WO2023078165A1 - 超高分子量聚乙烯植入体及其制备方法和人工关节 - Google Patents

超高分子量聚乙烯植入体及其制备方法和人工关节 Download PDF

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WO2023078165A1
WO2023078165A1 PCT/CN2022/128111 CN2022128111W WO2023078165A1 WO 2023078165 A1 WO2023078165 A1 WO 2023078165A1 CN 2022128111 W CN2022128111 W CN 2022128111W WO 2023078165 A1 WO2023078165 A1 WO 2023078165A1
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molecular weight
weight polyethylene
preparation
ultra
approximately
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PCT/CN2022/128111
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English (en)
French (fr)
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俞天白
姚夏睿
梁柱
潘忠诚
常兆华
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苏州微创关节医疗科技有限公司
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/12—Chemical modification
    • C08J7/16—Chemical modification with polymerisable compounds
    • C08J7/18—Chemical modification with polymerisable compounds using wave energy or particle radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J7/00—Chemical treatment or coating of shaped articles made of macromolecular substances
    • C08J7/12—Chemical modification
    • C08J7/123—Treatment by wave energy or particle radiation

Definitions

  • the present application relates to the technical field of medical devices, in particular to an ultra-high molecular weight polyethylene implant, a preparation method thereof, and an artificial joint.
  • Ultra-high molecular weight polyethylene (UHMWPE) is favored by the market for its excellent impact properties, friction resistance and self-lubricating properties, especially in surgical implants. UHMWPE has been used as an artificial joint material for more than 50 years history.
  • ultra-high molecular weight polyethylene has excellent comprehensive properties, as the service life of artificial joints increases, UHMWPE and metal or ceramic hard ends in the artificial joint friction pair will rub for a long time in the body.
  • the fine friction debris produced by UHMWPE can trigger adverse biological reactions, leading to osteolysis and aseptic loosening.
  • the adverse effect of wear debris on artificial joints prompts people to modify materials to achieve the purpose of improving the wear resistance of materials.
  • the present application provides a method for preparing an ultra-high molecular weight polyethylene implant, which includes the following steps:
  • the ultra-high molecular weight polyethylene molding is subjected to electron beam irradiation treatment, and the total irradiation dose of the irradiation treatment is about 20KGy to about 200KGy;
  • the irradiated molded article Under a protective atmosphere, the irradiated molded article is placed in a hydrophilic monomer solution to carry out a grafting reaction under the initiation of free radicals generated by the irradiated treatment, and the temperature of the grafting reaction is is about 50°C to about 80°C, the time is about 30min to about 200min, and the total concentration of the hydrophilic monomer in the hydrophilic monomer solution is about 0.1mol/L to about 1.0mol/L; and
  • Annealing treatment will be carried out through the grafting reaction; the temperature of the annealing treatment is about 110°C to about 160°C, and the time is about 1h to about 10h.
  • the irradiation dose rate of the irradiation treatment is about 1 KGy/s to about 4 KGy/s.
  • the total irradiation dose of the irradiation treatment is about 110 KGy to about 200 KGy.
  • the hydrophilic monomer is selected from at least one of hydroxyethyl acrylate, methacrylic acid, acrylic acid and 2-methacryloyloxyethyl phosphorylcholine.
  • the hydrophilic monomer is selected from one or a mixture of 2-methacryloyloxyethyl phosphorylcholine and hydroxyethyl acrylate.
  • the hydrophilic monomer is a mixture of 2-methacryloyloxyethyl phosphorylcholine and hydroxyethyl acrylate;
  • the molar ratio of 2-methacryloyloxyethyl phosphorylcholine to hydroxyethyl acrylate is 1:0.5-1:5;
  • the molar ratio of 2-methacryloyloxyethyl phosphorylcholine to hydroxyethyl acrylate is 1:1 ⁇ 1:2.
  • the total concentration of the hydrophilic monomer in the hydrophilic monomer solution is about 0.6 mol/L to about 1.0 mol/L.
  • the temperature of the grafting reaction is about 60° C. to about 80° C., and the time is about 40 minutes to about 180 minutes.
  • the temperature of the annealing treatment is about 140° C. to about 150° C., and the time is about 4 hours to about 10 hours.
  • the annealing treatment is performed under vacuum condition or protective atmosphere.
  • the present application also provides an ultra-high molecular weight polyethylene implant, which is prepared by the above-mentioned preparation method.
  • an artificial joint is further provided, the artificial joint includes a first support body (110), a second support body (130) and the ultra-high molecular weight polyethylene implant (120) as described above ;
  • the ultra-high molecular weight polyethylene implant (120) is set between the first support (110) and the second support (130).
  • the ultra-high molecular weight polyethylene implant (120) is in contact with the first support body (110) and the second support body (130) respectively and slides relative to each other.
  • the contact surfaces of the ultra-high molecular weight polyethylene implant (120) and the first support (110) and the second support (130) are all hydrophilic surfaces.
  • the artificial joint is selected from hip joints, knee joints, condyle joints, elbow joints, wrist joints, finger joints or shoulder joints.
  • FIG. 1 is a schematic structural diagram of an artificial joint according to an embodiment of the present application.
  • the first support body 120.
  • the ultra-high molecular weight polyethylene implant 130.
  • the second support body 130.
  • One embodiment of the present application provides an ultra-high molecular weight polyethylene implant and a preparation method thereof.
  • the prepared ultra-high molecular weight polyethylene implant will be described in detail below in conjunction with the preparation method.
  • One embodiment of the present application provides a method for preparing an ultra-high molecular weight polyethylene implant, including the following steps S10, S20 and S30.
