WO2002049548A1 - Instrument a demeure - Google Patents

Instrument a demeure Download PDF

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Publication number
WO2002049548A1
WO2002049548A1 PCT/JP2001/000202 JP0100202W WO0249548A1 WO 2002049548 A1 WO2002049548 A1 WO 2002049548A1 JP 0100202 W JP0100202 W JP 0100202W WO 0249548 A1 WO0249548 A1 WO 0249548A1
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WO
WIPO (PCT)
Prior art keywords
porous metal
metal
indwelling device
pore
porous
Prior art date
Application number
PCT/JP2001/000202
Other languages
English (en)
Japanese (ja)
Inventor
Yuichi Mori
Hideo Nakajima
Yasuharu Noishiki
Yuichi Higuchi
Shigeki Honzu
Original Assignee
Yuichi Mori
Hideo Nakajima
Yasuharu Noishiki
Yuichi Higuchi
Shigeki Honzu
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Yuichi Mori, Hideo Nakajima, Yasuharu Noishiki, Yuichi Higuchi, Shigeki Honzu filed Critical Yuichi Mori
Priority to AU2001225537A priority Critical patent/AU2001225537A1/en
Publication of WO2002049548A1 publication Critical patent/WO2002049548A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
    • A61B17/68—Internal fixation devices, including fasteners and spinal fixators, even if a part thereof projects from the skin
    • A61B17/84—Fasteners therefor or fasteners being internal fixation devices
    • A61B17/86—Pins or screws or threaded wires; nuts therefor
    • A61B17/866—Material or manufacture
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0012—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/32—Joints for the hip
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/32—Joints for the hip
    • A61F2/34—Acetabular cups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/32—Joints for the hip
    • A61F2/36—Femoral heads ; Femoral endoprostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30108—Shapes
    • A61F2002/30199—Three-dimensional shapes
    • A61F2002/30224—Three-dimensional shapes cylindrical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30108—Shapes
    • A61F2002/30199—Three-dimensional shapes
    • A61F2002/30224—Three-dimensional shapes cylindrical
    • A61F2002/30235—Three-dimensional shapes cylindrical tubular, e.g. sleeves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30108—Shapes
    • A61F2002/30199—Three-dimensional shapes
    • A61F2002/30261—Three-dimensional shapes parallelepipedal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
    • A61F2002/30795—Blind bores, e.g. of circular cross-section
    • A61F2002/30807—Plurality of blind bores
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0063—Three-dimensional shapes
    • A61F2230/0069—Three-dimensional shapes cylindrical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0063—Three-dimensional shapes
    • A61F2230/0082—Three-dimensional shapes parallelepipedal

