WO2003070289A1 - Element d'articulation artificielle realise en materiau polymere - Google Patents
Element d'articulation artificielle realise en materiau polymere Download PDFInfo
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- WO2003070289A1 WO2003070289A1 PCT/JP2003/001750 JP0301750W WO03070289A1 WO 2003070289 A1 WO2003070289 A1 WO 2003070289A1 JP 0301750 W JP0301750 W JP 0301750W WO 03070289 A1 WO03070289 A1 WO 03070289A1
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- polymer
- artificial joint
- joint member
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- 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
-
- 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
-
- 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
- A61F2/46—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
- A61F2/468—Testing instruments for artificial joints
-
- 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
- A61L27/34—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- 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
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- 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
- A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
- A61F2002/30673—Lubricating means, e.g. synovial pocket
-
- 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
- A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
- A61F2002/30682—Means for preventing migration of particles released by the joint, e.g. wear debris or cement particles
- A61F2002/30685—Means for reducing or preventing the generation of wear particulates
-
- 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
- A61F2002/30934—Special articulating surfaces
-
- 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
- A61F2/3609—Femoral heads or necks; Connections of endoprosthetic heads or necks to endoprosthetic femoral shafts
- A61F2002/3611—Heads or epiphyseal parts of femur
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00011—Metals or alloys
- A61F2310/00017—Iron- or Fe-based alloys, e.g. stainless steel
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00011—Metals or alloys
- A61F2310/00029—Cobalt-based alloys, e.g. Co-Cr alloys or Vitallium
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00179—Ceramics or ceramic-like structures
- A61F2310/00185—Ceramics or ceramic-like structures based on metal oxides
- A61F2310/00203—Ceramics or ceramic-like structures based on metal oxides containing alumina or aluminium oxide
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00179—Ceramics or ceramic-like structures
- A61F2310/00185—Ceramics or ceramic-like structures based on metal oxides
- A61F2310/00239—Ceramics or ceramic-like structures based on metal oxides containing zirconia or zirconium oxide ZrO2
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/24—Materials or treatment for tissue regeneration for joint reconstruction
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
- B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
- B29K2995/0037—Other properties
- B29K2995/0087—Wear resistance
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
- B29L2031/00—Other particular articles
- B29L2031/753—Medical equipment; Accessories therefor
- B29L2031/7532—Artificial members, protheses
Definitions
- the present invention relates to an artificial joint member made of a polymer material, and more particularly to an artificial joint member made of a high molecular material that can maintain a good lubrication state of a sliding portion for a long period of time.
- the structure in order to provide a good lubrication state to the artificial joint sliding part, the structure must be a fine beard like cilia on the joint material sliding surface. It is considered that a structure in which the substances are arranged and the ciliary substance can hold a bodily fluid as a lubricating liquid is preferable. However, it is difficult to artificially reproduce such a state, and it is extremely difficult to maintain the state for a long period of time, and it has not yet been realized.
- soft materials such as resin and hard materials such as metal are used in combination as artificial joint members such as the head and acetabular joint.
- metal materials such as stainless steel, cobalt chromium alloy, and titanium alloy are used.
- Artificial joints that combine the bone head members used and acetabular resins made of resin such as ultrahigh molecular weight polyethylene are used in tens of thousands of operations annually in Japan alone. This replacement of the prosthesis frees the patient from pain and bedridden conditions and improves the quality of life before living a healthy life.
- the friction between the metal member and the resin member frequently occurs at the sliding portion due to the operation of daily life. Wear progresses, especially on the resin side of the artificial joint. Wear particles such as ultra-high molecular weight polyethylene generated by such abrasion tend to cause the dissolution of the bone, and when a part of the bone dissolves, the adhesive force between the artificial joint member and the bone is weakened. So-called loosening occurs, making it difficult for the joint to function properly.
- the normal wear of the ultra-high molecular weight polyethylene is about 0.1 to 0.2 mm per year, and there is no problem for a while after the replacement operation, but after about 5 years, the loosening occurs. It becomes so severe that it is necessary to replace it with a new artificial joint member.