  • Step S10 Under a protective atmosphere, subject the ultra-high molecular weight polyethylene molding to electron beam irradiation treatment, and the total irradiation dose of the irradiation treatment is about 20KGy to about 200KGy.
  • the free radicals generated by the decomposition of peroxides and the unsaturated points in the molecules form active centers in chemical cross-linking, and these active centers are connected through monomers to become chemically cross-linked UHMWPE.
  • the matrix material is easily oxidized, which does not meet the requirements for use.
  • electron beam irradiation crosslinking can effectively avoid the risk of oxidation caused by the peroxide crosslinking agent introduced in the chemical crosslinking process.
  • the generated free radicals will be insufficient, which will affect the grafting rate in step S20 and the progress of the crosslinking reaction in step S30. If the total irradiation dose is higher than 200KGy, on the one hand, too many free radicals will be generated. If the annealing is not complete, the residual free radicals will lead to accelerated aging of the product. On the other hand, the molecular chain of UHMWPE may be broken and the molecular weight will be reduced.
  • Step S20 Under a protective atmosphere, place the irradiated molded part in a hydrophilic monomer solution to carry out a grafting reaction under the initiation of free radicals generated by the irradiated treatment.
  • the temperature of the grafting reaction is about 50 °C to about 80°C, the time is about 30 min to about 200 min, and the total concentration of the hydrophilic monomer in the hydrophilic monomer solution is about 0.1 mol/L to about 1.0 mol/L.
  • Step S30 performing annealing treatment after the grafting reaction; the temperature of the annealing treatment is about 110° C. to about 160° C., and the time is about 1 h to about 10 h.
  • the ultra-high molecular weight polyethylene molded part is first subjected to electron beam irradiation treatment under specific conditions, and then the free radicals generated by the irradiation treatment are used to initiate the grafting reaction at a specific temperature.
  • the reaction time is specified, and the irradiation treatment and grafting reaction are controlled successively, and then the remaining free radicals are used to cross-link under specific annealing conditions, so that the surface of the ultra-high molecular weight polyethylene molded part forms a hydrophilic surface, and makes UHMWPE molecules form a three-dimensional network crosslinking structure, which further increases the degree of crosslinking on the surface of the product, thus improving the surface hydrophilicity of the prepared UHMWPE implant, reducing the coefficient of friction, and significantly improving its durability. wear performance.
  • the preparation method of the above ultra-high molecular weight polyethylene implant through process optimization, adopts a one-step electron beam irradiation method to complete the hydrophilic graft modification and crosslinking process, and the process of grafting reaction is simple, without additional use Photoinitiators, acetone solvents, etc., effectively avoid the harm of chemical residues to the human body, and effectively realize hydrophilic grafting; combine the advantages of electron beam irradiation crosslinking and hydrophilic grafting, and synergistically improve the ultra-high molecular weight polyethylene Surface lubricity and wear resistance of implants.
  • the ultra-high molecular weight polyethylene implant is applied to the artificial joint friction pair to reduce the wear rate of the artificial joint during use, thereby reducing the possibility of osteolysis and aseptic loosening, and improving the life of the artificial joint.
  • the above-mentioned preparation method of the ultra-high molecular weight polyethylene implant adopts electron beam irradiation technology, which is a safe and efficient method, and will not cause secondary chemical reagent pollution to the product.
  • the preparation method of the above-mentioned ultra-high molecular weight polyethylene implant in this application avoids the uneven dispersion of cross-linking modification caused by cross-linking degree difference caused by cross-linking agents such as peroxides.
  • cross-linking agents such as peroxides.
  • This preparation method does not need to add cross-linking agents, and is more suitable for the field of artificial joint materials.
  • the irradiation dose rate of the irradiation treatment is about 1 KGy/s to about 4 KGy/s.
  • the total irradiation dose of the irradiation treatment is about 110 KGy to about 200 KGy. Controlling the total irradiation dose within this range can further increase the cross-linking degree of the prepared ultra-high molecular weight polyethylene implant.
  • the hydrophilic monomer is at least one selected from hydroxyethyl acrylate, methacrylic acid, acrylic acid and 2-methacryloyloxyethyl phosphorylcholine (MPC).
  • hydrophilic monomer is selected from one or a mixture of 2-methacryloyloxyethyl phosphorylcholine and hydroxyethyl acrylate.
  • the total concentration of the hydrophilic monomer in the hydrophilic monomer solution is about 0.6 mol/L to about 1.0 mol/L. Controlling the total concentration of the hydrophilic monomer within this range can further improve the surface hydrophilic property of the prepared ultra-high molecular weight polyethylene implant, thereby improving its surface lubricating properties.
  • the temperature of the grafting reaction is about 60° C. to about 80° C., and the time is about 40 minutes to about 180 minutes. Controlling the temperature and duration of the grafting reaction within this range can further improve the surface hydrophilic property of the prepared ultra-high molecular weight polyethylene implant, thereby improving its surface lubricating properties.
  • the temperature of the annealing treatment is about 140° C. to about 150° C., and the time is about 4 hours to about 10 hours. If the heat treatment temperature is too low, the residual free radicals will be bound by molecular chains, the movement ability will be poor, and the free radicals will not be able to recombine, and the purpose of effectively eliminating residual free radicals will not be achieved. Controlling the temperature and duration of the annealing treatment within this range can further increase the degree of crosslinking of the prepared ultra-high molecular weight polyethylene implant, eliminate residual free radicals, prevent residual free radicals from contacting oxygen, and accelerate product aging.
  • the annealing treatment is performed under vacuum condition or protective atmosphere.
  • the protective atmosphere mentioned above includes, but is not limited to, nitrogen and inert gases that do not participate in the reaction.
