JP5936566B2 - Manufacturing method of sliding member - Google Patents

Description

  The present invention relates to a medical material and a manufacturing method thereof, and more particularly, to a sliding member used for an artificial joint and a manufacturing method thereof.

  In recent years, with the aging of society, the number of patients requiring support and care has increased rapidly. About 20-30% of these patients have impaired functioning of motor organs (such as joints and spine, and nerves, muscles and ligaments to move the skeleton). In particular, loss of walking ability increases the risk of other diseases such as dementia and visceral diseases.

  If the ability to walk is lost due to hip trauma (such as fractures) or hip disorders (such as osteoarthritis and rheumatoid arthritis), one option is hip replacement. Artificial hip replacement is an operation in which a hip joint in which a functional disorder has occurred is replaced with an artificial joint. Hip replacement not only restores the ability of the patient to walk, but also relieves hip pain.

  The useful life of various artificial joints including artificial hip joints is generally said to be about 15 to 20 years. Accordingly, patients may have to undergo surgery (prosthesis replacement) 15-20 years after undergoing artificial joint replacement. In order to avoid prosthetic joint replacement as much as possible, prosthetic joints with a long service life are desired.

One reason why artificial joint revision is required is loosening of the artificial joint. For example, many hip prostheses use polyethylene (PE) liners and metallic or ceramic femoral heads. When the prosthesis is operated, the liner made of soft material is worn by the femoral head made of hard material, resulting in submicron sized PE wear powder. Macrophages promote the formation and activation of osteoclasts when macrophages engulf the abrasion powder generated in the body. As a result, osteolysis by osteoclasts occurs in the bone around the implant, resulting in loosening of the artificial joint. As described above, the loosening of the artificial joint is caused by a biological reaction to a foreign substance called “PE wear powder”.
Therefore, in order to suppress the loosening of the artificial joint, it is effective to “reduce the generation of PE abrasion powder (improve wear resistance)”.

  In order to improve wear resistance, it is known to use a liner made of crosslinked polyethylene (CLPE) (for example, Patent Document 1). CLPE can be obtained by irradiating normal PE with high energy rays (gamma rays, electron beams, etc.) to cause a crosslinking reaction. Since CLPE is superior to ordinary PE in wear resistance, generation of wear powder from the liner can be reduced.

However, when free radicals are generated in PE by irradiation with high energy rays, the molecular chain of PE may be cut by the free radicals, and the mechanical strength of the liner may be reduced. In addition, the liner placed in the body for a long period of time may cause PE molecular chains to be cut by oxidation, resulting in a decrease in the mechanical strength of the liner. Decreasing the mechanical strength of the liner is undesirable because it reduces the load bearing and wear resistance of the liner.
Therefore, in order to eliminate free radicals in PE and to increase the oxidation resistance of PE, a liner is manufactured using PE containing an antioxidant (for example, vitamin A, vitamin C and vitamin E). Attempts have been made (for example, Patent Document 2).

  As another attempt to improve the wear resistance, it is known to coat the surface of the liner with a highly lubricious polymer film (for example, Patent Documents 3 to 5). As the polymer film, a 2-methacryloyloxyethyl phosphorylcholine (MPC) film showing extremely high lubricity in a wet environment is used.

JP 2000-514482 A Japanese Patent No. 4256096 JP 2003-310649 A Japanese Patent No. 4963638 Japanese Patent No. 5028080

In order to further extend the service life of the artificial joint, it is required to achieve both the wear resistance and the oxidation resistance of the liner. For example, based on the contents disclosed in Patent Documents 2 and 3, “a liner provided with a base material made of an antioxidant-containing PE and a highly lubricious polymer film coated on the surface of the base material” If it can be manufactured, a liner capable of maintaining excellent wear resistance and oxidation resistance over a long period of time should be obtained by the synergistic effect of the antioxidant and the polymer film.
However, when the inventors manufactured such a liner, problems such as difficulty in forming a continuous polymer film, or easy peeling of the polymer film from the substrate occur, and are expected. Such wear resistance and oxidation resistance were not achieved at the same time.

  Then, an object of this invention is to provide the manufacturing method of the sliding member (liner) which has the outstanding abrasion resistance and oxidation resistance, and the sliding member obtained by the manufacturing method.

A method for producing a sliding material according to the present invention includes a step of forming a base material made of a polymer material containing a radical scavenger, a step of cleaning at least a part of the surface of the base material with a cleaning liquid, Forming a polymer film on at least a part of the surface by fixing a polymer chain having a phosphorylcholine group to at least a part of the surface after the washing by graft bonding. The step of forming includes irradiating at least a part of the surface with ultraviolet light having an intensity of 0.5 mW / cm ² or more in a state where the polymerizable monomer having the phosphorylcholine group is in contact.

  In the production method of the present invention, at least a part of the surface of the base material is washed with a cleaning liquid, and further, the ultraviolet intensity when forming a polymer film is appropriately controlled, thereby continuously (that is, without holes). The polymer film can be formed in close contact with the substrate. Thereby, the sliding member excellent in abrasion resistance can be obtained.

  According to the manufacturing method of the present invention, a sliding member having excellent wear resistance and oxidation resistance can be manufactured by including a step of cleaning with a cleaning liquid.

FIG. 1 is a schematic view of an artificial hip joint using the sliding member according to the first embodiment. FIG. 2 is a schematic perspective view of the sliding member according to the first embodiment. FIG. 3 is a graph showing the measurement results of the contact angle with respect to water for the samples 1f to 1i measured in Example 2. 4A to 4D are transmission electron microscope (TEM) images of samples 1a to 1d taken in Example 3. FIG. 5 shows the measurement results of samples 1a to 1f measured in Example 4. FIG. FIG. 5A is a graph showing the measurement result of the surface atomic concentration, and FIG. 5B is a graph showing the measurement result of the contact angle with respect to water. FIG. 6 is a graph showing the results of wear test 1 of samples 1d, 1j, and 1k performed in Example 5. FIG. 7 is a schematic view of a wear test apparatus used in the wear test 2 of Example 5. FIG. 8 is a graph showing the results of the abrasion test 2 of the samples 1d, 1j, and 1k performed in Example 5. 9A and 9B are graphs showing the results of oxidation experiments of samples 1d, 1j, and 1k performed in Example 6. FIG. FIG. 10 is a graph showing the measurement results of contact angles with respect to water for the samples 1m to 1r measured in Example 7. FIG. 11 is a graph showing the measurement results of the contact angle with respect to water for Samples 2a to 2h measured in Example 9. 12 is a graph showing the measurement results of the phosphoric acid index for samples 2a to 2h measured in Example 10. FIG. FIG. 13 is a graph showing the measurement results of film thickness for samples 2a to 2h measured in Example 11. 14A and 14B are TEM images of samples 2b and 2c measured in Example 12. FIG. FIGS. 15A and 15B are TEM images of samples 2e and 2f measured in Example 12. FIG. FIG. 16 is a graph showing the measurement results of the surface atom concentration for Samples 2a to 2h measured in Example 13. FIG. 17 is a graph showing the measurement results of the contact angle with respect to water for Samples 3a to 3i measured in Example 15. FIG. 18 is a graph showing the measurement results of the phosphoric acid index for Samples 3a to 3i measured in Example 16. FIG. 19 is a graph showing the film thickness measurement results for samples 3a to 3i measured in Example 17. 20A and 20B are TEM images of samples 3d and 3e measured in Example 18. FIG. FIG. 21 is a graph showing the measurement results of the surface atom concentration of Samples 3a to 3i measured in Example 19.

<Embodiment 1>
FIG. 1 is a schematic diagram of an artificial hip joint 1. The artificial hip joint 1 is composed of a sliding member (liner) 10 fixed to the acetabulum 94 of the hipbone 93 and a femoral stem 20 fixed to the proximal end of the femur 91. As shown in FIG. 1 and FIG. 2, the liner 10 is coated with a base material 12 having a substantially hemispherical mortar fixing surface 14 and a sliding surface 16 recessed in a substantially hemispherical shape, and the sliding surface 16. A polymer film 30 is provided. By fitting and sliding the head 22 of the femoral stem 20 on the covered sliding surface 16 (covered sliding surface 161), it functions as a hip joint.

  The substrate 12 of the liner 10 is formed from a polymer material containing a radical scavenger. As the polymer material, for example, a PE-based material can be used. The “radical scavenger” is a compound that captures and extinguishes radicals generated in the substrate 12. The radical scavenger also has the ability to inactivate substances (such as active oxygen) that cause oxidation.