- the head of the Kontrol Krom and the Kovarto Krom With the combination of alloy cups (acetabular), the abrasion powder generated by friction between the Cobalt chromium alloys is inherently cytotoxic, so there is concern about long-term use and safety.
- alumina head and aluminum cap may be damaged during surgery or post-operative use because the alumina material is a brittle material. In that case, further improvement is necessary.
- these hard members are rigid bodies having poor elasticity and do not have a cushioning function as in the case of the ultrahigh molecular weight polyethylene, they do not have a buffering effect against external force and are directly loaded on the bone, which is preferable. Absent.
- the present invention has been made in view of such circumstances, and an object of the present invention is to suppress the generation of abrasion powder by suppressing the friction of a sliding portion even in a repetitive daily operation.
- An object of the present invention is to provide an artificial joint member made of a polymer material which can be used for a long period of time with a shock absorbing function. Disclosure of the invention
- the artificial joint member made of a polymer material according to the present invention is characterized in that the sliding surface of the artificial joint member formed of a polymer material is made of a polymer having a phosphorylcholine group.
- the following are examples of the preferred embodiment.
- the phosphorylcholine group is bonded to a polymer substance through a (meth) acryloyloxyalkyl group.
- the polymerizable substance having a phosphorylcholine group in the polymer substance is preferable.
- Those with grafted monomers are chemically stable, Desirable.
- ultrahigh molecular weight polyethylene having a molecular weight of 100,000 or more is preferably used. Further, it is preferable to use a crosslinked material as the polymer substance because excellent abrasion resistance can be ensured.
- the present invention includes an artificial joint obtained by using such an artificial joint member made of a polymer material.
- polymer material refers to the base portion of the artificial joint member, and the “polymer material” refers to the “polymer material” and the “artificial joint comprising a polymer having a phosphorylcholine group”. It refers to the entire artificial joint member together with the “sliding surface of the member”.
- FIG. 1 is a perspective sectional view schematically showing a biological membrane.
- FIG. 2 is a schematic side view of the rotational oscillating friction test apparatus used in Example I.
- Fig. 3 is a graph showing the change in friction torque when pure water is dropped depending on whether or not the MPC polymer is formed.
- Fig. 4 is a graph showing the relationship between the sliding speed and the friction torque depending on whether or not the MPC polymer is formed.
- Figure 5 shows a schematic side view of the rotary oscillation friction tester used in Example IV.
- FIG. 5 shows a schematic side view of the rotary oscillation friction tester used in Example IV.
- Figure 6 is a graph showing the relationship between the number of rotating cycles and the wear of the ultra-high molecular weight polyethylene cup, with or without crosslinking treatment.
- the present inventors have found that when a polymer material having a better shock absorbing function than a hard material such as a metal is used as an artificial joint member, the friction of a sliding portion is reduced. From various angles to study the surface modification of polymer materials used in artificial joints so that the amount of ash is suppressed as much as possible and the abrasion powder generated by rubbing becomes inactive against cells that exert immune functions was done. As a result, they have found that a compound having a chemical structure similar to that of cells constituting a living tissue may be formed on the surface of a polymer substance, and have reached the present invention.
- the artificial joint member made of a polymer material according to the present invention will be described in detail below.
- the biomembrane that forms the surface of the aggregate is an aggregate of phospholipid molecules, and the surface is microscopically covered with phosphorylcholine groups.
- the compound having the phosphorylcholine group has the same chemical structure as the cells constituting the living tissue, even if abrasion powder is generated due to friction, it has a bad effect on the human body. Shows good biocompatibility without any problems.
- the present invention achieves the above effects by forming the sliding surface of the artificial joint member formed of a polymer substance with a polymer having a phosphorylcholine group as described above.
- the phosphorylcholine group is chemically bonded to the polymer via a (meth) acryloyloxyalkyl group. It is desirable because it is chemically stable and easily formed by the polymerization method described below.
- a method for obtaining a structure in which a phosphorylcholine group is chemically bonded to a polymer substance via a (meth) acryloyloxyalkyl group is to directly convert the monomer to the polymer substance.