  • Another embodiment of the present application also provides an ultra-high molecular weight polyethylene implant, which is prepared by the above-mentioned preparation method.
  • another embodiment of the present application further provides an artificial joint, including a first support 110 and the above-mentioned ultra-high molecular weight polyethylene implant 120, the first support 110 and the above-mentioned ultra-high molecular weight polyethylene implant
  • the implants 120 are in contact with each other and slide relative to each other; or include the first support 110, the second support 130 and the above-mentioned ultra-high molecular weight polyethylene implant 120, the first support 110 and the second support 130 are respectively connected with the above-mentioned ultra-high
  • the molecular weight polyethylene implants 120 are in contact with each other and slide relative to each other.
  • the ultra-high molecular weight polyethylene implant body 120 is arranged between the first support body 110 and the second support body 130 .
  • the artificial joint is a hip joint, knee joint, condyle joint, elbow joint, wrist joint, finger joint or shoulder joint. It can be understood that artificial joints include but are not limited thereto.
  • the artificial joint is a hip joint
  • the ultra-high molecular weight polyethylene implant 120 is an acetabular lining
  • the first supporting body 110 and the second supporting body 130 are respectively an acetabular cup prosthesis and a femoral head prosthesis. It can be understood that the contact surfaces of the ultra-high molecular weight polyethylene implant 120 and the first support body 110 and the second support body 130 are all hydrophilic surfaces.
  • the artificial joint can be a knee joint
  • the ultra-high molecular weight polyethylene implant 120 can be a knee joint liner
  • the first supporting body 110 and the second supporting body 130 are femoral condyle prosthesis and tibial tray prosthesis respectively. Others will not be cited one by one.
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint liner sample, and the surface roughness is 0.39 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 1.5KGy/s, and the total irradiation dose is 20KGy.
  • the hydrophilic monomer is a mixed monomer of hydroxyethyl acrylate and 2-methacryloyloxyethyl phosphorylcholine (MPC), the molar ratio of the two monomers is 1:3, and the total monomer concentration is 0.80mol/ L.
  • UHMWPE with a molecular weight of 3.5 million is made into an artificial joint liner sample, and the surface roughness is 0.55 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 4.0KGy/s, and the total irradiation dose is 200KGy.
  • the hydrophilic monomer is 2-methacryloyloxyethyl phosphorylcholine (MPC), and the total monomer concentration is 0.60 mol/L.
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint pad sample, and the surface roughness is 0.90 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 1KGy/s, and the total irradiation dose is 90KGy.
  • the hydrophilic monomer is a mixed monomer of hydroxyethyl acrylate, methacrylic acid and acrylic acid, the molar ratio of the three monomers is 1:1.5:2, and the total monomer concentration is 0.1mol/L.
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint liner sample, and the surface roughness is 0.30 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 2.7KGy/s, and the total irradiation dose is 85KGy.
  • the hydrophilic monomer is a mixed monomer of methacrylic acid and 2-methacryloxyethyl phosphorylcholine (MPC), the molar ratio of the two monomers is 1:1, and the total monomer concentration is 1.0mol/L .
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint gasket sample, and the surface roughness is 0.66 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 3KGy/s, and the total irradiation dose is 110KGy.
  • Example 2 Compared with Example 2, it is basically the same, and the only difference is that the hydrophilic monomer is a mixed monomer of hydroxyethyl acrylate and 2-methacryloyloxyethyl phosphorylcholine (MPC), and the molar ratio of the two monomers is 1 :2, the total monomer concentration is 0.60mol/L.
  • MPC 2-methacryloyloxyethyl phosphorylcholine
  • UHMWPE with a molecular weight of 5 million was made into an artificial joint gasket sample, and the surface roughness was 0.45 ⁇ m, and then it was cleaned and dried.
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint gasket sample, and the surface roughness is 0.57 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 2.5KGy/s, and the total irradiation dose is 95KGy.
  • the annealing temperature is 150°C, and the annealing time is 6h.
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint liner sample, and the surface roughness is 0.41 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 3.1KGy/s, and the total irradiation dose is 10KGy.
  • the hydrophilic monomer is a mixed monomer of hydroxyethyl acrylate and 2-methacryloyloxyethyl phosphorylcholine (MPC), the molar ratio of the two monomers is 1:2, and the total monomer concentration is 1.0mol/ L.
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint pad sample, and the surface roughness is 0.46 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 2.9KGy/s, and the total irradiation dose is 50KGy.
  • the hydrophilic monomer is a mixed monomer of methacrylic acid and 2-methacryloyloxyethyl phosphorylcholine (MPC), the molar ratio of the two monomers is 1:2, and the total monomer concentration is 0.8mol/L .
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint liner sample, and the surface roughness is 0.53 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 1.9KGy/s, and the total irradiation dose is 90KGy.
  • the hydrophilic monomer is a mixed monomer of hydroxyethyl acrylate, methacrylic acid and 2-methacryloyloxyethyl phosphorylcholine (MPC), and the molar ratio of the three monomers is 1:1:2.
  • the total concentration is 0.8mol/L.
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint pad sample, and the surface roughness is 0.55 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 2.4KGy/s, and the total irradiation dose is 80KGy.
  • the irradiated sample was quickly put into the grafting monomer solution, and the grafting reaction was carried out at a temperature of 60° C. under the protection of nitrogen, and the reaction time was 60 minutes.
  • the hydrophilic monomer is a mixed monomer of hydroxyethyl acrylate and 2-methacryloyloxyethyl phosphorylcholine (MPC), the molar ratio of the two monomers is 1:1, and the total monomer concentration is 0.05mol/ L.
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint liner sample, and the surface roughness is 0.50 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 2.5KGy/s, and the total irradiation dose is 100KGy.