Definitions

  • the present invention relates to an indwelling device that can be indwelled (or placed) in a body by an operation such as transplantation, typically, for example, a medical device (for example, a surgical device (orthopedic surgery, brain surgery, etc.) or a dental device that can be used in a dental region)
  • Medical devices usable in the field of orthopedic surgery such as artificial bones that can be implanted into hard tissues such as bones, plates for fixing fractures, screws and wires, and clips and brains for ligating cerebral aneurysms
  • Medical tools such as a coil for filling an aneurysm that can be used in the field of brain surgery; medical tools that can be used in the dental field such as artificial dental roots, and stents).
  • the indwelling device according to the present invention has a stable state for a long period of time while achieving weight reduction and compatibility with internal tissues (preferably, further promoting healing, preventing infection, etc.) without reducing strength. Can be placed in the body.
  • One aspect of the indwelling device according to the present invention relates to a stent, and particularly, to patency the lumen (eg, blood vessel, bile duct, bronchus, urethra, digestive tract, etc.) narrowed or obstructed by a lesion.
  • the lumen eg, blood vessel, bile duct, bronchus, urethra, digestive tract, etc.
  • the stent of the present invention has various functions (for example, anti-thrombotic properties, hyperinhibition of intimal hyperplasia) while minimizing the weakening of the stent itself or peeling of the coating substance from the stent body as much as possible. ) Is extremely easy.
  • the stents of the present invention can be used, for example, for acute coronary occlusion or re- It can be particularly suitably used for an intervention therapy for stenosis.
  • the stent of the present invention can be suitably used in a treatment method for maintaining the patency of a lumen obstructed or narrowed by cancer or the like, utilizing the ease of imparting the function.
  • the application site and application method of the indwelling device of the present invention are not particularly limited, but for convenience of explanation, a conventional technique will be described using an example of “implanted device” which is a typical use method of the indwelling device in recent years.
  • metallic materials were the sole materials of their own.
  • cerebral aneurysm ligation clips and cerebral aneurysm filling coils used in the cerebral vascular region are also made of metallic materials because of their stability in the body, excellent mechanical strength, and good workability.
  • Stainless steel, titanium, platinum, tantalum, nickel / titanium alloys and shape memory alloys have been mainly used as metallic materials to be kept in the body.
  • the challenge that has been given to metal materials in the past 30 years is the affinity for tissue in the body, and the affinity with cells has been improving through the use of titanium and other materials and improvements in surface treatment such as ceramic processing by plasma irradiation.
  • the main cause may be that metal materials did not have an improvement means to fundamentally solve many of these problems. This leaves some adverse clinical phenomena neglected. For example, prosthesis in the elderly; plates, ports, and wires that fix hip joints, artificial heads, or fractures are too strong in metallic material and are too heavy to wear or destroy the patient's own bones Or inconvenience such as breaking.
  • the gingival fibers did not bind to the attachment, and bacteria could easily enter.
  • tissue of the body since it is impossible for tissue of the body to enter the metal material, when inserted into the body, the body tissue surrounds the entire metal material with the tissue of the body and “encapsulation, encapsulation” This phenomenon represents an extraterritorial jurisdiction within a single country, so if an infection occurs, even if a drug such as an antibiotic is used, Difficult to enter the territory, therapeutic effect is uncertain Be fruitful.
  • the metal material is extremely vulnerable to infection, because the infection spreads rapidly to the entire surface of the material at the boundary area between the inner surface of the encapsulated tissue and the material. Also results.
  • the application site and application method of the stent of the present invention are not particularly limited.
  • the typical application method of the stent in recent years is “interpension”.
  • Conventional technologies are described using “treatment” as an example.
  • stents have been clinically placed in the coronary artery for interventional treatment of acute coronary occlusion and restenosis after percutaneous coronary angioplasty (PTCA).
  • PTCA percutaneous coronary angioplasty
  • the recoil of the coronary artery was significantly reduced, and a good initial dilatation effect was observed.
  • the materials of stents that have been developed are metals, such as stainless steel, tantalum, titanium, and an alloy of titanium and nickel (Nitinol).
  • the structure can be broadly classified into a slotted tube stent having a tubular structure and a coil stent made of a single wire.
  • Methods for expanding these stents in a lumen such as a coronary artery that is stenotic or occluded include a method using a balloon catheter or the like, a method using a balloon, and a method in which the stent is folded into a catheter or a sheath. And a method of expanding the stent made of nitinol, which is a shape memory alloy, by a temperature change. ing.
  • metal which is the material of the stent, promotes thrombus formation. Stents also tend to cause the reocclusion or restenosis seen weeks to months after their placement, since metal is a foreign body to the body and promotes intimal proliferation.
  • Anticoagulants such as heparin and antiplatelet agents such as aspirin have been systemically administered to prevent thrombus formation due to stent placement, but these methods increase the risk of bleeding. There is a serious problem. '
  • a device for imparting antithrombotic properties to the stent itself has been devised.
  • structures have been devised to minimize the thickness of the stent or the metal surface area of the stent, but there are limitations to mechanically preventing recoil in the blood vessel. .
  • an anticoagulant such as heparin is contained in the polymer coating layer on the surface of the stent, and the anticoagulant is slowly released into the bloodstream. Attempts have been made to grant.
  • the coating thickness is increased, and the blood flow is locally disturbed at the stent placement portion, and conversely, a thrombus tends to be formed.
  • impregnating a large amount of drug reduces the mechanical strength of the coating polymer layer, and increases the tendency for problems such as peeling of the coating layer from the stent metal surface.
  • systemic administration of keloids and tranilast is a method of preventing intimal hyperproliferation that causes reocclusion or restenosis at the later stage of stenting, or A method using a catheter to locally irradiate the gamma ray or 3 rays to the stent placement part to suppress cell division and proliferation has been performed, and a certain effect has been observed.
  • An activation stent has also been developed in which P-32 is ion-implanted into the stent itself.
  • drugs such as tranilast, which suppresses the release of tumor growth factor (TGF-), interleukin-1 (IL-1), platelet-derived growth factor (PDGF), etc., during vascular disorders, are used in combination with the aforementioned anticoagulants.
  • TGF- tumor growth factor
  • IL-1 interleukin-1
  • PDGF platelet-derived growth factor
  • the drug is contained in a polymer film coated on the surface of the stent to make it release gradually.
  • An object of the present invention is to provide a device for indwelling in a body that has solved the above-mentioned disadvantages of the conventional technology.
  • Another object of the present invention is to provide an indwelling device having the same mechanical properties and excellent strength and lightness as the tissue surrounding the body.
  • Still another object of the present invention is to provide the stent with various functions (for example, antithrombotic properties, excessive vascular intima, etc.) while minimizing the weakening of the stent itself or the detachment of the coating substance from the stent body.
  • various functions for example, antithrombotic properties, excessive vascular intima, etc.