- a method of synthesizing in advance, coating the polymer material, and then immobilizing it on the surface of the polymer material by a cross-linking reaction can be mentioned.
- a method of bonding a polymerizable monomer having a polymer can modify only the surface of the polymer without deteriorating the performance such as the strength of the polymer, and the bonding portion is chemically bonded. Stable Further, it is preferable that a large amount of phosphorylcholine group is formed on the sliding surface of the artificial joint member so that the lubricating liquid can be sufficiently retained.
- Examples of the polymerizable monomer having a phosphorylcholine group include, for example, 2-methylcycloyloxetylphosphorylcoline and 2-acryloxyloxetylphosphoryl.
- Lilycoline, 41-methacryloyloxybutylphosphorylcoline, 6_methacryloyloxyhexylphosphorylcoline, ⁇ —methacryloyloxy Tylene phosphoryl choline, 4-styryloxybutyl phosphoryl choline, and the like can be used.
- 2 methacryloyloxhetyl phosphoryl choline represented by the following chemical formula 1 is particularly preferred.
- MPC phosphorylcholine group and polymerizable methacrylic acid unit, and can easily obtain a high molecular weight polymer by radical polymerization. It is preferable because it can be
- MPC polymer 2-methacryloyloxetylphosphorylcholine
- MPC polymer 2-methacryloyloxetylphosphorylcholine
- a large amount of phosphorylcholine groups can be formed on the sliding surface of the artificial joint member by binding to a molecular substance. Since the surface formed by the MPC polymer has a form similar to that of the biological membrane as shown in FIG. 1, it is possible to sufficiently hold the lubricating liquid and suppress the friction, and It is desirable because its reactivity with biological components and cells is small.
- another vinyl compound or the like may be allowed to coexist at the time of the above-mentioned graphitization to form a copolymer with a phosphorylcholine-containing compound.
- the polymer material in the case where the sliding surface of the artificial joint member formed of a polymer material is formed of a polymer having a phosphorylcholine group, the polymer material may be modified to include phosphorylcoline. Examples thereof include those in which a homopolymer or a copolymer of a phosphorus-containing compound is coated.
- a (meth) acryloyloxyalkylphosphorylcholine which is a polymerizable compound that is easy to form a polymer
- the phosphorylcholine-containing compound for example, for example, 2—methacrylic irilexoxyethyl phosphoryl J recorin, 2—acryloyloxhetyl phosphoryl chololin, 4_metacryloyriloleoxybutyl Phosphorylcorin, 6—methacryloyloxyhexylphosphorylcorin, ⁇ —methylacryloxyethylenephosphoricolin, 4—styroxybutylphosphorylcorin, etc.
- a solvent such as phenol, tetrahydrofuran, etc.
- the sliding surface of the artificial joint member formed of a polymer material is formed of a polymer having a phosphorylcholine group.
- a blend method in which the phosphorylcholine-containing compound is kneaded in advance with a polymer substance such as ultra-high molecular weight polyethylene and then molded may be employed.
- ultra-high molecular weight polyethylene is desirable to use as the polymer substance serving as the base of the artificial joint member according to the present invention.
- the ultra-high molecular weight polyethylene is preferably used in a molecular weight of 100,000 or more, because sliding wear is less likely to occur as the molecular weight is higher, and more preferably, in a molecular weight of 300,000 or more. is there.
- a cross-linked material As the above-mentioned polymer substance because excellent abrasion resistance can be ensured.
- a specific method of the cross-linking treatment a known method may be adopted. For example, X-ray irradiation, gamma ray irradiation, electron beam irradiation, etc., as well as micro-wave crosslinking or ultrasonic crosslinking And the like.
- the present invention does not specify the detailed conditions for the graft polymerization.
- the present invention may be performed by irradiating ultraviolet light having a wavelength of 300 to 400 nm as shown in Examples described later.
- a mercapto compound is adsorbed on a polymer substance, and then the monomer is polymerized using a radical generator in a solvent in which the compound is not eluted, and the aromatic nitrate is adsorbed on the polymer radical generated.
- capturing with a compound or a mercapto compound it can be carried out by a method of graphing a polymer chain on the surface of a polymer substance.
