture dish.
  • RPMAdd RPMI 1640 medium containing 10% fetal serum (volume) and separately treat the cells with trypsin, etc. to make a small amount of skin cells, and cultivate them at 37 ° C in a cell culture incubator. Skin cells are observed to grow on the sheet-like nonwoven.

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Abstract

La présente invention a trait à un matériau médical pour la régénération présentant une absorbabilité et étant d'utilisation appropriée dans des tissus dentaires, des tissus osseux et d'autres tissus biologiques défectueux. Le matériau médical pour la régénération est caractérisé en ce qu'il contient entre 10 et 99,9 % en poids d'une résine biodégradable et entre 0,1 et 90 % en poids de phosphate de calcium malaxé dans la résine biodégradable. Ainsi, le phosphate de calcium représentant un élément clé dans les matériaux de réparation peut être ajouté dans un rapport arbitraire à une base. En outre, le matériau médical de l'invention présente d'excellentes propriétés de sécurité, de fonctions et de biocompatibilité.
PCT/JP2004/002121 2003-02-26 2004-02-24 Resine biodegradable, materiau medical pour la regeneration contenant du phosphate de calcium et son procede de production WO2004075939A1 (fr)

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JP2005177096A (ja) * 2003-12-18 2005-07-07 Univ Nihon 柔軟性シート状骨補填材及びその製造方法
JP2006076980A (ja) * 2004-09-13 2006-03-23 National Institute For Materials Science 歯の再生材料とこれを利用した歯の再生方法
JP2006117835A (ja) * 2004-10-22 2006-05-11 Kao Corp ポリエステル樹脂用添加剤
JP2007222811A (ja) * 2006-02-24 2007-09-06 Higashi Nippon Gakuen Hokkaido Iryo Daigaku 高度先進医療に応用できる抜去歯粉砕品、抜去歯由来の脱灰粉体、脱灰粉体とアパタイトとの複合体を調製する方法および粉砕機
WO2009157543A1 (fr) * 2008-06-27 2009-12-30 公立大学法人大阪市立大学 Composition médicale et kit médical
JP2013159886A (ja) * 2012-02-08 2013-08-19 Eccera Co Ltd ポリ乳酸含有溶融紡糸及びその製造方法

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