  • the metal indwelling device of the present invention is based on the above findings, and is an indwelling device including at least a part of a metal part, wherein at least a part of the metal part includes a porous metal. It is a characteristic.
  • the indwelling device of the present invention having the above-described structure is not only lightweight because the porous metal material constituting the device is porous, but also has a remarkably increased contact area with the body tissue, so that sufficient bonding strength can be easily obtained. You can get it.
  • the indwelling device has excellent mechanical strength, but also it is easy to show the same toughness as the hard tissue in the body .
  • the constituent metal material is porous (especially in the case of a structure of anisotropic pores that are swollen backward), the in-vivo tissue easily enters the inside. Further, it is easy to strengthen the bond between the metallic material and the surrounding body tissue. In this case, it is possible to control the degree of invasion of body tissue particularly by the size of the pore.
  • the pore size is 8 to 15 ⁇
  • the body tissue such as collagen fiber is 40 or more.
  • L is 0 m
  • the bone-like tissue is, and when it is 150 to 200 ⁇ m. It is said that each bone tissue penetrates into the pore. Therefore, precise control of the pore size is critical to strengthening the connection between the device and the surrounding body tissue.
  • connection between the indwelling device and the surrounding body tissue can be strengthened, for example, even if bone resorption, osteoporosis, or deterioration of bone re-performance occur.
  • the medical device is stably held in the body.
  • it is easy to obtain a joint strength enough to withstand occlusal force.
  • a fracture plate, bolt, wire, etc. it is easy to obtain sufficient joint strength.
  • the infected part is limited to the local area and does not cause a major obstacle.
  • the metal material constituting the indwelling device of the present invention having the above structure is porous, various functional substances (for example, drugs such as coagulants, anticoagulants, antibacterial agents, etc., Or a bioactive substance such as an accelerator or a cell, etc., if necessary, in combination with a polymer compound). Therefore, the functional substance can be gradually released from the surface of the medical device into the surrounding tissue, and healing promotion, antibacterial, anticoagulant, and anticoagulant effects can be positively imparted to the medical device. Is possible.
  • drugs such as coagulants, anticoagulants, antibacterial agents, etc.
  • a bioactive substance such as an accelerator or a cell, etc.
  • a porous metal having an anisotropic pore structure described later since the pore is an open type, it is possible to fill a large amount of a functional substance inside the porous metal and to release the porous metal gradually. It will be easier.
  • a cell growth promoting substance is used as the above-mentioned functional substance, for example, by gradually releasing the substance from the indwelling device of the present invention in the form of a filling coil in a cerebral aneurysm, It is possible to significantly promote the delay of vascular endothelialization, which has been a critical problem in the past.
  • the plate of the present invention in the form of a plate for fixing a fractured part and an artificial tooth root is used.
  • the sustained release of cell growth-promoting factors and the like from the placement instrument can significantly enhance healing.
  • an antibacterial agent or the like is used as a functional substance, it is possible to positively prevent infection, which was a major problem with artificial joints and artificial dental roots.
  • the strength of the porous metal can be easily further improved.
  • the porous metal in which the porous metal is produced using a metal-gas system and utilizing the difference in solubility of gas atoms in a molten state and a solidified state of the metal, the porous metal is maintained at a different strength while maintaining the strength of the porous metal. It is extremely easy to obtain an isotropic pore.
  • the solid solution strengthening layer can be easily formed on the inner surface of the pore by the reaction between metal atoms and gas atoms in the porous metal production process.
  • a ceramic layer can be formed on the inner surface of the pores of the porous metal by a chemical vapor deposition method or a physical vapor deposition method.
  • a ceramic layer on the inner surface of the pore can also be formed by ion implantation.
  • the stent is configured while suppressing weakening of the stent itself or peeling of the coating substance from the stent body as much as possible.
  • the porous metal itself constituting the stent has a porous structure. In addition, peeling of the coating substance from the stent body can be suppressed as much as possible.
  • the pore of the porous metal in which the pore of the porous metal is open, it becomes easier to release the drug or physiologically active substance filled in the pore from the surface of the porous metal.
  • the strength of the porous metal is maintained by maintaining the strength of the stent. It becomes even easier to develop and maintain sufficient strength to prevent recoil of blood vessel walls and the like. .
  • the strength of the porous metal can be further improved.
  • the porous metal is manufactured using a metal-gas system using the difference in solubility of gas atoms between the molten state and the solidified state of the metal, and while maintaining the strength of the porous metal, It is extremely easy to obtain a sex pore.
  • the solid solution strengthening layer can be easily formed on the inner surface of the pore by the reaction between the metal atom and the gas atom in the porous metal manufacturing process.
  • chemical vapor deposition or physical It is also possible to form a ceramics layer on the inner surface of the pores of the porous metal by a conventional vapor deposition method. Such a ceramic layer on the inner surface of the pore is formed by an ion planter. It is also possible to form by a method of drawing.
  • FIG. 1 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial joint.
  • FIG. 2 is a schematic plan view and a schematic cross-sectional view showing an example in which the indwelling device according to the present invention is in the form of a fracture portion fixing plate.
  • FIG. 3 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of a screw for fixing a fractured part.
  • FIG. 4 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial tooth root.
  • FIG. 5 is a schematic perspective view showing an example of a method for producing a hollow cylindrical sample for measuring pore directionality (S max / S min) of a porous metal.
  • FIG. 6 is a schematic perspective view showing an example of a method for producing a plate-like sample for measuring the pore directionality of porous metal.
  • FIG. 7 is a schematic perspective view showing an example of a method for producing a laminated sample for measuring the pore directionality of a porous metal.
  • FIG. 8 is a schematic cross-sectional view showing an example of a measurement method for measuring the pore directionality of a porous metal.
  • Figure 9 shows the ⁇ / ⁇ of “Lenton-type” porous copper manufactured using the metal-gas method. It is a rough showing an example of the relationship between (relative tensile strength) and porosity.
  • FIG. 10 is a schematic cross-sectional view showing an example of a device for producing a linear porous metal.
  • FIG. 11 is a schematic perspective view and a schematic cross-sectional view showing an example of a linear porous metal and an example of a relationship between a pore direction and a cooling direction.
  • FIG. 12 is a schematic cross-sectional view showing another example of an apparatus for producing a linear porous metal.
  • Fig. 13 is a graph showing an example of the relationship between the nitrogen partial pressure and the argon partial pressure of the mixed gas in the porous metal production method by the metal-gas method.
  • Fig. 14 corresponds to one condition of the graph in Fig. 13.
  • FIG. 15 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained corresponding to the other conditions of the graph of FIG.
  • FIG. 16 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained according to still another condition of the graph of FIG.