  • the hydrophilic monomer is a mixed monomer of methacrylic acid and 2-methacryloyloxyethyl phosphorylcholine (MPC), the molar ratio of the two monomers is 1:1, and the total monomer concentration is 0.7mol/L .
  • UHMWPE with a molecular weight of 5 million is made into an artificial joint pad sample, and the surface roughness is 0.44 ⁇ m, and then it is cleaned and dried. After processing, it is placed in an aluminum foil bag for nitrogen-filled and oxygen-insulated packaging.
  • Electron beam irradiation is carried out on the sample packaged in oxygen barrier, the irradiation dose rate is selected as 2.2KGy/s, and the total irradiation dose is 120KGy.
  • the hydrophilic monomer is a mixed monomer of hydroxyethyl acrylate and 2-methacryloyloxyethyl phosphorylcholine (MPC), the molar ratio of the two monomers is 1:2, and the total concentration of the monomers is 0.6mol/ L.
  • the hydrophilic monomer is 2-methacryloyloxyethyl phosphorylcholine (MPC), and the monomer concentration is 0.6mol/L.
  • the packaged sample is irradiated with an electron beam with a dose rate of 4.0 KGy/s and a total dose of 200 KGy.
  • the surface hydrophilic test object is a sample that has undergone the hydrophilic grafting reaction in step (4) but has not undergone the annealing treatment in step (5).
  • the hydrophilic grafting reaction conditions of Examples 1-6 and Comparative Examples 7-8 are controlled within the above-mentioned range, and better hydrophilic grafting can be obtained, so the samples have smaller water contact angles after the grafting modification step. Among them, the water contact angle of the sample after the graft modification step in Example 6 is the smallest, and the surface hydrophilicity is better.
  • Comparative Example 1 and Comparative Example 2 did not undergo hydrophilic grafting reaction, so the water contact angle was relatively large, and the surface did not have hydrophilic properties.
  • Comparative Example 3 due to the small irradiation dose, the ability to initiate grafting was insufficient, resulting in poor hydrophilicity.
  • Comparative Example 4 it is difficult to form an effective graft because the reaction is carried out at normal temperature.
  • the reaction time of the hydrophilic grafting controlled in Comparative Example 5 was too short, resulting in unsatisfactory hydrophilic grafting effect.
  • the concentration of the grafting monomer in the hydrophilic grafting reaction of Comparative Example 6 was too low to form an effective hydrophilic layer.
  • Comparative Example 9 the direct irradiation method was adopted, and more monomers were directly irradiated for monomer homopolymerization, so the grafting rate was reduced, and the effect of hydrophilic modification was not good.
  • Comparative Example 1 In Comparative Example 1, irradiation crosslinking was not performed, no crosslinking structure was produced, and the swelling degree was relatively large. Comparative examples 2-6 have irradiation and annealing processes, resulting in an effective cross-linked structure with a small degree of swelling. In comparative example 3, the irradiation dose is small, and the overall crosslinking degree after annealing is low. Although Comparative Example 7 and Comparative Example 8 have also been effectively irradiated to produce a cross-linked structure, the annealing temperature of Comparative Example 7 is too low, and the annealing time of Comparative Example 8 is too short, the residual free radicals are bound by molecular chains, and the mobility is low. Poor, free radicals cannot recombine, which is not conducive to the elimination of residual free radicals, so the degree of crosslinking is not high. Comparative Example 9 produced a cross-linked structure through effective irradiation.
  • Examples 1 to 6 all produced effective cross-linked structures with relatively small swelling degrees.
  • Examples 1-6 of the present application have smaller water contact angles and smaller swelling degrees at the same time, indicating that they have better surface hydrophilicity and higher swelling degree. High degree of cross-linking; while Comparative Examples 1-9 cannot simultaneously have a smaller water contact angle and a smaller swelling degree.
  • Anton Paar TRB pin-on-disc friction test device was used to test the friction coefficient and wear rate.
  • the reference standard was ASTM G99-17.
  • CoCrMo was used as the friction pin and UHMWPE was used as the friction disc.
  • calf serum was added as the lubricating fluid for testing.
  • the positive pressure is 70N, and the test frequency is 1Hz.
  • the material of the friction disc is made by using each embodiment and comparative example respectively, so as to test the friction coefficient and wear rate of the samples prepared in each embodiment and comparative example, and the results are shown in Table 4.
  • Example 1 0.049 3.8
  • Example 2 0.041 1.8
  • Example 3 0.055 3.4
  • Example 4 0.047 3.2
  • Example 5 0.051 3.9
  • Example 6 0.036 1.3 Comparative example 1 0.093 10.3 Comparative example 2 0.083 7.1 Comparative example 3 0.079 6.5 Comparative example 4 0.075 6.6 Comparative example 5 0.077 6.1 Comparative example 6 0.073 6.3 Comparative example 7 0.048 6.9 Comparative example 8 0.050 6.8 Comparative example 9 0.075 6.2
  • Comparative Example 1 and Comparative Example 2 The surface of Comparative Example 1 and Comparative Example 2 has no hydrophilic lubricating properties, and the friction coefficient is relatively large; and Comparative Example 1 does not undergo cross-linking reaction, and the wear rate is also high. Comparative examples 3-6 have poor hydrophilic grafting effect and higher coefficient of friction. Comparative Example 2, Comparative Example 3, Comparative Example 4, Comparative Example 5 and Comparative Example 6 have improved the wear resistance of the material due to radiation crosslinking, but the wear rate is higher than that of the effective hydrophilic lubricating layer. sample.