  In the present invention, since a material containing a radical scavenger is used for the base material 12 of the liner 10, even if free radicals are generated in the base material 12 during the production process of the liner 10, the free radicals are still a radical scavenger. Is extinguished by. Therefore, it can suppress that the polymeric material which comprises the base material 12 deteriorates with a free radical. Moreover, since the base material 12 containing a radical scavenger can inactivate active oxygen etc., it can suppress that the base material 12 oxidatively degrades by active oxygen etc. in the living body.

  The polymer film 30 coated on the surface of the sliding surface 16 is made of a polymer having a phosphorylcholine group. Specifically, the polymer film 30 has a structure in which polymer chains having phosphorylcholine groups are arranged on the surface. Such a structure is similar to the structure of a biological membrane.

  A biological membrane constituting a cartilage surface such as a living joint part is an aggregate of phospholipid molecules, and the surface is microscopically covered with a phosphorylcholine group (Ishihara: Surgery Vol. 61, p. 132 (1999)). Biological articular cartilage constitutes a lubricated joint surface with a very low coefficient of friction by holding a lubricating liquid inside the agglomerate of hydrophilic polymer composed of the biological membrane, proteoglycan and hyaluronic acid. The polymer film 30 of the present invention also has a high affinity with the lubricating liquid as in the case of the living articular cartilage, and can retain the lubricating liquid inside the film, so that it can be compared with the sliding surface 16 of the conventional liner 10. The friction coefficient can be lowered.

  By covering the sliding surface 16 of the PE substrate 12 with a polymer film, the contact angle with water is from about 90 ° (contact angle of PE) to about 14 ° (contact angle of the polymer film 30). Can be reduced. Further, when the continuity of the polymer film 30 decreases, the contact angle increases. For example, when the polymer film 30 having a contact angle with water of 40 ° or less is provided on the sliding surface 16 of the liner 10, the wear resistance of the liner 10 can be significantly improved. This is presumably because the polymer film 30 having a contact angle of 40 ° or less does not have a hole having a size that reduces the wear resistance, and therefore local wear can be suppressed.

  Thus, since the sliding surface 16 is covered with the polymer film 30 having a contact angle with respect to water of 40 ° or less, local abrasion is less likely to occur on the sliding surface 16 of the base material 12, so that the wear resistance is excellent. A liner 10 can be obtained. Therefore, the service life of the artificial joint can be extended by using such a liner 10. In particular, it is more preferable to cover the sliding surface 16 with the polymer film 30 having a contact angle with water of 35 ° or less because the continuity of the polymer film 30 is further increased and the service life is further increased. Furthermore, it is more preferable that the sliding surface 16 is covered with the polymer film 30 having a contact angle with water of 15 ° or less because the continuity of the polymer film 30 is further increased and the service life is remarkably increased.

The smaller the number of holes in the polymer film 30, the higher the density of the polymer film 30. Therefore, the higher the density of the polymer film 30 of the liner 10, the higher the wear resistance of the liner 10. As an index for knowing the density of the polymer chain, atomic concentrations of phosphorus atoms and nitrogen atoms can be used.
One monomer molecule having a phosphorylcholine group contains one phosphorus atom and one nitrogen atom. Therefore, the phosphorus atom and nitrogen atom content (corresponding to the atomic concentration) contained in the measurement region is proportional to the number of monomers in the range. That is, the atomic concentration of phosphorus atoms and nitrogen atoms can be an index for knowing the density of the polymer film 30.

  X-ray photoelectron spectroscopy (XPS) analysis can be used to determine the atomic concentration of phosphorus atoms and nitrogen atoms. Since XPS has an extremely small analysis area, XPS has an advantage that it can be measured even if the sample surface has a concavo-convex shape. The polymer film 30 having a phosphorus atom concentration of 2.9 atom% or more and a nitrogen atom concentration of 3.1 atom% or more obtained from XPS analysis is considered to be a polymer film 30 having a high density.

  The phosphorus atom concentration and the nitrogen atom concentration are excellent as an index for knowing the density of the polymer film 30, but may not reflect the presence or absence of holes when the polymer film 30 is macroscopically observed. This is because, since the XPS analysis region is extremely small, there may be a situation in which no hole exists in the measurement range even if the polymer film 30 has a hole when viewed macroscopically. Therefore, the evaluation of the polymer film 30 is not based on the result of the atomic concentration alone, but is determined in combination with the result of the macroscopic physical property measurement of the polymer film 30 (for example, the contact angle with water). Is desirable.

  When the polymer chain constituting the polymer film 30 becomes longer (that is, when the film thickness of the polymer film 30 becomes thicker), the continuity of the polymer film 30 improves. This is because when the film thickness of the polymer film 30 is thin, a portion recognized as a “hole” of the polymer film 30 is covered by an increase in the polymer chain around the hole. However, the polymer chain covering the portion recognized as the hole is not bonded to the sliding surface 16 of the base material 12 exposed from the hole of the polymer film 30. Therefore, when the polymer film 30 is viewed in cross section, a gap is formed between the sliding surface 16 of the substrate 12 and the polymer film 30.

  The polymer film 30 in which a gap exists between the sliding surface 16 of the substrate 12 has a low binding force to the sliding surface 16. Therefore, the peel strength of the polymer film 30 tends to decrease. In other words, the polymer film 30 that does not substantially have a gap between the base material 12 and the sliding surface 16 has a high binding force to the sliding surface 16. Therefore, when the liner 10 provided with the polymer film 30 having substantially no gap is used as an artificial joint, the possibility that the polymer film 30 is peeled off from the base material 12 is reduced, and the useful life of the artificial joint is increased. can do.

Next, a method for manufacturing the sliding member (liner 10) according to the present invention will be described.
The manufacturing method of the liner 10 is as follows:
1. Forming the substrate 12;
2. Cleaning a part of the substrate surface (sliding surface 16);
3. Forming a polymer film 30 on the sliding surface 16.

(1. Process of forming substrate 12)
In this step, the base material 12 made of a polymer material containing a radical scavenger is formed. As the forming means, a processing method of cutting a block-shaped polymer material into a shape of the base material 12 can be used. The block-shaped polymer material can be produced, for example, by mixing a polymer material powder (for example, PE powder) and a radical scavenger (liquid or powder), and compression-molding the obtained mixed powder. it can.
In addition, the shaping | molding method (what is called a near net shape shaping | molding method) which compression-molds mixed powder to the shape of the base material 12 can also be used. Since the base material 12 molded by the near net shape molding method does not need to be cut or only needs to be cut slightly, the cost and labor required for the cutting can be reduced.

  In order to increase the abrasion resistance of the base material 12, the polymer material constituting the base material 12 may be subjected to a crosslinking treatment. For example, a block-shaped polymer material (for example, PE) before molding is irradiated with high energy rays (for example, X-rays, gamma rays or electron beams) to produce a block-shaped crosslinked polymer material (for example, CLPE), The obtained crosslinked polymer material can be cut to obtain the substrate 12. In another example, first, a base material 12 made of a polymer material (for example, PE) may be prepared, and the base material 12 may be irradiated with a high energy ray for crosslinking.

  In the case of a polymer material containing a radical scavenger as in the present invention, some of the generated radicals are trapped by the radical scavenger. Therefore, in order to advance a sufficient crosslinking reaction in the polymer material containing the radical scavenger, it is necessary to irradiate high energy rays at a high dose (for example, 75 kGy to 200 kGy). In addition, in PE which does not contain a radical scavenger, sufficient crosslinking reaction can be advanced by irradiating 50-100 kGy of high energy rays.

  Thus, the crosslinking treatment can be performed before or after the molding process. However, the crosslinking treatment is desirably performed before the molding process for the following reason. Since high energy beam irradiation necessary for the crosslinking treatment may change the dimensions of the substrate 12, it is not desirable to perform the crosslinking treatment after the molding process. Moreover, it is desirable that the crosslinking treatment be performed before “2. The step of cleaning the sliding surface 16” for the following reason.

  In the present invention, “3. Step of forming polymer film” is performed after “2. Step of cleaning sliding surface 16”. Since the cleaning effect of the sliding surface 16 decreases with time, it is not desirable to perform another process (for example, a crosslinking process) between these processes. Further, since high energy beam irradiation necessary for the crosslinking treatment is not preferable for the polymer film 30, it is not desirable to perform the crosslinking treatment after “3. Step of forming a polymer film”. For these reasons, the crosslinking treatment is preferably performed before the washing step.

  The crosslinking treatment of the polymer material can also be performed by adding a crosslinking agent to the polymer material. However, since the liner 10 used for the artificial joint is installed in the living body for a long period of time, a crosslinking agent with uncertain biological safety cannot be used.