  • FIG. 17 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained under still other conditions in the graph of FIG.
  • FIG. 18 is a schematic plan view showing one embodiment of the stent of the present invention.
  • FIG. 19 is a schematic plan view showing another embodiment of the stent of the present invention.
  • FIG. 20 is a schematic plan view showing another embodiment of the stent of the present invention.
  • FIG. 21 is a graph of FIG. 3 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained according to one condition.
  • FIG. 22 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained corresponding to the other conditions of the graph of FIG.
  • FIG. 23 is a micrograph (magnification: 2.6 times) of a cross section of a porous metal obtained according to still another condition of the graph of FIG.
  • Figure 24 is a plot of the graph of Figure 13 obtained for yet other conditions. 1 33333333
  • the “in-vivo indwelling device” refers to a body by an operation such as transplantation.
  • a medical device that is temporarily or (semi) permanently placed or placed inside.
  • “medical device” is intended to be used for the diagnosis, treatment or prevention of human or animal disease, or to affect the structure or function of a human or animal body. It is said that the instrument is supposed to be.
  • body refers to a human or animal body. As long as the indwelling body has a significance (for example, preservation of the body tissue and prevention of deterioration), it includes not only the body tissue but also the body of the cadaver. In the present invention, a “body” indwelling device is used as long as at least a part of the indwelling device can be indwelled in a body tissue by invasion, penetration, or the like.
  • the “medical device” in the present invention is not particularly limited as long as the use of the porous metal is effective.
  • Typical examples of the “medical device” in the present invention include an artificial joint (FIG. 1), a plate for fixing a fractured part (FIG. 2), a screw (FIG. 3), a wire, an artificial root (FIG. 4), a cerebral artery Includes filling coil inside the aneurysm.
  • the term “stent” refers to a structure that is temporarily or semi-permanently placed inside a lumen to maintain the inner diameter of the lumen.
  • the structure of the stent is not particularly limited as long as it performs such a function.
  • shapes applicable to the stent of the present invention include shapes as shown in the schematic development views of FIGS.
  • Figure 1 shows the expanded view of a so-called “multi-link” type stent when it is expanded.
  • This stent can be produced, for example, by forming a shape as shown in FIG. 18 with a wire or the like and then welding it appropriately as shown by the arrow in the figure.
  • Fig. 19 shows the so-called “Palmats-Shiatsu” type stage.
  • Figure 2 shows a development view of the client when it is expanded.
  • This stent can be produced, for example, by directly “burning” a hollow cylindrical metal material using a laser or the like so that the metal material has a shape when expanded as shown in FIG. Monkey
  • Fig. 20 shows a developed view of a so-called "wiktor ⁇ 5X” type stent when it is expanded.
  • This stent can be manufactured by forming a shape as shown in FIG. 20 with a wire or the like, and then appropriately welding the same as in FIG. 18.
  • the porous metal constituting the stent of the present invention is not particularly limited as long as it has porosity, but those having the following physical properties can be particularly preferably used.
  • the porous metal constituting the indwelling device according to the present invention is not particularly limited as long as it has porosity, but those having the following physical properties can be particularly preferably used.
  • the porous metal constituting the indwelling device of the present invention preferably has an average pore size (pore diameter) force of about 0.1 to 100 m, more preferably about 0.5 to 500 ⁇ m.
  • pore size is preferably used, for example, by using a measuring device (trade name: Automated Perm-Porometer) manufactured by Porous Materials, Inc. in the United States. It is possible.
  • the porous metal constituting the stent of the present invention preferably has an average pore size (pore diameter) of about 0.1 to 50 mm, more preferably about 1 to 20 mm.
  • pore size is, for example, US Porous M It is suitable for use with a measuring device manufactured by aterials, Inc. (trade name: Automated Perm-Porometer). (Porocity)
  • the porous metal forming the indwelling device of the present invention preferably has a porosity (porosity or porosity) of about 5 to 80%, more preferably about 10 to 40%.
  • porosity is preferably J J edible using, for example, a measuring device (trade name: Automated Perm-Porometer) manufactured by Porous Materials, Inc. in the United States.
  • the porous metal constituting the indwelling device of the present invention preferably has a pore directionality (Smax / Smin) of 2 or more. Further, the directionality (Smax / Smin) is preferably 10 or more, more preferably 20 or more (particularly 50 or more). The directionality of such pores can be suitably measured by the following method. ⁇ Method of measuring pore direction>
  • a hollow metal cylinder (before rolling, inner diameter of the porous metal: about 3 mm) having a hollow cylindrical shape is prepared along the axial direction of the porous metal as shown in the schematic perspective view of Fig. 5.
  • the porous metal tube obtained above is cut at one point along the pore axis direction, and a porous metal plate (thickness: about 1 mm, size: about 12 mm) as shown in the schematic perspective view of FIG. X about 20 mip).
  • the porous metal plate obtained above is cut to a thickness of about 1 mm along a direction perpendicular to the pore axis to obtain a porous metal fragment.
  • Approximately 10 pieces of the metal pieces are arranged and adhered to each other using an epoxy resin to prepare a sample for measuring the directionality of pores made of porous metal pieces as shown in the schematic perspective view of FIG.
  • Make this sample a suitable size (for example, Cut out with a disc of about 10 mm ⁇ ) and use for the following measurements.
  • the measured value of the sample surface ⁇ (that is, the surface through which water permeates in the direction in which the pore direction is maximum) is S max, and the sample surface B (that is, the direction in which water Calculate the pore directionality (Smax / Smin) with the measured value of the surface that transmits light as Sinin.
  • the porous metal used in the present invention preferably has the following mechanical strength characteristics in view of its durability and reliability (particularly important in the medical field).
  • the ratio ( ⁇ ) between the relative tensile strength ( ⁇ ) and the porosity ( ⁇ %) of the porous metal can be used as an index of mechanical strength.
  • ⁇ ⁇ ⁇ represented by the above formula is preferably 0.8 or more, more preferably 0.9 or more.
  • the indwelling device of the present invention typically includes, for example, artificial joints (FIG. 1), fracture fixing plates (FIG. 2), screws (FIG. 3), wires, and artificial dental roots (FIG. 4). Filling the cerebral aneurysm And a coil.
  • FIG. 1 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial joint.
  • This figure is an example of the so-called Changle type hip prosthesis.
  • This artificial hip joint consists of a pelvis-side socket 1 that uses high-density polyethylene (HDP), ultra-high-density polyethylene (UH-MWPE), etc. as artificial cartilage, and a metal apex (pole) on the femur side. It consists of a part 2 and a metal stem 3.
  • HDP high-density polyethylene
  • UH-MWPE ultra-high-density polyethylene
  • a porous metal for example, a porous titanium alloy
  • the weight of the base material is reduced, the impact force is absorbed, the affinity with the living body is increased, and infection is prevented. Benefits such as accelerating healing can be obtained.
  • FIGS. 2 (a) and 2 (b) are a schematic plan view and a schematic cross-sectional view, respectively, showing an example in which the indwelling device of the present invention is used as a fracture repair plate.
  • the fracture repair plate shown in FIG. 2 is an elongated member 4 that is slightly flat and has a desired number of holes 5.
  • a porous metal for example, a porous titanium alloy
  • absorption of impact force and stress prevents the fixing screw from being loosened, Affinity, and can have advantages such as prevention of infection and promotion of healing.