  • Comparative Example 7 and Comparative Example 8 have carried out effective hydrophilic grafting, reduced the surface friction coefficient, and formed a certain cross-linked structure, but did not perform effective annealing treatment, and a large number of remaining free radicals accelerated oxidation during the wear process. increase the wear rate.
  • Comparative Example 9 the direct irradiation method was adopted, and most of the hydrophilic monomers underwent monomer homopolymerization reaction. The actual grafting rate was low, and it was difficult to form an effective hydrophilic lubricating layer, resulting in high friction coefficient and wear rate.
  • the friction coefficient of the samples prepared in Examples 1-6 is small, and the wear rate is also small.
  • the samples prepared in the present application have better surface hydrophilicity and higher degree of cross-linking, thereby improving their wear resistance.

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Abstract

本申请涉及一种超高分子量聚乙烯植入体及其制备方法和人工关节。该制备方法，包括如下步骤：在保护气氛下，将超高分子量聚乙烯成型件进行电子束辐照处理，辐照处理的辐照总剂量为约20KGy～约200KGy；在保护气氛下，将经辐照处理的成型件置于亲水单体溶液中，以在辐照处理产生的自由基的引发下进行接枝反应，接枝反应的温度为约50℃～约80℃，时间为约30min～约200min，亲水单体溶液中亲水单体的总浓度为约0.1mol/L～约1.0mol/L；及将经接枝反应进行退火处理；退火处理的温度为约110℃～约160℃，时间为约1h～约10h。

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超高分子量聚乙烯植入体及其制备方法和人工关节
相关申请
本申请要求2021年11月02日申请的，申请号为2021112906591，名称为“超高分子量聚乙烯植入体及其制备方法和人工关节”的中国专利申请的优先权，在此将其全文引入作为参考。
技术领域
本申请涉及医疗器械技术领域，特别是涉及一种超高分子量聚乙烯植入体及其制备方法和人工关节。
背景技术
超高分子量聚乙烯(UHMWPE)以其优异的冲击性能、耐摩擦性和自润滑性，而受到市场青睐，特别是在外科植入物方面，UHMWPE作为一种人造关节材料已有50余年的使用历史。
虽然超高分子量聚乙烯具有优异的综合性能，但是随着人工关节使用年限的增加，人工关节摩擦副中UHMWPE与金属或者陶瓷硬端在体内会长期摩擦。UHMWPE产生的细小摩擦碎屑会引发不良生物学反应，导致骨溶解，产生无菌松动。磨屑对人工关节的不良影响，促使人们对材料进行改性，以达到提高材料的耐磨损性能的目的。
发明内容
基于此，有必要提供一种具有较佳的耐磨损性能的超高分子量聚乙烯植入体及其制备方法和人工关节。
本申请一方面，提供一种超高分子量聚乙烯植入体的制备方法，其包括如下步骤：
在保护气氛下，将超高分子量聚乙烯成型件进行电子束辐照处理，所述辐照处理的辐照总剂量为约20KGy～约200KGy；
在保护气氛下，将经所述辐照处理的成型件置于亲水单体溶液中，以在所述辐照处理产生的自由基的引发下进行接枝反应，所述接枝反应的温度为约50℃～约80℃，时间为约30min～约200min，所述亲水单体溶液中亲水单体的总浓度为约0.1mol/L～约1.0mol/L；及
将经所述接枝反应进行退火处理；所述退火处理的温度为约110℃～约160℃，时间为 约1h～约10h。
在其中一些实施例中，所述辐照处理的辐照剂量率为约1KGy/s～约4KGy/s。
在其中一些实施例中，所述辐照处理的辐照总剂量为约110KGy～约200KGy。
在其中一些实施例中，所述亲水单体选自丙烯酸羟乙酯、甲基丙烯酸、丙烯酸及2-甲基丙烯酰氧乙基磷酸胆碱中的至少一种。
在其中一些实施例中，所述亲水单体选自2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酸羟乙酯中的一种或二者的混合物。
在其中一些实施例中，所述亲水单体为2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酸羟乙酯中的混合物；
可选地，所述2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酸羟乙酯的摩尔比为1：0.5～1：5；
可选地，所述2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酸羟乙酯的摩尔比为1：1～1：2。
在其中一些实施例中，所述亲水单体溶液中亲水单体的总浓度为约0.6mol/L～约1.0mol/L。
在其中一些实施例中，所述接枝反应的温度为约60℃～约80℃，时间为约40min～约180min。
在其中一些实施例中，所述退火处理的温度为约140℃～约150℃，时间为约4h～约10h。
在其中一些实施例中，所述退火处理在真空条件或保护气氛下进行。
本申请另一方面，还提供一种超高分子量聚乙烯植入体，其采用如上述所述的制备方法制得。
本申请再一方面，进一步提供一种人工关节，所述人工关节包括第一支承体(110)、第二支承体(130)及如上述所述的超高分子量聚乙烯植入体(120)；所述的超高分子量聚乙烯植入体(120)设于所述第一支承体(110)和第二支承体(130)之间。
在其中一些实施例中，所述的超高分子量聚乙烯植入体(120)分别与所述第一支承体(110)和第二支承体(130)相互接触并相对滑动。
在其中一些实施例中，所述的超高分子量聚乙烯植入体(120)与所述第一支承体(110)和第二支承体(130)相互接触的表面均为亲水表面。
在其中一些实施例中，所述人工关节选自髋关节、膝关节、髁关节、肘关节、腕关节、指关节或者肩关节。