- both the head and acetabular joint of the present invention are used.
- one of the head and the acetabulum is used as the artificial joint member of the present invention, and the other is made of a metal such as stainless steel or cobalt chrome alloy, or a ceramic such as alumina / zirconia. It may be a member made of such as.
- only the sliding portion of the artificial joint member of the head and / or acetabular is defined as the artificial joint member of the present invention, and the other portions are made of other polymer materials, the above metals, ceramics, or the like. May be of a composite form.
- the phosphoryl alcohol is applied to the surface (one side only) of ultra high molecular weight polyethylene timber (cross section: 20 mm X 20 mm, length: 50 mm) having a molecular weight of 300 to 500,000 by the following method.
- a polymer layer having a functional group was formed.
- the ultra-high molecular weight polyethylene timber was immersed in an aceto- ene solution containing benzophenone (1.0 OgZdL) for 30 seconds, then immediately pulled up and the solvent was removed at room temperature.
- the MPC polymer-formed surface of the obtained test piece was examined with an X-ray photoelectron spectrometer, and a signal of 399 eV of nitrogen atoms and a signal of 133 eV of phosphorus atoms were detected. As a result, it was confirmed that the phosphorylcholine group in MPC was present on the surface of the polymer material.
- Table 2 shows that when the MPC polymer was formed, the coefficient of friction was small and lubricity was significantly improved. This is because the formation of a few molecular layers of MPC polymer on the surface increases the hydrophilicity, and a layer with a high free water content of up to 90% is formed on the surface. Conceivable.
- a rotational oscillating wear test was performed using an ultra-high molecular weight polyethylene force on the acetabular and a stainless steel sphere on the bone head.
- Figure 2 shows the device used for the rotational oscillating friction test.
- the main shaft B which freely rotates along the main shaft X—X, has a diameter of 12.10 m.
- An ultra-high molecular weight polyethylene cup (molecular weight 300,000 to 500,000) 1 having a hemispherical concave portion 2 of m is attached, while a stainless steel (SUS316) diameter of 12.00 is attached.
- the steel ball 3 is attached to the jig, and the support shaft of the steel ball 3 is opposed to the main axis X—X while the steel ball 3 is pressed against the inner wall concave surface 2 of the cup 1 by the force F by air pressure. Then, it is rotated at an angle of 6 °.
- the steel ball 3 is driven by a motor (not shown) whose rotation speed can be adjusted.
- An arm for measuring the friction torque is attached to the main shaft B, so that the friction torque when the main shaft B is about to rotate by the friction force generated by the rotation of the steel ball 3 can be measured.
- the surface roughness of the steel ball 3 is constant at RaO.02 m, and the cup 1 made of ultra-high molecular weight polyethylene has a concave surface with MPC polymer formed by the method described above. An untreated product in which no MPC polymer was formed was used. The following experiments (1) to (3) were performed using such an apparatus.
- ultra-high molecular weight polyethylene with MPC polymer formed In the cup it can be seen that the friction torque increases from the start of sliding, but when pure water is supplied halfway, the friction torque sharply decreases and thereafter maintains a low torque. This is presumably because pure water is retained in the formed MPC polymer, which ensures a good lubrication state for a long time, and reduces friction.
- the acetabular was applied to the crosslinked ultra-high molecular weight polyethylene cup or to the ultra-high molecular weight polyethylene cup without the treatment, and the MPC polymer was used as described above.
- Rotational oscillating wear test was performed using a Cobalt chrome alloy (22 mm in diameter) for the head of the head.
- the cross-linking treatment was performed by irradiating an ultra-high molecular weight polyethylene cup with an A-line having a strength of 5 Mrad for 320 minutes.
- FIG. 5 shows a schematic side view of the device.
- an ultra-high molecular weight polyethylene cup 11 was fixed on a face plate attached at 45 ° to the lower spindle XI in Fig. 5, and the upper spindle XII_XII
- the head 12 attached above was pressed against the concave portion of the cup 11, and the lower spindle XIII—XIII was rotated to measure the wear of the cup 11.