(2. Step of cleaning the sliding surface 16)
In this step, at least a part of the surface of the substrate 12 (specifically, the sliding surface 16) is cleaned with a cleaning liquid. By this process, the polymer film 30 with few defects can be formed in the following “3. Process of forming the polymer film 30”.
In order to form the polymer film 30, the polymer chains constituting the polymer film 30 are grafted to the sliding surface 16 of the substrate 12. However, when a radical scavenger is present on the sliding surface 16 of the base material 12, the polymer chain tends to be difficult to graft onto the sliding surface 16. This is because the radical scavenger is interposed between the monomer that forms the polymer film 30 and the sliding surface 16, and the monomer cannot approach the sliding surface 16, and as a result, the neighboring region has a polymer chain. This is thought to be because of the inability to graft. The polymer chains constituting the polymer film 30 are formed by a surface initiated graft polymerization reaction using radicals generated on the surface of the sliding surface 16. However, it is considered that one of the causes is that the radical scavenger contained in the polymer material inhibits the surface-initiated graft polymerization reaction by capturing and extinguishing the radicals necessary for this radical polymerization. Therefore, in the region near the sliding surface 16, a hole is generated in the polymer film 30 and / or a gap is generated between the polymer film 30 and the sliding surface 16.

  Therefore, by washing the sliding surface 16 before forming the polymer film 30 and removing the radical scavenger only from the sliding surface 16, the monomer that forms the polymer film 30 can be used on the entire sliding surface 16. Can be approached over. As a result, it is possible to form the polymer film 30 having no defects such as holes and gaps or few defects.

  As described above, the purpose of cleaning is to clean the radical scavenger on the sliding surface 16. Therefore, the cleaning liquid to be used preferably has a high cleaning effect of the radical scavenger. On the other hand, if an organic solvent capable of dissolving the polymer material constituting the substrate 12 is used as the cleaning liquid, there is a risk of damaging the surface of the sliding surface 16, which is not preferable. Moreover, since the density | concentration of the radical scavenger contained in the inside of a polymeric material may also be reduced and the antioxidant ability of the liner 10 may be reduced, it is not preferable. Therefore, it is preferable to use an aqueous solution containing a surfactant as the cleaning liquid. The lipophilic radical scavenger can be removed by the cleaning effect of the surfactant, and the hydrophilic radical scavenger can be removed by water as a solvent. Further, the aqueous solution containing the surfactant has an advantage that the possibility of damaging the base material 12 made of an organic material is extremely low.

  In the washing step, washing can be performed at a washing temperature of 40 to 80 ° C., more preferably 70 to 80 ° C., a washing time of 6 to 48 hours, and more preferably 12 to 48 hours. If the polymer film 30 is cleaned under these conditions, the polymer film 30 having extremely few defects such as holes and gaps can be formed when the polymer film 30 is formed in the next step. For example, when cleaning is performed at a cleaning temperature of 70 ° C. and a cleaning time of 6 hours, the polymer film 30 with few defects can be formed. When the cleaning temperature is lower than 70 ° C., the same effect can be obtained by making the cleaning time longer than 6 hours. When the cleaning temperature is higher than 70 ° C., the same effect can be obtained even if the cleaning time is shorter than 6 hours.

(3. Process of forming polymer film 30)
In this step, a polymer chain having a phosphorylcholine group is fixed to at least a part of the surface of the substrate 12 after washing (specifically, the sliding surface 16) by graft bonding, thereby increasing the height on the sliding surface 16. A molecular film 30 is formed.
In order to manufacture the liner 10 according to the present invention, it is necessary to fix the polymer film 30 to the sliding surface 16 of the liner 10. Several fixing methods have been conventionally known. In the present invention, a polymer is obtained by bonding a polymerizable monomer having a phosphorylcholine group to the sliding surface 16 by a graft polymerization reaction started from the surface of the sliding surface 16. The membrane 30 is fixed. In this method, only the sliding surface 16 can be modified without deteriorating the performance such as the strength of the polymer material constituting the liner 10, the bonding portion is chemically stable, and a large amount of phosphorylcholine groups can be obtained. Is formed on the sliding surface of the artificial joint member to increase the density of the polymer film 30.

A specific procedure for forming the polymer film 30 includes irradiating the sliding surface 16 with ultraviolet light having an intensity of 0.5 mW / cm ² or more in a state where the polymerizable monomer having a phosphorylcholine group is in contact. When the ultraviolet intensity is 0.5 mW / cm ² or more, the polymer film 30 can be formed on the sliding surface 16. To form the small polymer film 30 having more defects, the irradiation intensity of ultraviolet light is preferably less than 3.5 mW / cm ² or more 10.0 mW / cm ^2, in particular, 3.5 mW / cm ² or more and 7. More preferably, it is 5 mW / cm ² or less.

  The irradiation time of the ultraviolet rays is preferably 45 minutes or longer, and the continuous polymer film 30 can be formed on the sliding surface 16. It is more preferable that the ultraviolet irradiation time be 90 minutes or longer because the polymer film 30 to be formed becomes thick. Although there is no preferable upper limit of the irradiation time from the viewpoint of the characteristics of the polymer film 30 to be formed, the irradiation time is preferably 180 minutes or less from the viewpoint of manufacturing efficiency.

The ultraviolet irradiating when converted to total energy (= intensity (mW / cm ²⁾ × Time (sec)) is preferably from greater than 54000mJ / cm ² than 6900mJ / cm ^2, continuously sliding surface 16 The polymer film 30 can be formed. In order to form the polymer film 30 with fewer defects, the total energy is preferably 8100 mJ / cm ² or more and 40500 mJ / cm ² or less.

In order to bring the polymerizable monomer having a phosphorylcholine group into contact with the sliding surface 16, for example, the sliding surface 16 of the liner 10 may be immersed in a solution containing the polymerizable monomer. Further, a photopolymerization initiator may be applied to the sliding surface 16 of the substrate 12.
The photopolymerization initiator is a compound that generates radicals by irradiating light having a wavelength necessary for excitation (for example, ultraviolet light or the like) with an intensity necessary for excitation. When the photopolymerization initiator applied to the sliding surface 16 is irradiated with ultraviolet rays or the like, first, radicals are generated in the photopolymerization initiator. Subsequently, the generated radicals move to the sliding surface 16, and the radicals on the surface of the moved sliding surface 16 react with the polymerizable monomer in the solution to start graft polymerization. Polymerizable monomers in the solution are successively polymerized to form a polymer chain. A polymer film 30 is composed of an assembly of polymer chains covering the sliding surface 16.

  The density of the resulting polymer film 30 can vary depending on the concentration of the solution containing the polymerizable monomer, the temperature of the solution, the intensity of the ultraviolet light, and the irradiation time.

  Below, the material suitable for the sliding member of this invention and its manufacturing method is explained in full detail.

(Substrate 12)
The substrate 12 of the liner 10 is molded from a material containing a radical scavenger into a polymer material. As the polymer material, for example, PE-based material can be used, and it is particularly preferable to use ultrahigh molecular weight polyethylene (UHMWPE). UHMWPE is suitable for the substrate 12 because it is excellent in mechanical properties such as wear resistance and deformation resistance among PE-based materials. UHMWPE has higher wear resistance as the molecular weight increases. Therefore, the molecular weight is at least 100 × 10 ⁴ g / mol (1 million g / mol) or more, preferably 300 × 10 ⁴ g / mol (3 million g / mol). It is preferable to use the above UHMWPE.

(Radical scavenger)
As the radical scavenger, a radical scavenger having a phenolic hydroxyl group or a tocotrienol group is preferable. In particular, a radical scavenger having a tocotrienol group is more preferable because it has a higher antioxidant capacity than a radical scavenger having a tocophenol group.

  Specific examples of the radical scavenger include hindered amine radical scavengers, hindered phenol radical scavengers, phosphorus radical scavengers, sulfur radical scavengers, and the like.

  Examples of the hindered amine radical scavenger include 1,2,2,6,6, -pentamethylpiperidinyl methacrylate, 2,2,6,6, -tetramethylpiperidinyl methacrylate, bis (2,2, 6,6-tetramethyl-4-piperidine) sebacate, dimethyl succinate and 4-hydroxy-2,2,6,6-tetramethyl-1-piperidineethanol, N, N ′, N ″, N '' '-Tetrakis- (4,6-bis- (butyl- (N-methyl-2,2,6,6-tetramethylpiperidin-4-yl) amino) -triazin-2-yl) -4,7 -Diazadecane-1,10-diamine, decanedioic acid bis (2,2,6,6-tetramethyl-1- (octyloxy) -4-piperidinyl) ester, bis (1,2,2,6,6- pen Methyl-4-piperidyl) [[3,5-bis (1,1-dimethylethyl) -4-hydroxyphenyl] methyl] butyl malonate, cyclohexane and N-butyl-2,2,6,6-tetraperoxide Reaction product of methyl-4-piperidinamine-2,4,6-trichloro-1,3,5-triazine with 2-aminoethanol, bis (1,2,2,6,6- Pentamethyl-4-piperidyl) sebacate, methyl-1,2,2,6,6-pentamethyl-4-piperidyl sebacate, tetrakis (1,2,2,6,6-pentamethyl-4-piperidine) -1,2 3,4-butanetetracarboxylate and the like.