本申请的一个或多个实施例的细节在下面的描述中提出。本申请的其它特征、目的和优点将从说明书以及权利要求书变得明显。
附图说明
为了更好地描述和说明这里公开的那些发明的实施例和/或示例，可以参考一幅或多幅附图。用于描述附图的附加细节或示例不应当被认为是对所公开的发明、目前描述的实施例和/或示例以及目前理解的这些发明的最佳模式中的任何一者的范围的限制
图1为本申请一实施例的人工关节的结构示意图。
附图标记：
110、第一支承体；120、超高分子量聚乙烯植入体；130、第二支承体。
具体实施方式
下面将结合本申请实施例中的附图，对本申请实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
除了在操作实施例中所示以外或另外表明之外，所有在说明书和权利要求中表示成分的量、物化性质等所使用的数字理解为在所有情况下通过术语“约”来调整。例如，因此，除非有相反的说明，否则上述说明书和所附权利要求书中列出的数值参数均是近似值，本领域的技术人员能够利用本文所公开的教导内容寻求获得的所需特性，适当改变这些近似值。用端点表示的数值范围的使用包括该范围内的所有数字以及该范围内的任何范围，例如，1～5包括1、1.1、1.3、1.5、2、2.75、3、3.80、4和5等等。
本申请一实施方式提供了一种超高分子量聚乙烯植入体及其制备方法。下文将结合制备方法对制得的超高分子量聚乙烯植入体进行详细的介绍。
本申请一实施方式提供了一种超高分子量聚乙烯植入体的制备方法，包括如下步骤S10、步骤S20和步骤S30。
步骤S10：在保护气氛下，将超高分子量聚乙烯成型件进行电子束辐照处理，辐照处理的辐照总剂量为约20KGy～约200KGy。
从交联原理分析，化学交联由过氧化物分解所生成的自由基与分子中不饱和点生成活性中心，通过单体把这些活性中心连结起来就成为化学交联UHMWPE。化学交联形成的UHMWPE在加速老化过程中，基体材料极易发生氧化，不满足使用要求。相较于传统化学交联，电子束辐照交联能有效避免化学交联过程中引入的过氧化物交联剂带来的氧化风险。
此外，相较于化学交联，物理方式的辐照交联的均匀程度更高，交联程度可由辐照剂 量进行控制，且不需要添加交联剂，更有利地适用于人工关节材料领域。
若辐照总剂量低于20KGy，则生成的自由基不足，会影响步骤S20中的接枝率以及步骤S30中交联反应的进行。若辐照总剂量高于200KGy，一方面生成的自由基过多，如退火不完全，残余自由基会导致产品加速老化，另一方面可能造成超高分子量聚乙烯的分子链断裂，分子量降低。
步骤S20：在保护气氛下，将经辐照处理的成型件置于亲水单体溶液中，以在辐照处理产生的自由基的引发下进行接枝反应，接枝反应的温度为约50℃～约80℃，时间为约30min～约200min，亲水单体溶液中亲水单体的总浓度为约0.1mol/L～约1.0mol/L。
在超高分子量聚乙烯上接枝亲水单体，其几乎不改变超高分子量聚乙烯的骨架结构，同时又将具有各种功能的极性单体接枝到超高分子量聚乙烯的主链上，既保持了原来特性，又增加了新的功能。当亲水单体被接枝到超高分子量聚乙烯聚合物表面形成亲水表面时，是通过化学键与聚合物表面连结，而不仅仅是附着在其上，因此超高分子量聚乙烯聚合物表面上的亲水单体的结合更为牢固，不易随摩擦而断裂。
步骤S30：将经接枝反应进行退火处理；退火处理的温度为约110℃～约160℃，时间为约1h～约10h。
上述超高分子量聚乙烯植入体的制备方法，将超高分子量聚乙烯成型件先于特定条件下进行电子束辐照处理，然后利用辐照处理产生的自由基，引发接枝反应在特定温度反应特定时长，且控制辐照处理和接枝反应先后进行，然后再利用剩余的自由基在特定的退火处理条件下交联，使超高分子量聚乙烯成型件的表面形成亲水表面，且使UHMWPE分子形成了三维网络交联结构，进一步提升产品表面的交联度，如此改善了制得的超高分子量聚乙烯植入体的表面亲水性能，降低了摩擦系数，且显著提升了其耐磨损性能。
上述超高分子量聚乙烯植入体的制备方法，通过工艺的优化，采用一步电子束辐照的方式，完成亲水接枝改性和交联过程，且接枝反应的工艺简单，无需额外使用光引发剂、丙酮溶剂等，有效避免了化学残留对人体的危害，有效地实现了亲水接枝；结合了电子束辐照交联和亲水接枝的优点，协同提升超高分子量聚乙烯植入体的表面润滑特性和耐磨损性能。
该超高分子量聚乙烯植入体应用于人工关节摩擦副中，降低人工关节在使用过程中的磨损率，进而降低骨溶解和无菌松动的可能性，提升人工关节寿命。
上述超高分子量聚乙烯植入体的制备方法，采用电子束辐照技术，是一种安全高效的方法，不会对产品带来二次化学试剂污染。相比于化学交联的方式，本申请上述超高分子量聚乙烯植入体的制备方法，避免了采用过氧化物等交联剂进行交联改性存在的分散不均 造成交联度差异的问题，此外也避免了交联剂分子因其生物学性能在人工关节领域的应用受限的问题，该制备方法不需要添加交联剂，更有适用于人工关节材料领域。
在其中一些实施例中，辐照处理的辐照剂量率为约1KGy/s～约4KGy/s。
进一步可选地，辐照处理的辐照总剂量为约110KGy～约200KGy。辐照总剂量控制在该范围内，可进一步提高制得的超高分子量聚乙烯植入体的交联度。
在其中一些实施例中，亲水单体为选自丙烯酸羟乙酯、甲基丙烯酸、丙烯酸及2-甲基丙烯酰氧乙基磷酸胆碱(MPC)中的至少一种。
进一步地，亲水单体选自2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酸羟乙酯中的一种或二者的混合物。
进一步可选地，亲水单体溶液中亲水单体的总浓度为约0.6mol/L～约1.0mol/L。亲水单体的总浓度控制在该范围内，可进一步提高制得的超高分子量聚乙烯植入体的表面亲水性能，进而提高其表面润滑特性。
进一步可选地，接枝反应的温度为约60℃～约80℃，时间为约40min～约180min。接枝反应的温度和时长控制在该范围内，可进一步提高制得的超高分子量聚乙烯植入体的表面亲水性能，进而提高其表面润滑特性。
进一步可选地，退火处理的温度为约140℃～约150℃，时间为约4h～约10h。如果热处理温度过低，残余自由基被分子链束缚，运动能力较差，自由基不能重新结合，达不到有效消除残余自由基的目的。退火处理的温度和时长控制在该范围内，可进一步提高制得的超高分子量聚乙烯植入体的交联度，且可消除残余自由基，可以防止残余自由基接触氧气，加速产品老化。
在其中一些实施例中，退火处理在真空条件或保护气氛下进行。
可理解，上述任意提及的保护气氛包括不限于不参与反应的氮气、惰性气体。
本申请另一实施方式还提供了一种超高分子量聚乙烯植入体，其采用如上述所述的制备方法制得。
请参阅图1，本申请再一实施方式进一步提供了一种人工关节，包括第一支承体110和上述超高分子量聚乙烯植入体120，第一支承体110和上述超高分子量聚乙烯植入体120相互接触并相对滑动；或者包括第一支承体110、第二支承体130及上述超高分子量聚乙烯植入体120，第一支承体110和第二支承体130分别与上述超高分子量聚乙烯植入体120相互接触并相对滑动。其中，超高分子量聚乙烯植入体120设于第一支承体110和第二支承体130之间。
在其中一些实施例中，人工关节为髋关节、膝关节、髁关节、肘关节、腕关节、指关 节或者肩关节。可理解，人工关节包括但不限于此。