- the pressing load was set to 274 N (280 kgf), the rotation cycle was set to 1 Hz, and the load fluctuation for one cycle was adjusted to the walking curve of Pou1.
- bovine serum in which the above-mentioned cup 11 and head 12 were controlled to a constant temperature of 37 X: (25% by mass) and subjected to the abrasion test.
- the above bovine serum was replaced every 500,000 rotation cycles.
- the present invention is configured as described above, and it is possible to provide an artificial joint member that maintains a good lubricating state for a long period of time, and as a result, has extremely small wear and also has a shock absorbing function. Became .
- an artificial joint using such an artificial joint member, a patient can live a daily life as long as a healthy person for a long period of time.
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2003211465A AU2003211465A1 (en) | 2002-02-19 | 2003-02-19 | Artificial joint member made of polymeric material |
DE60334767T DE60334767D1 (de) | 2002-02-19 | 2003-02-19 | Künstliches gelenkglied aus einem polymeren material |
AT03705299T ATE486619T1 (de) | 2002-02-19 | 2003-02-19 | Künstliches gelenkglied aus einem polymeren material |
EP03705299A EP1433488B1 (en) | 2002-02-19 | 2003-02-19 | Artificial joint member made of polymeric material |
US10/489,112 US7785372B2 (en) | 2002-02-19 | 2003-02-19 | Artificial joint member with grafted polymer surface |
HK05103709.1A HK1070301A1 (en) | 2002-02-19 | 2005-05-03 | Artificial joint member made of polymeric material |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002042272 | 2002-02-19 | ||
JP2002-42272 | 2002-02-19 |
Publications (1)
Publication Number | Publication Date |
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WO2003070289A1 true WO2003070289A1 (fr) | 2003-08-28 |
Family
ID=27750491
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2003/001750 WO2003070289A1 (fr) | 2002-02-19 | 2003-02-19 | Element d'articulation artificielle realise en materiau polymere |
Country Status (8)
Country | Link |
---|---|
US (1) | US7785372B2 (ja) |
EP (1) | EP1433488B1 (ja) |
CN (1) | CN100566762C (ja) |
AT (1) | ATE486619T1 (ja) |
AU (1) | AU2003211465A1 (ja) |
DE (1) | DE60334767D1 (ja) |
HK (1) | HK1070301A1 (ja) |
WO (1) | WO2003070289A1 (ja) |
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JP2008148850A (ja) * | 2006-12-15 | 2008-07-03 | Japan Medical Materials Corp | 低摩耗性摺動部材及びそれを用いた人工関節 |
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US9598544B2 (en) | 2005-08-25 | 2017-03-21 | University Of Washington Through Its Center For Commercialization | Particles coated with zwitterionic polymers comprising sulfobetaine or carboxybetaine |
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0722973A1 (en) * | 1995-01-20 | 1996-07-24 | The University Of Southern California | Chemically crosslinked ultrahigh molecular weight polyethylene for artificial human joints |
WO2001005855A1 (fr) * | 1999-07-14 | 2001-01-25 | Nof Corporation | Copolymere statistique, procede de production d'un tel copolymere et materiau medical associe |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6387379B1 (en) * | 1987-04-10 | 2002-05-14 | University Of Florida | Biofunctional surface modified ocular implants, surgical instruments, medical devices, prostheses, contact lenses and the like |
US4961954A (en) * | 1987-04-10 | 1990-10-09 | University Of Florida | Surface modified surgical instruments, devices, implants, contact lenses and the like |
EP0519087B1 (en) * | 1991-05-21 | 1997-04-23 | Hewlett-Packard GmbH | Method for pretreating the surface of a medical device |