  Examples of the hindered phenol radical scavenger include 2-t-butyl-4-methoxyphenol, 3-t-butyl-4-methoxyphenol, 2,6-di-t-butyl-4-ethylphenol, 2 , 2′-methylene-bis (4-methyl-6-tert-butylphenol), 4,4′-thiobis- (3-methyl-6-tert-butylphenol), 4,4′-butylidenebis (3-methyl-6) -T-butylphenol), 1,1,3-tris (2-methyl-4-hydroxy-5-t-butylphenyl) butane, 1,3,5-trimethyl-2,4,6-tris (3,5 -Di-t-butyl-4-hydroxybenzyl) benzene and tetrakis- [methylene-3- (3 ', 5'-di-t-butyl-4'-hydroxyphenyl) propionate] methane etc. And the like.

  Examples of the phosphorus radical scavenger include triphenyl phosphite, diphenylisodecyl phosphite, phenyl diisodecyl phosphite, 4,4′-butylidene-bis (3-methyl-6-t-butylphenylditridecyl) phosphite, Cyclic neopentanetetrayl bis (nonylphenyl) phosphite, cyclic neopentanetetrayl bis (dinonylphenyl) phosphite, cyclic neopentanetetrayl tris (nonylphenyl) phosphite, cyclic neopentanetetrayl tris (Dinonylphenyl) phosphite, 10- (2,5-dihydroxyphenyl) -10H-9-oxa-10-phosphaphenanthrene-10-oxide, diisodecylpentaerythritol diphosphite and Scan (2,4-di -t- butyl-phenyl) phosphite.

  Examples of the sulfur-based radical scavenger include dilauryl 3,3′-thiodipropionate, distearyl 3,3′-thiodipropionate, N-cyclohexylthiophthalimide, Nn-butylbenzenesulfonamide, and the like. .

Moreover, as a radical scavenger, fat-soluble vitamin Es (tocopherols) can also be used.
Examples of the fat-soluble vitamin E include tocopherol and tocotrienol, and derivatives thereof, such as dl-α-tocopherol, dl-β-tocopherol, dl-γ-tocopherol, dl-δ-tocopherol, and dl-α-tocopherol acetate. Nicotinic acid-dl-α-tocopherol, linoleic acid-dl-α-tocopherol, tocopherol and its derivatives such as dl-α-tocopherol succinate, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol, etc. Can be mentioned. These may be used singly or in combination, but are preferably used in the form of a mixture, and those in the form of a mixture include those called extracted tocopherol, mixed tocopherol and the like.

  Among these radical scavengers, vitamin E and hindered amine compounds are preferable. Vitamin E and hindered amine compounds are suitable for use in the substrate 12 used in vivo because their biosafety has been confirmed.

  The content of the radical scavenger is preferably from 0.01 to 5% by weight, more preferably from 0.05 to 0.7% by weight, based on the polymer material constituting the substrate 12, from the viewpoint of the antioxidant effect. 0.05 to 0.15% by weight is particularly preferred.

(Polymer film 30)
For the formation of the polymer film 30, a polymerizable monomer having a phosphorylcholine group is used. In particular, a monomer having a phosphorylcholine group at one end and a functional group capable of graft polymerization with the polymer material constituting the liner 10 at the other end is used. By selecting, the polymer film 30 can be grafted to the sliding surface 16 of the liner 10.
Suitable polymerizable monomers for the present invention include, for example, 2-methacryloyloxyethyl phosphorylcholine, 2-acryloyloxyethyl phosphorylcholine, 4-methacryloyloxybutylphosphorylcholine, 6-methacryloyloxyhexylphosphorylcholine, ω-methacryloyloxyethylene phosphorylcholine, 4- And styryloxybutyl phosphorylcholine. In particular, 2-methacryloyloxyethyl phosphorylcholine (MPC) is preferable.

  The MPC monomer has a chemical structural formula as shown below, and includes a phosphorylcholine group and a polymerizable methacrylic acid unit. The MPC monomer is characterized in that it can easily form a high molecular weight MPC polymer by radical polymerization (Ishihara et al .: Polymer Journal, Vol. 22, 355 (1990)). Therefore, when the polymer film 30 is synthesized from the MPC monomer, the graft bonding between the polymer film 30 and the sliding surface 16 can be performed under relatively mild conditions, and the polymer film 30 having a high density is formed. A large amount of phosphorylcholine groups can be formed on the sliding surface 16.

  The polymer film 30 that can be used in the present invention is not only a homopolymer composed of a single polymerizable monomer having a phosphorylcholine group, but also a copolymer composed of a monomer having a phosphorylcholine group and, for example, another vinyl compound monomer. It can also be formed from a polymer. Thereby, functions such as improvement of mechanical strength can be added to the polymer film 30.

(Surfactant)
The cleaning liquid used in the production method of the present invention may contain an organic solvent or water. In particular, the cleaning liquid is preferably one in which a surfactant is dissolved in water.
Examples of the surfactant are a nonionic surfactant, a cationic surfactant, an anionic surfactant, and an amphoteric surfactant. In particular, nonionic surfactants are preferred.

Nonionic surfactants and polyoxyethylene surfactants having an HLB value of 10 to 18 (particularly an HLB value of 13 to 18) are preferred. Examples of the polyoxyethylene surfactant include polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester (Tween 20 (registered trademark)), polyoxyethylene p-t-octylphenyl ether, polyoxyethylene p-t-nonylphenyl. Ether or the like can be used.
A nonionic surfactant can be used individually or in mixture of 2 or more types. The concentration of the nonionic surfactant is preferably 0.01 to 10.0% by weight, more preferably 0.1 to 5.0% by weight, still more preferably 0.1 to 1.0% by weight, particularly preferably. Is 0.3 to 1.0% by weight.

In order to examine the physical properties of the sliding member (liner 10) of the present application, samples 1a to 1j of the hip joint liner 10 as shown in FIG. 2 were prepared. The common manufacturing conditions for each sample are as follows.
[Step 1] A mixed powder was prepared by mixing UHMWPE powder and vitamin E liquid. The content of vitamin E was 0.1% by weight with respect to UHMWPE. The mixed powder was compression molded with a mold to form a base material 12 made of UHMWPE containing vitamin E. The obtained compression-molded body was irradiated with 100 kGy of gamma rays to cause a crosslinking reaction of PE, thereby obtaining a substrate 12 made of CLPE containing vitamin E.
[Step 2] The substrate 12 was immersed in a cleaning solution and cleaned for a predetermined time with stirring. The washing temperature was 70 ° C.
[Step 3] After washing, the substrate 12 was immersed in an acetone solution (concentration 10 mg / mL) of benzophenone (photopolymerization initiator) for 30 seconds, and then immediately pulled up to remove the solvent on the surface of the substrate 12. In a state where the substrate 12 is immersed in an MPC aqueous solution (concentration 0.5 mol / L, aqueous solution temperature 60 ° C.), ultraviolet light (wavelength 300 to 400 nm) having an intensity of 5.0 mW / cm ² on the sliding surface 16 of the substrate 12. Was irradiated for 90 minutes to form a polymer film (MPC polymer film) 30 grafted to the surface of the sliding surface 16.

In the above steps 1 to 3, the conditions that differ for each sample are described below.
(Sample 1a) A sample was prepared without washing in step 2.
(Sample 1b) In step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning solution, and cleaning was performed at a cleaning temperature of 70 ° C. and a cleaning time of 3 hours.
(Sample 1c) In step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning solution, and cleaning was performed at a cleaning temperature of 70 ° C. and a cleaning time of 6 hours.
(Sample 1d) In Step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning liquid, and cleaning was performed at a cleaning temperature of 70 ° C. and a cleaning time of 12 hours.
(Sample 1e) In Step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning solution, and cleaning was performed at a cleaning temperature of 70 ° C. and a cleaning time of 24 hours.
(Sample 1f) In step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning solution, and cleaning was performed at a cleaning temperature of 70 ° C. and a cleaning time of 48 hours.
(Sample 1g) In step 2, ethanol was used as a cleaning solution, and ultrasonic cleaning was performed with a cleaning time of 30 minutes.
(Sample 1h) In step 2, ethanol was used as a cleaning solution, and Soxhlet cleaning was performed with a cleaning time of 72 hours.
(Sample 1i) In step 2, acetone was used as a cleaning liquid, and ultrasonic cleaning was performed with a cleaning time of 30 minutes.
(Sample 1j) In step 1, the base material 12 was formed without adding vitamin E, and the dose of gamma rays was 50 kGy. Further, Step 2 was not performed.
(Sample 1k) In step 1, the base material 12 was formed without adding vitamin E, and the dose of gamma rays was 50 kGy. Also, steps 2 and 3 were not performed. That is, the sample was prepared without coating the polymer film 30 on the CLPE substrate 12.