具体地，在图1所示的具体示例中，人工关节为髋关节，超高分子量聚乙烯植入体120为髋臼内衬。第一支承体110和第二支承体130分别为髋臼杯假体和股骨头假体。可理解，超高分子量聚乙烯植入体120与第一支承体110和第二支承体130相互接触的表面均为亲水表面。
在其他示例中，例如人工关节可为膝关节，超高分子量聚乙烯植入体120可为膝关节衬垫。进一步地，第一支承体110和第二支承体130分别为股骨髁假体和胫骨托假体。其他不再一一例举。
为了使本申请的目的、技术方案及优点更加简洁明了，本申请用以下具体实施例进行说明，但本申请绝非仅限于这些实施例。以下所描述的实施例仅为本申请较好的实施例，可用于描述本申请，不能理解为对本申请的范围的限制。应当指出的是，凡在本申请的精神和原则之内所做的任何修改、等同替换和改进等，均应包含在本申请的保护范围之内。
为了更好地说明本申请，下面结合实施例对本申请内容作进一步说明。以下为具体实施例。
实施例1
(1)将分子质量为500万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.39μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择1.5KGy/s，辐照总剂量为20KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在60℃温度氮气保护下进行接枝反应(迅速放入的目的是使接枝反应在辐照处理产生的自由基的引发下进行)，反应时间为180min。其中，亲水单体为丙烯酸羟乙酯和2-甲基丙烯酰氧乙基磷酸胆碱(MPC)混合单体，两种单体摩尔比例为1:3，单体总浓度为0.80mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为120℃，退火时间为5h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
实施例2
(1)将分子质量为350万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.55μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择4.0KGy/s，辐照总剂量为200KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在70℃温度氮气保护下进行接枝反应，反应时间为120min。其中，亲水单体为2-甲基丙烯酰氧乙基磷酸胆碱(MPC)，单体总浓度为0.60mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为140℃，退火时间为10h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
实施例3
(1)将分子质量为500万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.90μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择1KGy/s，辐照总剂量为90KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在50℃温度氮气保护下进行接枝反应，反应时间为30min。其中，亲水单体为丙烯酸羟乙酯、甲基丙烯酸和丙烯酸混合单体，三种单体摩尔比例为1:1.5:2，单体总浓度为0.1mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为110℃，退火时间为6h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
实施例4
(1)将分子质量为500万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.30μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择2.7KGy/s，辐照总剂量为85KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在80℃温度氮气保护下进行接枝反应，反应时间为40min。所述亲水单体为甲基丙烯酸和2-甲基丙烯酰氧乙基磷酸胆碱(MPC)混合单体，两种单体摩尔比例为1:1，单体总浓度为1.0mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为160℃，退火时间为1h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
实施例5
(1)将分子质量为500万的UHMWPE制成人工关节垫片样品，表面粗糙度结果为0.66μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择3KGy/s，辐照总剂量为110KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在50℃温度氮气保护下进行接枝反应，反应时间为200min。其中，亲水单体为丙烯酸羟乙酯，单体总浓度为0.40mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为150℃，退火时间为4h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
实施例6
与实施例2相比，基本相同，区别仅在于亲水单体为丙烯酸羟乙酯和2-甲基丙烯酰氧乙基磷酸胆碱(MPC)混合单体，两种单体摩尔比例为1:2，单体总浓度为0.60mol/L。
对比例1
将分子质量为500万的UHMWPE制成人工关节垫片样品，表面粗糙度结果为0.45μm，然后对其进行清洗干燥处理。
对比例2
(1)将分子质量为500万的UHMWPE制成人工关节垫片样品，表面粗糙度结果为0.57μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择2.5KGy/s，辐照总剂量为95KGy。
(3)将辐照完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为150℃，退火时间为6h。
(4)对退火处理过后的样品进行清洗真空干燥处理。
对比例3
(1)将分子质量为500万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.41μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择3.1KGy/s，辐照总剂量为10KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在80℃温度氮气保护下进行接枝反应，反应时间为40min。其中，亲水单体为丙烯酸羟乙酯和2-甲基丙烯酰氧乙基磷酸胆碱(MPC)混合单体，两种单体摩尔比例为1:2，单体总浓度为1.0mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为150℃，退火时间为1h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