  • FIG. 3 is a schematic plan view showing an example in which the indwelling device of the present invention is in the form of a screw for repairing a fractured part.
  • the screw for repairing a fracture in FIG. 3 has a handle 7 having a screw thread 6.
  • the handle 7 is made of porous metal (for example, a porous titanium alloy)
  • the screws are prevented from being loosened by absorbing the impact force, and the infection is prevented by improving the affinity with the living body. Can gain benefits such as promoting healing You.
  • FIG. 4 is a schematic perspective view showing an example in which the indwelling device of the present invention is in the form of an artificial tooth root (implant).
  • the artificial tooth root in FIG. 4 has a fixture 11 for fixing the artificial tooth to the gum 10, an attachment 12 for supporting the engagement, and an upper part having a shape similar to the shape of a human tooth. Having structure 13.
  • a porous metal for example, a porous titanium alloy
  • advantages such as prevention of infection due to strong bonding with gingival fibers and promotion of healing can be obtained. it can.
  • the production method is not particularly limited as long as a porous metal having the above characteristics can be produced.
  • methods for producing a porous metal such as a fabrication method, a plating method, a powder metallurgy method, and a sputter deposition method, have been developed as described below.
  • Manufacturing methods include a melt foaming method, an interparticle infiltration method, and an investment method.
  • molten metal foaming method a physical method in which an inert gas or carbon dioxide gas is injected into the molten metal, agitated, foamed, and solidified, and a blowing agent such as a titanium hydride compound or a zirconium hydride compound is added to the molten metal.
  • a blowing agent such as a titanium hydride compound or a zirconium hydride compound
  • the interparticle infiltration method is a method in which molten metal is impregnated into gaps between small spheres packed in a mold and solidified, and hollow glass spheres or sodium chloride are often used for the small spheres. Small spheres made of sodium chloride After hardening, it can be dissolved with water.
  • the investment method the voids of the polyurethane foam are filled with a refractory slurry, dried, and then fired to form a mold. After forming the molten metal under reduced pressure, the mold is removed to produce a porous metal.
  • the porous metal having a large pore size can be produced by the interparticle permeation method or the impregnation method
  • the pore diameter of a porous metal suitable for the stent of the present invention that is, several ⁇ to several tens of It is relatively difficult to produce porous metal with a small pore size of ⁇ m.
  • the porous metal produced by the above method has a strong tendency that the pores become random and the mechanical properties deteriorate, and it is relatively difficult to process the obtained porous metal into a stent.
  • Draftite or the like is coated on the surface of the polyurethane foam skeleton by a chemical method, and this is used as a cathode. After nickel or the like is coated on the cathode in an electrolytic bath, the polyurethane foam is removed by firing to produce a porous metal. Also in this method, it is relatively difficult to produce a porous metal having a pore size suitable for the present invention and good mechanical strength.
  • a foaming agent is mixed with the slurry of the organic medium and the metal powder, foamed and solidified, and then fired.
  • the slurry foaming method is not used, and the slurry is not subjected to HIP (hot isostatic treatment) or CIP (cold isostatic treatment).
  • HIP hot isostatic treatment
  • CIP cold isostatic treatment
  • Pressure sintering method in which metal powder is sintered under pressure
  • sponge method in which polyurethane foam is immersed in a slurry of metal powder, dried, then pyrolyzed and sintered.
  • a sputtering method gold was placed on a water-cooled substrate in an inert gas.
  • the metal is sputter-deposited and a thin film is synthesized.
  • Such a thin film usually contains about 20 to 2000 ppm of an inert gas.
  • the production method of various porous metals or foamed metals has been outlined.
  • Another new method is the metal-gas method described later.
  • An open pore that can be suitably used for the porous metal for an indwelling device according to the present invention can be easily obtained, or the pore diameter is uniform, the pore directionality is small, and the pore diameter is as small as several ⁇ m to several hundred ⁇ m.
  • the metal-gas method can be particularly preferably used among the various methods described above.
  • the porous metal obtained by the metal-gas method is of an open type and can be easily provided with anisotropic pores. By making use of the features of such pores, it is possible to achieve weight reduction while maintaining mechanical strength. Further, as described above, the body tissue can penetrate into the pore, and a strong bonding layer can be obtained between the metal material and the surrounding tissue. Further, by filling the pores with a functional substance (drug or bioactive substance, etc.), it becomes easy to provide a sustained release function, and to impart healing, antibacterial and other functions to the indwelling device of the present invention. It becomes possible to do.
  • a functional substance drug or bioactive substance, etc.
  • a porous metal is produced by utilizing the difference in solubility of gas atoms between a molten state and a solidified state of the metal (Japanese Patent Laid-Open No. 10-82854, Nippei 1 0— 2 2 7 6 2 4 No., Japanese Patent Application No. 1 1 1 4 2 5 7 5, Japanese Patent Application No. 11-195 5 260; Production and Technology, Vol. 51, No. 3, page 60 (1 9 9 9)).
  • a gas hydrogen, oxygen or nitrogen
  • the hole diameter and pore direction can be controlled by the cooling rate and cooling method of the molten metal.
  • the pore formation is based on the precipitation of supersaturated gas atoms, it is extremely easy to make the shape of the pore cross section of the porous metal substantially circular, for example.
  • stress concentration does not occur around the pore at the time of deformation and a tensile stress is applied.
  • the “specific strength,” which is the stress divided by the effective cross-sectional area does not depend on porosity (eg, SK Hyun et al.
  • the pores of the porous metal by the metal-gas method can be easily formed into open pores (that is, the pore openings are on the surface of the porous metal).
  • Porous metal having such an open pore is a conventional porous metal. Unlike lath metal, it is easy to fill a drug or a physiologically active substance into the pore and release it slowly. .
  • the pores of the porous metal formed by the metal-gas method can be easily formed into a pore shape in which the directions of the pores are aligned in the axial direction, that is, a so-called “lotus root type pore”. It has been demonstrated that such a lotus root type pore has higher torsional strength and axial compressive strength than a solid (no pore) rod-shaped sample.
  • Material Selection pp. 149-153, translated by Junichi Kaneko and Masahisa Otsuka, published by Uchida Ritsuruho, 1977.
  • FIG. 9 is a graph showing an example of the relationship between porosity and ⁇ / ⁇ 0 (relative tensile strength) of “Rotkon type” porous copper manufactured using the metal-gas method. As is clear from this graph, the above-mentioned “lencon-type” porous copper is superior to conventional sintered or foamed metal in strength at the same porosity.
  • the material of the porous metal is not particularly limited as long as a porous metal having the above-described characteristics can be manufactured.
  • a porous metal having the above-described characteristics can be manufactured.
  • iron, nickele, anorenium, copper, magnesium, konorenot, tungsten, manganese, chromium, beryllium, titanium, silver, gold and alloys thereof for example, iron, nickele, anorenium, copper, magnesium, konorenot, tungsten, manganese, chromium, beryllium, titanium, silver, gold and alloys thereof
  • a modified layer for example, a solid solution strengthening layer or a ceramic layer
  • a modified layer may be formed on the inner surface of the pore of the porous metal as needed.
  • the strength tensile strength, compressive strength, bending strength, etc.