JPH05220218A (ja) * | 1992-02-13 | 1993-08-31 | Norio Nakabayashi | 抗血栓性再生セルロース系膜及びその製造方法 |
JP3308010B2 (ja) * | 1992-12-15 | 2002-07-29 | ポーラ化成工業株式会社 | 被膜安定化リポソーム及びその製造方法 |
US6005160A (en) * | 1996-02-22 | 1999-12-21 | National Science Council | Heterobifunctional membrane in application of artificial cornea |
US6228900B1 (en) * | 1996-07-09 | 2001-05-08 | The Orthopaedic Hospital And University Of Southern California | Crosslinking of polyethylene for low wear using radiation and thermal treatments |
US6258371B1 (en) * | 1998-04-03 | 2001-07-10 | Medtronic Inc | Method for making biocompatible medical article |
JPH11318960A (ja) | 1998-05-12 | 1999-11-24 | Nissin Electric Co Ltd | 人工関節及びその製造方法 |
ATE337805T1 (de) * | 1999-07-28 | 2006-09-15 | Nof Corp | Medizinische materialien und verfahren zu deren herstellung |
-
2003
- 2003-02-19 EP EP03705299A patent/EP1433488B1/en not_active Expired - Lifetime
- 2003-02-19 CN CNB038010879A patent/CN100566762C/zh not_active Expired - Lifetime
- 2003-02-19 WO PCT/JP2003/001750 patent/WO2003070289A1/ja active Application Filing
- 2003-02-19 US US10/489,112 patent/US7785372B2/en active Active
- 2003-02-19 AT AT03705299T patent/ATE486619T1/de not_active IP Right Cessation
- 2003-02-19 AU AU2003211465A patent/AU2003211465A1/en not_active Abandoned
- 2003-02-19 DE DE60334767T patent/DE60334767D1/de not_active Expired - Lifetime
-
2005
- 2005-05-03 HK HK05103709.1A patent/HK1070301A1/xx not_active IP Right Cessation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0722973A1 (en) * | 1995-01-20 | 1996-07-24 | The University Of Southern California | Chemically crosslinked ultrahigh molecular weight polyethylene for artificial human joints |
WO2001005855A1 (fr) * | 1999-07-14 | 2001-01-25 | Nof Corporation | Copolymere statistique, procede de production d'un tel copolymere et materiau medical associe |
EP1211268A1 (en) | 1999-07-14 | 2002-06-05 | Nof Corporation | Random copolymer, process for the production thereof and medical material |
Non-Patent Citations (3)
Title |
---|
CLINICALORTHOPAEDICS AND RELATED RESEARCH, no. 333, 1996, pages 96 - 107 |
HIROKI FUKUI ET AL.: "Rin shishitsu polymer o hyomen ni koteika shita iryo-yo zairyo to sono kino", POLYMER PREPRINTS, vol. 48, no. 10, 1999, pages 2425 - 2426, XP002967688 * |
THE JOURNAL OF ARTHROPLASTY, vol. 14, no. 7, 1999, pages 781 - 787 |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9598544B2 (en) | 2005-08-25 | 2017-03-21 | University Of Washington Through Its Center For Commercialization | Particles coated with zwitterionic polymers comprising sulfobetaine or carboxybetaine |
JP2007202965A (ja) * | 2006-02-06 | 2007-08-16 | Japan Medical Materials Corp | 低摩耗性摺動部材及びそれを用いた人工関節 |
US9044323B2 (en) | 2006-02-06 | 2015-06-02 | Kyocera Medical Corporation | High wear-resistant bearing material and artificial joint replacement using the same |
JP2008148850A (ja) * | 2006-12-15 | 2008-07-03 | Japan Medical Materials Corp | 低摩耗性摺動部材及びそれを用いた人工関節 |
CN110251736A (zh) * | 2019-06-28 | 2019-09-20 | 南京理工大学 | 两性离子聚合物刷润滑剂及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
EP1433488B1 (en) | 2010-11-03 |
DE60334767D1 (de) | 2010-12-16 |
US20040243249A1 (en) | 2004-12-02 |
EP1433488A4 (en) | 2008-02-06 |
US7785372B2 (en) | 2010-08-31 |
HK1070301A1 (en) | 2005-06-17 |
AU2003211465A1 (en) | 2003-09-09 |
EP1433488A1 (en) | 2004-06-30 |
CN100566762C (zh) | 2009-12-09 |
ATE486619T1 (de) | 2010-11-15 |
CN1556714A (zh) | 2004-12-22 |
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