In addition, the meaning of the abbreviation in this specification is as follows.
CLPE: Crosslinked polyethylene PMPC: MPC polymer film HD-CLPE: High molecular weight polyethylene crosslinked with high dose CLPE + E: Crosslinked polyethylene containing vitamin E

(Measurement of hydrophilicity (contact angle with water))
The contact angle (static contact angle) with respect to water was examined for the polymer films 30 provided on the samples 1f, 1g, 1h, and 1i. The measurement was performed by a droplet method using a surface contact angle measuring device DM300 manufactured by Kyowa Interface Science Co., Ltd. The measurement of the static surface contact angle by the droplet method was performed at 60 seconds after dropping pure water having a droplet volume of 1 μL on the sample surface in accordance with the ISO 15989 standard. The measurement result of the contact angle is shown in FIG.
Samples 1g and 1h washed with ethanol had a contact angle exceeding 40 °. Sample 1i washed with acetone had a contact angle of 40 ° or less. Sample 1f using non-ionic surfactant aqueous solution Tween 20 showed the lowest contact angle of about 30 °. The contact angle of the polymer film 30 being 40 ° or less suggests that the polymer film 30 has few defects. Therefore, it can be seen that the polymer film 30 with few defects can be formed on the samples 1f and 1i.
From this, it was found that a nonionic surfactant aqueous solution such as Tween 20 is advantageous for removing vitamin E from the sliding surface 16 of the substrate 12. Acetone also has a high ability to remove vitamin E, but if it is washed for 30 minutes, it may erode the PE of the base material 12 and roughen the sliding surface 16. It is not suitable as a moving member.

(Electron microscope observation)
The cross sections of Samples 1a to 1d were observed with TEM. Each sample was embedded in an epoxy resin and stained with ruthenium tetrachloride, and then an ultrathin section was cut out using an ultramicrotome to obtain a sample piece. The sample piece was observed at an acceleration voltage of 100 kV using a TEM (JEM-1010 type manufactured by JEOL Ltd.). A TEM image of each sample is shown in FIG.
In the sample 1 a (FIG. 4A) that was not washed, a gap 40 was confirmed between the sliding surface 16 of the substrate 12 and the polymer film 30. In the sample 1b (FIG. 4B) having a cleaning time of 3 hours, the continuous polymer film 30 was not formed, and the uncoated region UC (the hole of the polymer film 30) remained. The sample 1c (FIG. 4C) having a cleaning time of 6 hours and the sample 1d (FIG. 4D) having a cleaning time of 12 hours were formed with a polymer film 30 having no defect.
From this, it was found that when a nonionic surfactant is used as the cleaning liquid, the polymer film 30 with few defects can be formed by cleaning for 6 hours or more.

(X-ray photoelectron spectroscopy / hydrophilicity)
For samples 1a to 1f, the relationship between the cleaning time and the atomic concentration (atomic%) of phosphorus atoms and nitrogen atoms on the sliding surface 16 was examined. The atomic concentrations of phosphorus atoms and nitrogen atoms were measured using XPS analysis. Since XPS has a very small analysis area, the measurement result may reflect only local information. Therefore, a plurality of locations (9 locations in this example) for one sample were analyzed by XPS, and the average of the results was used as the atomic concentration of each sample.
For XPS analysis, Mg-Kα ray was used as an X-ray source, and measurement was performed under conditions of an applied voltage of 15 kV and a detection angle of 90 °. Using the obtained XPS spectrum, the atomic concentration of phosphorus atoms and the atomic concentration of nitrogen atoms were determined. The unit of atomic concentration is expressed as atom%.
The result of XPS analysis is shown in FIG. 5A. Moreover, the “contact angle with respect to water” for the same samples 1a to 1f is shown in FIG. 5B.

  In the sample 1a that was not washed, the phosphorus atom concentration of the polymer film 30 was 4.0 atom%, and the nitrogen atom concentration was 4.0 atom%. In Sample 1b with a cleaning time of 3 hours, the phosphorus atom concentration of the polymer film 30 was 4.8 atom%, and the nitrogen atom concentration was 4.2 atom%. For the sample 1c having a cleaning time of 6 hours, the sample 1d having a cleaning time of 12 hours, the sample 1e having a cleaning time of 24 hours, and the sample 1f having a cleaning time of 48 hours, the phosphorus atom concentration is 5.0 to 5.2 atom%, The concentration was 5.0 to 5.2 atom%.

  As shown in FIG. 5B, the contact angle with respect to water is 48 ° for sample 1a and 51 ° for sample 1b, both of which are greater than 40 °. On the other hand, in the samples 1c to 1f, the angle is 30 ° to 35 ° and 40 ° or less.

  When judging comprehensively from the TEM image in FIG. 4, the atomic concentration in FIG. 5A, and the contact angle with respect to water in FIG. 5B, the polymer film 30 with a contact angle with respect to water of 40 ° or less is a void 40 or an uncoated region UC It was found that the polymer film 30 had few defects.

(Abrasion test 1)
A wear test (pin-on-disk test) was performed using the sample pieces prepared under the conditions of Samples 1d, 1j, and 1k. The specimen used in the wear test was a 3 mm thick flat specimen, and the manufacturing method of each specimen was as described in the above-mentioned specimens 1d, 1j and 1k.
With reference to the ASTM F732 standard, a pin-on-disk type wear test apparatus (AMTI Ortho-POD) was used to conduct a multi-directional sliding test (test assuming frictional motion that occurs during normal walking in the hip joint). Cobalt chromium (Co-Cr) alloy was used for the pin type test piece. The multi-directional sliding test was performed in bovine serum at 37 ° C. The maximum load is 213N, and the test is performed up to 1 million times (1 × 10 ⁶ times) under the conditions of a sliding distance of 30 mm and a sliding speed of 1 Hz. It was evaluated with. The result is shown in FIG.

(Abrasion test 2)
A wear test was performed in an environment in which the sample (hip liner) prepared under the conditions of Samples 1d, 1j, and 1k and the artificial bone head were artificially slid to reproduce the usage state in the human body. The manufacturing method of each sample was as the above-mentioned samples 1d, 1j, and 1k.
In the wear test, a wear test apparatus (manufactured by MTS) that can simulate the state in which the hip joint slides while rotating and swinging was used. FIG. 7 is a schematic side view of the wear test apparatus 100, and a container 102 for storing a body fluid-like liquid is fixed to the rotary motor 106 in an inclined state (for example, 45 °). A holder 104 for fixing the hip joint liner 10 is disposed above the container 102. Inside the container 102, a head fixing shaft 108 having a head fixed to the tip is disposed, and a load F is applied to the head 22 in an upward direction with the head 22 fitted to the sliding surface 16 of the hip joint liner 10. Can be loaded.

In the wear test, in order to evaluate the wear resistance of the hip joint liner 10 in a state simulating the living body, during the test, the hip joint liner 10 and the bone head 22 were subjected to 0.1% sodium azide and 20 mM ethylenediamine. It was immersed in 25% bovine serum 110 containing trisodium tetraacetate. The bone head 22 was made of a commercially available Co—Cr alloy with a diameter of 26 mm, and the walking state was simulated by a double peak pawl walking condition having two peaks of 183 kgf and 280 kgf in one walking cycle per second. The test was conducted up to 10 million times (10 × 10 ⁷ times), and the amount of wear of the hip joint liner with each material over time was evaluated by its weight change. The result is shown in FIG.
In the graph of FIG. 8, the amount of wear may be negative. This is because the polymer film 30 of the hip joint liner and the base material 12 absorbed moisture, and thus the weight increased. In this embodiment, when the wear amount becomes negative (that is, when the weight increases), it is assumed that the wear amount is zero.