  • the porous metal in the present invention can be produced, for example, by utilizing the difference in the solubility of gas atoms in a molten state and a solidified state of a metal in a metal-gas system. Gas method).
  • the solubility of gas atoms such as hydrogen, oxygen, and nitrogen in the metal decreases, and the gas phase separates from the metal phase to form pores.
  • the solid solution strengthening layer can be easily formed by diffusing the gas atoms from the inner wall of the pore into the metal. By forming the solid solution strengthening layer, the hardness and the like of the inner surface of the pore can be improved.
  • a ceramic is formed on the inner surface of the porous metal pore by a known ceramic forming method. Layers can be formed.
  • a ceramic forming method a chemical vapor deposition method (chemical vapor deposition) or a physical vapor deposition method (physical vapor deposition; for example, ion implantation method) can be preferably used. is there.
  • a ceramic such as titanium nitride (TiN) or titanium carpide (TiC) is used.
  • TiN or TiC is formed on the inner surface of a porous metal by using titanium as an evaporation source and using nitrogen or acetylene as a reaction gas element by an ion plating method. It is possible.
  • the thickness of the ceramic layer is adjusted to 100 by controlling the vapor deposition conditions. It can be controlled in the range of A (Angstrom) to several ⁇ m.
  • the method for imparting the indwelling device shape to the porous metal described above is not particularly limited, and a known method can be used.
  • a supersaturated gas is precipitated in a solid phase in a process of dissolving a gas in a molten metal material, and then solidifying and transforming the solid into a solid.
  • Porous metal is produced by using this property, and used as a base material for indwelling devices.
  • Examples of a method for producing an indwelling device using the porous metal include a method using a linear porous metal and a method of finishing a desired shape by cutting a plate-shaped or rod-shaped porous metal.
  • Fracture fixation wires, cerebral aneurysm ligation clips, cerebral aneurysm filling coils, etc. are also produced from the former, and fracture fixation plates, screws, artificial dental roots, etc. are made by the latter method. it can.
  • All or a part of the metal part constituting the indwelling device of the present invention can be basically made of a porous metal.
  • a portion particularly preferably constituted by a porous metal is exemplified as follows.
  • Fracture fixation plate (as shown in Fig. 2, etc.): Plate body 4 Fracture fixing screw (as shown in Fig. 2, etc.): Screw with screw thread 6 Body 7
  • Fracture fixation wire Wire body
  • Cerebral aneurysm filling coil Coil body
  • the method for imparting the stent shape to the porous metal is not particularly limited, and a known method can be used.
  • a supersaturated gas is precipitated in a solid phase in a process of dissolving a gas in a molten metal material, and then solidifying and transforming the solid into a solid.
  • the porous metal is produced by using the property that the metal is used as the base material of the stent.
  • Examples of a method for producing a stent using the porous metal include a method using a linear porous metal and a method of finishing a cylindrical porous metal into a desired shape by cutting.
  • a coil stent is manufactured from the former, and a slotted tube stent is manufactured from the latter.
  • FIG. 10 is a schematic cross-sectional view showing an example of an apparatus for producing a linear porous metal.
  • a ceramic crucible 21 having a nozzle 21 a is filled with a material such as stainless steel, tantalum, titanium, an alloy of titanium and nickel (Nitinol), and high-frequency heating 2 2 Heat is applied from the periphery by such means as heating and melting.
  • the atmosphere is hydrogen, oxygen, nitrogen, or a mixed gas of them with an inert gas such as argon or helium.
  • the solidification rate can be controlled by controlling the temperature and flow rate of the cooling medium circulating in the cooling section, or by installing a heating section in the cooling section 25, whereby the pores can be controlled. It is possible to freely control the size, length (pore aspect ratio), porosity, and angle between the linear busbar and the pore growth direction. Since the surface of the porous fine metal wire 26 generated in this manner has an extremely high cooling rate, pores cannot normally be generated on the surface of the fine wire, and a nonporous surface is formed. . For this purpose, if necessary, the non-polar surface of the fine wire may be removed by a chemical polishing method such as corrosion etching using an acid solution, or a physical or mechanical polishing method such as sand polishing or mechanical cutting.
  • a chemical polishing method such as corrosion etching using an acid solution
  • a physical or mechanical polishing method such as sand polishing or mechanical cutting.
  • the final shape of the porous fine metal wire 26 is, for example, as shown in Fig. 11, with pores exposed on the surface and growing with a slight inclination in the direction of the fine wire bus. It will be.
  • drawing plastic working may be performed as necessary to form a fine wire having a uniform diameter. This process is not merely to make the thickness uniform, but also to introduce new plasticity into the thin wire 26 to refine the crystal grains. There is an advantage that the strength of the fine wire can be enhanced by introducing the stub.
  • FIG. 12 is a schematic cross-sectional view showing an example of an apparatus for producing a cylindrical porous metal.
  • a ceramic crucible 32 is filled with starting materials 31a, such as stainless steel, tantalum, titanium, and an alloy of titanium and nickel (Nitinol), and a high-frequency heating coil 33 Heat is melted by applying heat from the surroundings.
  • the crucible 32 is surrounded by a heat insulator 34, a heat shield 35, and a pressure vessel 36.
  • molten metal (or alloy) 3 is used as atmosphere 31 c using hydrogen, oxygen, nitrogen or a mixed gas thereof with an inert gas such as argon or helium.
  • the above-prepared porcelain metal produced as described above is cut into a plate shape or a rod shape and cut and plastically processed.
  • it can be rolled at the stage of cutting out into a porcelain porous metal or a plate or a rod, and then subjected to plastic working to refine the crystal grains and strengthen the base material by plastic strain. It is.
  • the porous metal manufacturing process metal- In the gas method, gas atoms such as oxygen or nitrogen usually react with the metal to form a solid solution oxygen or nitrogen-enriched layer on the inner surface of the pore of the porous metal.
  • gas atoms such as oxygen or nitrogen usually react with the metal to form a solid solution oxygen or nitrogen-enriched layer on the inner surface of the pore of the porous metal.
  • the inner surface of the pore of the porous metal is formed using a chemical vapor deposition method or a physical vapor deposition method (such as an ion plantation method).
  • a ceramic layer such as titanium nitride or titanium carbide having excellent hardness, a porous metal having further excellent mechanical properties can be obtained.
  • the growth amount and morphology of the pores in the porous metal are determined by the melting temperature, the melting point, Parameters such as gas pressure, solidification gas pressure, cooling temperature, solidification cooling rate, and mixing volume ratio with inert gas-pressure can be freely and accurately controlled and determined.
  • the graph in Fig. 13 shows that one-way multicore pores are formed by solidifying nitrogen gas into iron melted at about 650 ° C under the pressure of a mixture of nitrogen and argon, respectively. is represented by the relationship between the porosity of the porous iron was produced (%) and nitrogen gas partial pressure (P- N 2) and argon gas partial ⁇ (P- a r).
  • Figures 14 to 17 show optical micrographs (magnification: 2.6 times) of cross sections of porous iron obtained by the ratio of the partial pressures of nitrogen gas and argon gas shown in the graph of Figure 13 respectively. It is. According to these figures, the porosity changes depending on the ratio of the partial pressure of nitrogen gas to the partial pressure of argon gas, and the porosity increases as the nitrogen gas pressure increases relative to the argon gas pressure. You can understand that.
  • the in-vivo indwelling device of the present invention comprising the above-described porous metal can be filled with various nonmetallic substances, if necessary.
  • a nonmetallic substance a functional material capable of exerting various functions, and imparting useful functions to the in-vivo indwelling device by carrying it in the pore and releasing it or releasing it slowly can do.
  • the nonmetallic substance to be filled in the pores of the porous metal is not particularly limited as long as the function of the indwelling device of the present invention comprising a porous metal is not substantially impaired.
  • the nonmetallic substance preferably contains an organic substance from the viewpoint of easy filling into the pores and easy provision of functionality.
  • the indwelling device of the present invention can carry a drug or a physiologically active substance and / or sustained release.
  • the drug or bioactive substance to be filled in the pore, and one or more known drugs or bioactive substances can be appropriately selected or used in combination.
  • drugs or physiologically active substances include thrombus formation inhibition, thrombolysis, platelet adhesion / aggregation inhibition, infection prevention, anticancer properties, growth inhibition of fibroblasts / smooth muscle cells, vascular endothelium, etc. Substances having the ability to promote proliferation of cells and the like can be mentioned.
  • the bone cells or the like of the patient itself can be suitably used as necessary for the plate for fixing a fractured part or the artificial dental root.
  • a stem cell capable of differentiating into a vascular endothelial cell or a vascular endothelial cell is preferably used to promote vascular endothelialization.
  • the above-mentioned drug or physiologically active substance is filled in the pores of the indwelling device of the present invention made of porous metal
  • a drug or a physiologically active substance is selected depending on the solubility of the drug or the physiologically active substance to be filled in blood, the molecular weight, the physiologically active concentration, the release period, and the like.
  • suitable polymer materials there is a polymer material having biodegradability.
  • biodegradable polymer material examples include biodegradable polyesters typified by polydicalic acid, polylactic acid, various polylactones, and the like.
  • drug or physiologically active substance incorporated in the high molecular material elutes from the surface of the material, so that the porous polymer material, in particular, the hydrogel (a hydrous liquid to be retained inside is substantially lost) Or a so-called “xerogel” state) or a polymer having a mouth-opening gel-forming property.
  • the gel for the mouth opening include natural gels such as collagen gel, gelatin gel, fiprimin gel, matrigel, genole alginate, chitosan gel, hyaluronic acid gel and various synthetic polymer hydrogels. Is mentioned.
  • a polymer material for immobilizing cells for example, bone cells for promoting bone formation or vascular endothelial cells for promoting vascular endothelialization
  • the activity of cells inside the polymer material is maintained. It is highly preferred that nutrients can be easily replenished and waste products removed so that they can be divided and propagated.
  • a hide-mouth gel can be particularly preferably used as a polymer material for immobilizing cells.
  • the above-mentioned natural product hydrogel, and a gelling type thermoreversible individual dydrogene at the time of heating, which becomes a solution state at a low temperature and a gel state at a high temperature Yoshioka, H.
  • the method of filling a nonmetallic substance for example, a drug, a physiologically active substance or a cell
  • a nonmetallic substance for example, a drug, a physiologically active substance or a cell
  • a high molecular material as necessary is not particularly limited. It can be appropriately selected from known methods or used in combination.
  • a method of combining a drug or a physiologically active substance with a polymer material a mixed solution in which both are dissolved or dispersed in water or an organic solvent is prepared, and the mixed solution is prepared from the porous metal of the present invention.
  • the most common method is to immerse the indwelling device.
  • the air in the pores of the indwelling device is replaced with a mixed solution under negative pressure, and the indwelling device is taken out and dried to remove water or an organic solvent.
  • Non-metallic material can be filled into the pores of the detention tool.
  • the cells are dispersed in a solution containing a hydrogel-forming polymer, and the dispersion is used in a device for indwelling the body. After the introduction into the pore, by changing the pH or the temperature, the hydrogel-forming polymer can be gelled and the cells can be immobilized in the gel.
  • alginic acid gel cells are dispersed in a medium solution of sodium alginate, and the dispersion is introduced into the pores of the indwelling device, and then, for example, contacted with a concentrated calcium chloride solution.
  • the alginate soda can be gelled and the cells can be immobilized in the pore.
  • cells are dispersed in a solution state in which the hydrogel-forming polymer is dissolved at a low temperature, and the cell dispersion is placed in a pore of an indwelling device. After filling inside, The cells can be immobilized by increasing the degree of gelation of the polymer having a gel-forming mouth opening to a higher degree.
  • the sol-gel transition temperature of the gelled thermoreversible hide opening gel at the time of temperature rise is preferably within the physiological temperature range of cells.
  • the indwelling device according to the present invention not only has excellent strength and lightness due to the porous metallic material constituting the device, but also has a remarkably increased contact area with internal tissues. Sufficient bonding strength can be easily obtained.
  • the indwelling device not only has excellent mechanical strength but also exhibits toughness similar to hard tissue in the body. Becomes easier.
  • the indwelling device of the present invention having the above structure since the metal material constituting the device is porous (especially in the case of the above-described anisotropic pore structure), the in-vivo tissue can easily enter the inside thereof. It is easy to strengthen the bond between the metal material and the surrounding body tissue.
  • the size of the pore can be controlled so that the body tissue can enter the pore, the degree of penetration of the body tissue can be controlled by the size of the pore.
  • the in-vivo indwelling device of the present invention has high functions (for example, healing promoting action, Antibacterial action, anti-hemolytic action, thrombus forming action, etc.).
  • the stent formed by the porous metal can prevent the stent itself from being weakened or peeling the coating material from the stent main body as much as possible, and the non-metal can be contained in the pores of the porous metal constituting the stent. It is very easy to fill the substance. Therefore, by filling various functional substances such as organic substances as the non-metallic substance, it is extremely easy to impart a desired function to the whole indwelling device (stain or the like) of the present invention.
  • the porous metal itself constituting the stent has a porous structure, even when the stent is filled with a nonmetallic substance, the stent itself as in the case of a polymer material is used. This makes it possible to suppress the weakening of the coating material and the peeling off of the coating substance from the stent body as much as possible. In this case, it becomes possible to release these substances from the pores. Alternatively, it is also possible to fill the pores with vascular endothelial cells or stem cells supported on hydrogel or the like.
  • the open pores and the orientation are uniform. It is possible to easily obtain pores and / or pores having a solid solution strengthening layer or a ceramic layer having excellent hardness on the inner surface. Therefore, as a stent formed from the porous metal, a stent having excellent mechanical properties, preventing recoil of a blood vessel wall, etc., and exhibiting excellent durability against repeated stretching and contraction movements of a blood vessel wall, etc., can be easily obtained. Obtainable.