The results of wear tests 1 and 2 are examined in FIG.
It is considered that the replacement time of the sliding member (liner 10) is 1 mg of wear. In addition, 1.0 × 10 ⁶ times is estimated to be about one year.
Sample 1k formed from CLPE containing no vitamin E reached an abrasion amount of 1 mg after about 0.2 × 10 ⁶ times. That is, in the artificial joint using the liner 10 manufactured under the condition of the sample 1k, there is a possibility that re-replacement may be required relatively early.
The sample 1j formed of CLPE not containing vitamin E and provided with the polymer film 30 reached the wear amount of 1 mg after about 0.7 × 10 ⁶ times. That is, even in an artificial joint using the liner 10 manufactured under the conditions of the sample 1j, it may be necessary to perform replacement again.
The sample 1f formed of CLPE containing vitamin E and provided with the polymer film 30 did not reach the wear amount of 1 mg even about 1 × 10 ⁶ times. That is, in the artificial joint using the liner 10 manufactured under the conditions of the sample 1f, there is a possibility that the replacement may be unnecessary for a long time.

(Oxidation experiment)
Two types of oxidation experiments were performed using samples 1d, 1j, and 1k.
In the first oxidation experiment, the oxidation induction time was examined. This measures the time until oxidation starts under conditions where oxidation is likely to occur (heating in an oxidizing atmosphere).
With reference to the ASTM D3895 standard, the time required for each material to undergo an oxidation reaction was measured by differential scanning calorimetry (DSC) to evaluate the antioxidant performance. In the measurement, the temperature was quickly raised to 200 ° C. with nitrogen, and then switched to oxygen gas, and the time from the switching time to the rise of the exothermic peak due to oxidation was defined as the oxidation induction time (OIT). The measurement results are shown in FIG. 9A.
In the samples 1k and 1j in which the substrate 12 did not contain vitamin E, the oxidation reaction started in about 10 seconds from the start of the test. On the other hand, in the sample 1d containing vitamin E as a base material, the oxidation reaction started after 8 minutes or more from the start of the test. By including vitamin E, it was possible to extend the time until the oxidation began by about 50 times.

In the second oxidation experiment, the degree of oxidation was measured. Specifically, the degree of oxidation (oxidation degree) was measured for samples 1d, 1j, and 1k oxidized by an acceleration experiment.
By referring to the ASTM F2003 standard, the test piece was stored in the atmosphere at 80 ° C. for 3 weeks to accelerate the oxidation reaction. About each test piece after an acceleration test, it measured using the transmission micro Fourier infrared spectroscopy (FT-IR) analysis with reference to ASTM F2102 specification. For the measurement, using a Perkin Elmer microscopic FT-IR spectrometer (Spectrum BX), resolution ^{4 cm -1,} integration 100 times, was measured by the transmission method at a wave number 800~4000cm ^-1. From the resulting FT-IR spectrum, main chain -CH 2 of PE _- peak attributable to - click the (1360 cm ^-1 vicinity), near the C = O peak attributed (1680~1750cm ^-1 caused by oxidation ) And the relative degree of oxidation (C = O peak area / -CH ₂ -peak area) was calculated from the ratio. The measurement results are shown in FIG. 9B.

  Samples 1k and 1j in which the substrate 12 did not contain vitamin E had an oxidation degree of 2 to 2.3. On the other hand, the sample 1d containing vitamin E as a base material had an oxidation degree of 0.05 or less. By including vitamin E, the degree of oxidation could be suppressed to about 1/40.

  From the two oxidation experiments, it was found that the substrate 12 having extremely excellent antioxidant property can be obtained by containing vitamin E in the substrate 12.

(Measurement of hydrophilicity (contact angle with water))
In order to investigate the physical properties of the sliding member (liner 10) of the present application, samples 1m to 1r of the hip joint liner 10 as shown in FIG. 2 were prepared. The common manufacturing conditions for each sample are as follows.
[Step 1] A mixed powder was prepared by mixing UHMWPE powder and vitamin E liquid. The content of vitamin E was 0.1% by weight with respect to UHMWPE. The mixed powder was compression molded with a mold to form a base material 12 made of UHMWPE containing vitamin E. The obtained compression-molded body was irradiated with 100 kGy of gamma rays to cause a crosslinking reaction of PE, thereby obtaining a substrate 12 made of CLPE containing vitamin E.
[Step 2] The substrate 12 was immersed in a cleaning solution and washed for 12 hours at a predetermined temperature while stirring.
[Step 3] After washing, the substrate 12 was immersed in an acetone solution (concentration 10 mg / mL) of benzophenone (photopolymerization initiator) for 30 seconds, and then immediately pulled up to remove the solvent on the surface of the substrate 12. In a state where the substrate 12 is immersed in an MPC aqueous solution (concentration 0.5 mol / L, aqueous solution temperature 60 ° C.), ultraviolet light (wavelength 300 to 400 nm) having an intensity of 5.0 mW / cm ² on the sliding surface 16 of the substrate 12. Was irradiated for 90 minutes to form a polymer film (MPC polymer film) 30 grafted to the surface of the sliding surface 16.

In step 2 described above, conditions different for each sample are described below.
(Sample 1m) In Step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as the cleaning liquid, the cleaning temperature was set to room temperature, and the cleaning was performed for 12 hours.
(Sample 1n) In Step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning solution, and cleaning was performed at a cleaning temperature of 40 ° C. and a cleaning time of 12 hours.
(Sample 1o) In Step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning solution, and cleaning was performed at a cleaning temperature of 50 ° C. and a cleaning time of 12 hours.
(Sample 1p) In Step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning solution, and cleaning was performed at a cleaning temperature of 60 ° C. and a cleaning time of 12 hours.
(Sample 1q) In Step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning liquid, and cleaning was performed at a cleaning temperature of 70 ° C. and a cleaning time of 12 hours.
(Sample 1r) In step 2, a Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight was used as a cleaning solution, and cleaning was performed at a cleaning temperature of 80 ° C. and a cleaning time of 12 hours.

With respect to the polymer films 30 provided on the samples 1m, 1n, 1o, 1p, 1q and 1r, the contact angle with water (static contact angle) was examined. The result is shown in FIG.
The sample 1m washed at room temperature had a contact angle exceeding 40 °. Samples 1n, 1o, 1p, 1q, and 1r washed at a washing temperature of 40 ° C. to 80 ° C. had a contact angle of 40 ° or less. In particular, the contact angles of samples 1q and 1r washed at a washing temperature of 70 ° C. to 80 ° C. showed significantly low values.

In order to examine the relationship between the ultraviolet irradiation intensity and the physical properties of the sliding member (liner 10), samples 2a to 2h of the hip joint liner 10 as shown in FIG. 2 were prepared. The common manufacturing conditions for each sample are as follows.
[Step 1] A mixed powder was prepared by mixing UHMWPE powder and vitamin E liquid. The content of vitamin E was 0.1% by weight with respect to UHMWPE. The mixed powder was compression molded with a mold to form a base material 12 made of UHMWPE containing vitamin E. The obtained compression-molded body was irradiated with 100 kGy of gamma rays to cause a crosslinking reaction of PE, thereby obtaining a substrate 12 made of CLPE containing vitamin E.
[Step 2] Substrate 12 was immersed in a cleaning liquid (Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight) and washed for 12 hours while stirring. The washing temperature was 70 ° C.
[Step 3] After washing, the substrate 12 was immersed in an acetone solution (concentration 10 mg / mL) of benzophenone (photopolymerization initiator) for 30 seconds, and then immediately pulled up to remove the solvent on the surface of the substrate 12. In a state where the substrate 12 is immersed in an MPC aqueous solution (concentration 0.5 mol / L, aqueous solution temperature 60 ° C.), the sliding surface 16 of the substrate 12 is irradiated with ultraviolet rays (wavelength 300 to 400 nm) having a predetermined intensity for 90 minutes. Thus, a polymer film (MPC polymer film) 30 grafted to the surface of the sliding surface 16 was formed.

  The intensity of the ultraviolet rays irradiated in the above step 3 was as follows.

(Measurement of hydrophilicity (contact angle with water))
The contact angle (static contact angle) with respect to water was examined for the polymer film 30 provided on the samples 2a to 2h. The measurement conditions were the same as in Example 2. The measurement results are shown in FIG.
The sample 2a not irradiated with ultraviolet rays had a contact angle exceeding 40 °. On the other hand, the contact angle was 40 ° or less for all the samples irradiated with ultraviolet rays (samples 2b to 2h). The contact angle of the polymer film 30 being 40 ° or less suggests that the polymer film 30 has few defects. Therefore, it was found that the polymer film 30 with few defects was formed in all the samples 2b to 2h.