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  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Transplantation (AREA)
  • Neurology (AREA)
  • Ceramic Engineering (AREA)
  • Dentistry (AREA)
  • Prostheses (AREA)
  • Materials For Medical Uses (AREA)
  • Dental Prosthetics (AREA)
  • Surgical Instruments (AREA)

Abstract

Instrument à demeure de faible poids qui possède une excellente propriété mécanique et d'excellentes capacités pour joindre in vivo les tissus. Au moins dans une de ses parties, il contient une partie métallique composée au moins partiellement d'un métal poreux.
PCT/JP2001/000202 2000-12-21 2001-01-15 Instrument a demeure WO2002049548A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001225537A AU2001225537A1 (en) 2000-12-21 2001-01-15 Indwelling instrument

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000389309A JP2002306518A (ja) 2000-12-21 2000-12-21 体内留置用具
JP2000/389309 2000-12-21

Publications (1)

Publication Number Publication Date
WO2002049548A1 true WO2002049548A1 (fr) 2002-06-27

Family

ID=18855890

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2001/000202 WO2002049548A1 (fr) 2000-12-21 2001-01-15 Instrument a demeure

Country Status (3)

Country Link
JP (1) JP2002306518A (fr)
AU (1) AU2001225537A1 (fr)
WO (1) WO2002049548A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109069188A (zh) * 2016-02-29 2018-12-21 美敦力索发摩尔丹耐克有限公司 用于抗菌性体内植入装置的固定螺钉
US11364122B2 (en) 2017-03-10 2022-06-21 Vestlandets Innovasjonsselskap As Tissue engineering scaffolds

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004261218A (ja) * 2003-02-07 2004-09-24 Yasuhiko Tabata 血管塞栓用組成物
CA2599416A1 (fr) * 2005-02-23 2006-08-31 Small Bone Innovations, Inc. Implants osseux
JP4723937B2 (ja) * 2005-07-13 2011-07-13 株式会社カネカ 細胞の播種方法

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US4360023A (en) * 1976-08-17 1982-11-23 Mizuho Ika Kogyo Kabushiki Kaisha Cerebral aneurysm clip
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WO1986003671A1 (fr) * 1984-12-14 1986-07-03 Klaus Draenert Materiau de remplacement d'os et son utilisation
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WO1989004674A1 (fr) * 1987-11-26 1989-06-01 Biocon Oy Articles destines a entrer en contact avec des tissus du corps et contenant un agent anti-microbien
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JPH1147171A (ja) * 1997-07-31 1999-02-23 Kyocera Corp 人工補綴部材
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US6007573A (en) * 1996-09-18 1999-12-28 Microtherapeutics, Inc. Intracranial stent and method of use
WO2000064504A2 (fr) * 1999-04-28 2000-11-02 Bruce Medical Ab Corps destine a permettre l'interposition et la croissance de tissu osseux et/ou de tissu conjonctif, et procede de fabrication

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3855638A (en) * 1970-06-04 1974-12-24 Ontario Research Foundation Surgical prosthetic device with porous metal coating
US3707006A (en) * 1970-08-26 1972-12-26 Gulf Oil Corp Orthopedic device for repair or replacement of bone
US4360023A (en) * 1976-08-17 1982-11-23 Mizuho Ika Kogyo Kabushiki Kaisha Cerebral aneurysm clip
US4781721A (en) * 1981-02-25 1988-11-01 S+G Implants Bone-graft material and method of manufacture
US4542539A (en) * 1982-03-12 1985-09-24 Artech Corp. Surgical implant having a graded porous coating
WO1986003671A1 (fr) * 1984-12-14 1986-07-03 Klaus Draenert Materiau de remplacement d'os et son utilisation
US4976738A (en) * 1985-01-09 1990-12-11 Sulzer Brothers Limited Porous metal overlay for an implant surface
WO1989004674A1 (fr) * 1987-11-26 1989-06-01 Biocon Oy Articles destines a entrer en contact avec des tissus du corps et contenant un agent anti-microbien
JPH01265954A (ja) * 1988-04-15 1989-10-24 Kobe Steel Ltd 代替骨
WO1990008520A1 (fr) * 1989-02-06 1990-08-09 The Trustees Of The University Of Pennsylvania Ceramique de phosphate de calcium activant la calcification des tissus osseux
WO1991006324A1 (fr) * 1989-11-03 1991-05-16 Karlheinz Schmidt Complexe de substance active pour l'obtention d'elements biologiques, notamment d'organes pour des etres vivants, son procede de fabrication et son utilisation
JPH04141163A (ja) * 1990-10-01 1992-05-14 Kawasaki Steel Corp 骨親和性に優れた金属多孔質材料およびその製造方法
US5681572A (en) * 1991-10-18 1997-10-28 Seare, Jr.; William J. Porous material product and process
US5498302A (en) * 1992-02-07 1996-03-12 Smith & Nephew Richards, Inc. Surface hardened biocompatible metallic medical implants
US5702446A (en) * 1992-11-09 1997-12-30 Board Of Regents, The University Of Texas System Bone prosthesis
JPH07184987A (ja) * 1993-12-27 1995-07-25 Kyocera Corp 人工補綴部材
US5449832A (en) * 1994-10-05 1995-09-12 Air Products And Chemicals, Inc. Process for storage and transport of toluenediamine
US6007573A (en) * 1996-09-18 1999-12-28 Microtherapeutics, Inc. Intracranial stent and method of use
US5954724A (en) * 1997-03-27 1999-09-21 Davidson; James A. Titanium molybdenum hafnium alloys for medical implants and devices
US5843172A (en) * 1997-04-15 1998-12-01 Advanced Cardiovascular Systems, Inc. Porous medicated stent
WO1998047447A1 (fr) * 1997-04-23 1998-10-29 Dubrul William R Extenseur bifurque et systeme distal de protection
JPH1147171A (ja) * 1997-07-31 1999-02-23 Kyocera Corp 人工補綴部材
WO1999016478A1 (fr) * 1997-10-01 1999-04-08 Phillips-Origen Ceramic Technology, Llc Substituts d'os
WO2000064504A2 (fr) * 1999-04-28 2000-11-02 Bruce Medical Ab Corps destine a permettre l'interposition et la croissance de tissu osseux et/ou de tissu conjonctif, et procede de fabrication

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109069188A (zh) * 2016-02-29 2018-12-21 美敦力索发摩尔丹耐克有限公司 用于抗菌性体内植入装置的固定螺钉
US11364122B2 (en) 2017-03-10 2022-06-21 Vestlandets Innovasjonsselskap As Tissue engineering scaffolds

Also Published As

Publication number Publication date
AU2001225537A1 (en) 2002-07-01
JP2002306518A (ja) 2002-10-22

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