(Phosphate index)
In this example, the density of the polymer film was quantitatively defined using “phosphoric acid index” as a unit for defining the density of the polymer film 30.
Here, the "phosphoric acid index", in the spectrum of FT-IR analysis, a peak intensity I _phosphate 1080 cm ^-1 is the absorption of the phosphate group to the peak intensity I _methylene 1460 cm ^-1 is the absorption of the methylene group Intensity ratio, ie, defined as I _phosphate / I _methylene .

  When a polymer film 30 having a phosphorylcholine group is formed on a base material 12 made of a polymer material (for example, PE) containing a methylene group and subjected to FT-IR measurement, a peak of the methylene group caused by the base material 12; A peak of a phosphate group due to the polymer film 30 is observed. At this time, if the substrate 12 is constant and the film thickness of the polymer film 30 does not change extremely (for example, if the film thickness difference is within 1 μm), the phosphoric acid index calculated from these two peak intensities is This is almost proportional to the number of phosphate groups present per unit area of the substrate 12.

  Patent Documents 4 to 5 describe experimental results regarding the phosphoric acid index and the durability of the liner 10. Specifically, with the liner 10 having a phosphoric acid index of 0.28 or more, the durability is remarkably improved compared to the conventional liner, and it is said that the accelerated experiment has a durability of 5 years or more. Experimental results were obtained. Furthermore, an experimental result was obtained that the liner 10 having a phosphoric acid index of 0.45 or more has a durability of 10 years or more. This can be said to correspond to the number of years in which re-replacement is not necessary over a lifetime when artificial joint replacement is performed after reaching some age.

In this example, the phosphoric acid index was determined for the polymer films 30 of the samples 2a to 2h. For the FT-IR measurement, an FT-IR apparatus FT / IR-6300 type A manufactured by JASCO Corporation was used, and the resolution was 4 cm ⁻¹ and the number of integrations was 64 times. Subsequently, the phosphoric acid group and the methylene group were quantified from the obtained spectrum using a spectrum manager (manufactured by JASCO Corporation), and the phosphoric acid index was calculated. The phosphate index of each sample is shown in FIG.
Sample 2a not irradiated with ultraviolet rays had a phosphoric acid index of less than 0.28. On the other hand, the phosphoric acid index was 0.45 or more in all samples (samples 2b to 2h) irradiated with ultraviolet rays. Therefore, it was found that all the samples 2b to 2h have excellent durability (for example, 10 years or more).

(Film thickness measurement)
The film thickness of the polymer film 30 was determined from the TEM of the cross sections of the samples 2a to 2h. Each sample was embedded in an epoxy resin and stained with ruthenium tetrachloride, and then an ultrathin section was cut out using an ultramicrotome to obtain a sample piece. The sample piece was observed at an acceleration voltage of 100 kV using a transmission electron microscope (JEM-1010 type manufactured by JEOL Ltd.). From the obtained TEM image, the film thickness of the polymer film 30 on the cut surface was measured at 10 points, and the arithmetic average value was calculated. The average film thickness of each sample is shown in FIG.

  The polymer film 30 was not formed on the sample 2a not irradiated with ultraviolet rays. On the other hand, the polymer film 30 having an average film thickness of 100 nm or more was formed in all the samples irradiated with ultraviolet rays (samples 2b to 2h).

(Electron microscope observation)
The cross sections of the samples 2b, 2c, 2e, and 2f were observed with a TEM. The measurement conditions were the same as in Example 3. TEM images of each sample are shown in FIGS.
UV intensity 1.5 mW / cm ² of the sample 2b, 3.5 mW / cm ² of the sample 2e of the specimen 2c and 7.5 mW / cm ^2, the polymeric film 30 having no defects are formed. On the other hand, in the sample 2f having an ultraviolet intensity of 10.0 mW / cm ² , a slight crack and a gap 40 were formed between the polymer film 30 and the base material. From this, it was found that in order to obtain a more durable liner 10, it is preferable to set the intensity of ultraviolet light to less than 10.0 mW / cm ² .

(X-ray photoelectron spectroscopy)
For Samples 2a to 2h, the atomic concentrations of phosphorus atoms and nitrogen atoms in the polymer film 30 were measured using XPS analysis. The measurement conditions were the same as in Example 4. The measurement results are shown in FIG.

In the sample 2a not irradiated with ultraviolet rays, the phosphorus atom concentration of the polymer film 30 was 0 atom%, and the nitrogen atom concentration was 0 atom%. In Sample 2b having an ultraviolet intensity of 1.5 mW / cm ² , the phosphorus atom concentration of the polymer film 30 was 2.9 atom%, and the nitrogen atom concentration was 3.1 atom%. Samples 2c to 2h having an ultraviolet intensity of 3.5 mW / cm ² or higher showed high values of phosphorus atom concentration of 4.2 atom% or higher and nitrogen atom concentration of 3.9 atom% or higher.

In order to examine the relationship between the ultraviolet irradiation time and the physical properties of the sliding member (liner 10), samples 3a to 3i of the hip joint liner 10 as shown in FIG. 2 were prepared. The common manufacturing conditions for each sample are as follows.
[Step 1] A mixed powder was prepared by mixing UHMWPE powder and vitamin E liquid. The content of vitamin E was 0.1% by weight with respect to UHMWPE. The mixed powder was compression molded with a mold to form a base material 12 made of UHMWPE containing vitamin E. The obtained compression-molded body was irradiated with 100 kGy of gamma rays to cause a crosslinking reaction of PE, thereby obtaining a substrate 12 made of CLPE containing vitamin E.
[Step 2] Substrate 12 was immersed in a cleaning liquid (Tween 20 (registered trademark) aqueous solution having a concentration of 1.0% by weight) and washed for 12 hours while stirring. The washing temperature was 70 ° C.
[Step 3] After washing, the substrate 12 was immersed in an acetone solution (concentration 10 mg / mL) of benzophenone (photopolymerization initiator) for 30 seconds, and then immediately pulled up to remove the solvent on the surface of the substrate 12. In a state where the substrate 12 is immersed in an MPC aqueous solution (concentration 0.5 mol / L, aqueous solution temperature 60 ° C.), ultraviolet light (wavelength 300 to 400 nm) having an intensity of 5.0 mW / cm ² on the sliding surface 16 of the substrate 12. Was polymerized for a predetermined time to form a polymer film (MPC polymer film) 30 grafted to the surface of the sliding surface 16.

  In the above step 3, the irradiation time of ultraviolet rays was as follows.

(Measurement of hydrophilicity (contact angle with water))
With respect to the polymer film 30 provided on the samples 3a to 3i, the contact angle with water (static contact angle) was examined. The measurement conditions were the same as in Example 2. The measurement results are shown in FIG.
Sample 3a (unirradiated with ultraviolet rays) to sample 3c (irradiation time 15 minutes) had a contact angle exceeding 40 °. On the other hand, samples 3d (irradiation time: 23 minutes) to 3i (irradiation time: 180 minutes) had a contact angle of 40 ° or less. Therefore, it was found that the polymer film 30 with few defects was formed in all the samples 3d to 3i.

(Phosphate index)
The phosphoric acid index was calculated | required about the polymer film 30 of sample 3a-3i. The measurement conditions were the same as in Example 10. The phosphate index of each sample is shown in FIG.
Sample 3a (non-irradiated with ultraviolet rays) to sample 3b (irradiation time 11 minutes) had a phosphoric acid index of less than 0.28. Sample 3c (irradiation time 15 minutes) had a phosphoric acid index of 0.28 or more and less than 0.45. Samples 3d (irradiation time: 23 minutes) to 3i (irradiation time: 180 minutes) had a phosphoric acid index of 0.45 or more.
Therefore, it was found that the sample 3c has high durability (for example, 5 years or more), and the samples 3d to 3i have excellent durability (for example, 10 years or more).

(Film thickness measurement)
The film thickness of the polymer film 30 was determined from the TEM images of the cross sections of the samples 3a to 3i. The measurement conditions were the same as in Example 11. The average film thickness of each sample is shown in FIG.

  The polymer film 30 was not formed on the sample 3a not irradiated with ultraviolet rays. In Samples 3b to 3d, the film thickness was 100 nm or less, and a hole (uncoated region UC) of the polymer film 30 was observed. In FIG. 19, since the lower end of the error bar has reached a film thickness of 0 nm, it can be seen that there is an uncovered region. Samples 3e (irradiation time 45 minutes) to 3f (irradiation time 60 minutes) had a film thickness of 100 nm or less, but a continuous polymer film 30 was formed. In samples 3g (irradiation time 90 minutes) to 3i (irradiation time 180 minutes), a continuous polymer film 30 having a film thickness of 100 nm or more was formed.

(Electron microscope observation)
The cross sections of Samples 3d and 3e were observed with TEM. The measurement conditions were the same as in Example 3. A TEM image of each sample is shown in FIG.
In the sample 3d having an ultraviolet irradiation time of 23 minutes, the continuous polymer film 30 was not formed, and the uncoated region UC (hole of the polymer film 30) remained. On the other hand, in the sample 3e with an irradiation time of 45 minutes, the polymer film 30 having no defect was formed.

(X-ray photoelectron spectroscopy)
For Samples 3b to 3i, the atomic concentrations of phosphorus atoms and nitrogen atoms in the polymer film 30 were measured using XPS analysis. The measurement conditions were the same as in Example 4. The measurement results are shown in FIG.

In Samples 3b to 3d (irradiation time 11 minutes to 23 minutes) including the uncovered region, the phosphorus atom concentration of the polymer film 30 was 3.7 atom% or less, and the nitrogen atom concentration was 2.5 atom% or less.
In samples 3e to 3i with irradiation times of 45 minutes to 180 minutes, the phosphorus atom concentration was 4 atom% or more and the nitrogen atom concentration was 4 atom% or more.

(Total energy of ultraviolet rays)
Table 3 shows the total energy of ultraviolet rays and the results of TEM images for the samples 1d, 2b, 2c, 2e, 2f, 3d, and 3e. As a result of the TEM observation, when no gap or hole was confirmed in the polymer film 30, it was indicated as “◯”.

In the sample 3d (total energy 6900 mJ / cm ² ), the continuous polymer film 30 was not formed.
Sample 1d (total energy 27000 mJ / cm ² ), sample 2b (total energy 8100 mJ / cm ² ), sample 2c (total energy 18900 mJ / cm ² ), sample 2e (total energy 40500 mJ / cm ² ), sample 3e (total energy 13500 mJ) / Cm ² ), a continuous polymer film 30 was formed.
On the other hand, in sample 2f (total energy 54000 mJ / cm ² ), slight cracks and gaps 40 were formed between the polymer film 30 and the substrate.
These results, the total energy of the irradiated ultraviolet rays is greater than 6900mJ / cm ^2, in the range of less than 54000mJ / cm ^2, was found to be formed is small polymer film defects. In particular, it was found that a polymer film having substantially no defects can be formed if the total energy is 8100 mJ / cm ² or more and 40500 mJ / cm ² or less.

  According to the sliding member (liner 10) according to the present invention, the polymer film 30 formed on the sliding surface 16 of the liner 10 has a contact angle with water of 40 ° or less. It can be seen that there are few defects such as. Therefore, local wear of the liner 10 due to defects in the polymer film 30 hardly occurs, and the liner 10 having a long service life can be obtained.

  Moreover, in the manufacturing method of the sliding member (liner 10) according to the present invention, a step of cleaning at least a part (sliding surface 16) of the surface of the substrate 12 with a cleaning liquid before the formation of the polymer film 30 is performed. By including, the polymer film 30 with few defects such as holes and gaps can be formed on the sliding surface 16. Therefore, local wear of the liner 10 due to defects in the polymer film 30 hardly occurs, and the liner 10 having a long service life can be obtained.

Since the sliding member according to the present invention and the sliding member obtained by the manufacturing method of the present invention both have a long service life, an artificial joint that uses this sliding member to form an artificial joint does not require replacement. A joint or an artificial joint that can reduce the number of revisions can be manufactured.
The disclosure of the present specification may include the following aspects.
(Aspect 1)
A method of manufacturing a sliding member,
Molding a substrate made of a polymer material containing a radical scavenger;
Cleaning at least part of the surface of the substrate with a cleaning liquid;
Forming a polymer film on at least a part of the surface by fixing a polymer chain having a phosphorylcholine group to at least a part of the surface by a graft bond after washing,
The step of forming the polymer film includes sliding that includes irradiating at least part of the surface with ultraviolet light having an intensity of 0.5 mW / cm ² or more in a state where the polymerizable monomer having the phosphorylcholine group is in contact with the surface. Manufacturing method of member.
(Aspect 2)
The manufacturing method according to aspect 1, wherein the ultraviolet rays to be irradiated have an intensity of 3.5 W / cm ² or more and less than 10.0 mW / cm ² .
(Aspect 3)
The manufacturing method of the aspect 1 or 2 including irradiating the said ultraviolet-ray for 45 minutes-180 minutes.
(Aspect 4)
The process according to any one of aspects 1 to 3, wherein the total energy of the irradiated the ultraviolet ray is greater than 54000mJ / cm ² than 6900mJ / cm ^2.
(Aspect 5)
The step of forming the polymer film further includes applying a photopolymerization initiator to at least a part of the surface before the ultraviolet irradiation.
The production method according to any one of aspects 1 to 4, wherein the photopolymerization initiator is excited by irradiation with the ultraviolet light.
(Aspect 6)
The manufacturing method according to any one of aspects 1 to 5, wherein the cleaning liquid is an aqueous solution containing a surfactant.
(Aspect 7)
In the cleaning step, the sliding surface is cleaned at 40 ° C. to 80 ° C. for 6 hours or more, The manufacturing method according to any one of aspects 1 to 6, characterized in that:
(Aspect 8)
The said radical scavenger has a phenolic hydroxyl group or a tocotrienol group, The manufacturing method as described in any one of the aspects 1-7 characterized by the above-mentioned.
(Aspect 9)
9. The production method according to aspect 8, wherein the radical scavenger is vitamin E or a hindered amine compound.
(Aspect 10)
The manufacturing method further includes a step of preparing a polymer material containing the radical scavenger before the step of forming the base material,
The step of preparing the polymer material includes a step of mixing the polymer material powder and the radical scavenger, and compression molding the obtained mixed powder to obtain a polymer material containing the radical scavenger. The manufacturing method as described in any one of the aspects 1-9 characterized by including a process.
(Aspect 11)
In any one of the aspects 1 to 10, the manufacturing method further includes a step of irradiating the polymer material with a high energy ray to crosslink the polymer material before the cleaning step. The manufacturing method of the sliding member of description.

  The present invention is not limited to the artificial hip joint described in the embodiment, but can be applied to various artificial joints such as an artificial spine, an artificial shoulder joint, an artificial knee joint, an artificial elbow joint, an artificial foot joint, and an artificial finger joint. In addition, it is possible to provide an artificial joint with a significantly improved service life.

  1 artificial hip joint, 10 liner, 12 base material, 16 sliding surface, 20 femoral stem, 22 femoral head, 30 polymer membrane, 40 void, UC uncoated region

Claims (9)

A method of manufacturing a sliding member ,
Molding a substrate made of a polymer material containing a radical scavenger;
Cleaning at least part of the surface of the substrate with a cleaning liquid;
Forming a polymer film on at least a part of the surface by fixing a polymer chain having a phosphorylcholine group to at least a part of the surface by a graft bond after washing,
In the washing step, at least a part of the surface is washed at 40 ° C. to 80 ° C. for 6 hours or more,
The cleaning liquid is an aqueous solution containing a nonionic surfactant,
The step of forming the polymer film includes sliding that includes irradiating at least part of the surface with ultraviolet light having an intensity of 0.5 mW / cm ² or more in a state where the polymerizable monomer having the phosphorylcholine group is in contact with the surface. Manufacturing method of member. The manufacturing method according to claim 1, wherein the ultraviolet ray to be irradiated has an intensity of 3.5 W / cm ² or more and less than 10.0 mW / cm ² .   The manufacturing method of Claim 1 or 2 including irradiating the said ultraviolet-ray for 45 minutes-180 minutes. The process according to any one of claims 1 to 3, the total energy of the irradiated the ultraviolet ray is equal to or is greater than 54000mJ / cm ² than 6900mJ / cm ^2. The step of forming the polymer film further includes applying a photopolymerization initiator to at least a part of the surface before the ultraviolet irradiation.
The production method according to claim 1, wherein the photopolymerization initiator is excited by irradiation with the ultraviolet rays. The said radical scavenger has a phenolic hydroxyl group or a tocotrienol group, The manufacturing method of any one of Claims 1-5 characterized by the above-mentioned. The method according to claim 6 , wherein the radical scavenger is vitamin E or a hindered amine compound. The manufacturing method further includes a step of preparing a polymer material containing the radical scavenger before the step of forming the base material,
The step of preparing the polymer material includes a step of mixing the polymer material powder and the radical scavenger, and compression molding the obtained mixed powder to obtain a polymer material containing the radical scavenger. the process according to any one of claims 1 to 7, characterized in that it comprises the steps, a. The manufacturing method, before the step of washing, any one of claim 1 to 8, further comprising the step of crosslinking the polymeric material by irradiation with high-energy radiation to said polymeric material The manufacturing method of the sliding member as described in any one of.