对比例4
(1)将分子质量为500万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.46μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择2.9KGy/s，辐照总剂量为50KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在室温下氮气保护下进行接枝反应，反应时间为60min。其中，亲水单体为甲基丙烯酸和2-甲基丙烯酰氧乙基磷酸胆碱(MPC)混合单体，两种单体摩尔比例为1:2，单体总浓度为0.8mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为150℃，退火时间为2h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
对比例5
(1)将分子质量为500万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.53μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择1.9KGy/s，辐照总剂量为90KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在60℃温度氮气保护下进行接枝反应，反应时间为10min。其中，亲水单体为丙烯酸羟乙酯、甲基丙烯酸和2-甲基丙烯酰氧乙基磷酸胆碱(MPC)混合单体，三种单体摩尔比例为1:1:2，单体总浓度为0.8mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为150℃，退火时间为2.5h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
对比例6
(1)将分子质量为500万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.55μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择2.4KGy/s，辐照总剂量为80KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在60℃温度氮气保护下进行接枝反应，反应时间为60min。所述亲水单体为丙烯酸羟乙酯和2-甲基丙烯酰氧乙基磷酸胆碱(MPC)混合单体，两种单体摩尔比例为1:1，单体总浓度为0.05mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为140℃，退火时间为4h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
对比例7
(1)将分子质量为500万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.50μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择2.5KGy/s，辐照总剂量为100KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在65℃温度氮气保护下进行接枝反应，反应时间为50min。所述亲水单体为甲基丙烯酸和2-甲基丙烯酰氧乙基磷酸胆碱(MPC)混合单体，两种单体摩尔比例为1:1，单体总浓度为0.7mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为90℃，退火时间为3h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
对比例8
(1)将分子质量为500万的UHMWPE制成人工关节衬垫样品，表面粗糙度结果为0.44μm，然后对其进行清洗干燥处理。处理完毕，置于铝箔袋中进行充氮气隔氧包装。
(2)将隔氧包装的样品进行电子束辐照，辐照剂量率选择2.2KGy/s，辐照总剂量为120KGy。
(3)将辐照完的样品迅速放入接枝单体溶液中，在60℃温度氮气保护下进行接枝反应，反应时间为70min。所述亲水单体为丙烯酸羟乙酯和2-甲基丙烯酰氧乙基磷酸胆碱(MPC)混合单体，两种单体摩尔比例为1:2，单体总浓度为0.6mol/L。
(4)将亲水接枝完成的样品置于真空干燥箱进行退火处理，产生三维交联结构。退火温度为150℃，退火时间为0.5h。
(5)对退火处理过后的样品进行清洗真空干燥处理。
对比例9
(直接辐照法)
(1)选取分子质量为350万的UHMWPE，制成人工关节衬垫样品，其表面粗糙度结果在0.50μm，然后进行多次超声清洗，清洗完毕，进行真空干燥。
(2)将清洗干燥后的样品放入接枝单体溶液中，并进行充氮气密封。所述亲水单体为2-甲基丙烯酰氧乙基磷酸胆碱(MPC)，单体浓度为0.6mol/L。
(3)使用剂量率为4.0KGy/s，总剂量为200KGy的电子束对封装的样品进行辐照处理。
(4)对辐照完成的样品进行加热后处理，温度控制在70℃，时间为120min。
(5)将亲水接枝完成的样品置于真空干燥箱进行退火处理，消除残余自由基，产生三维交联结构。退火温度为140℃，退火时间为10h。
(6)对退火处理过后的样品进行清洗真空干燥处理。
各实施例和对比例的部分参数如下表1所示：
表1
Figure PCTCN2022128111-appb-000001
(一)表面亲水测试
将纯水滴(2μL)滴在各实施例和对比例在接枝改性步骤之后的样品表面，并在每次滴加(60s)后用广东北斗精密仪器有限公司PT-705A水接触角仪直接测量水接触角大小。对每个样品进行重复测试10次，并对测得的水接触角值求平均值，得到的结果如下表2所示。以实施例1为例，表面亲水测试对象是经过步骤(4)的亲水接枝反应，但未进行步骤(5)的退火处理的样品。
表2
组别 水接触角
实施例1 24.8°
实施例2 17.9°
实施例3 31.8°
实施例4 21.7°
实施例5 28.5°
实施例6 10.8°
对比例1 75.1°
对比例2 76.5°
对比例3 59.1°
对比例4 60.6°
对比例5 61.1°
对比例6 63.0°
对比例7 24.9°
对比例8 25.3°
对比例9 59.5°
实施例1～6和对比例7～8的亲水接枝反应条件控制在上述范围，能够获得较好的亲水接枝，故而在接枝改性步骤之后样品具有较小的水接触角。其中，实施例6接枝改性步骤之后样品的水接触角最小，表面亲水性较佳。
对比例1和对比例2均未进行亲水接枝反应，故而水接触角较大，表面不具备亲水特性。对比例3由于辐照剂量小，引发接枝能力不足，导致亲水性能不佳。对比例4由于是在常温下进行反应，难以形成有效接枝。对比例5控制的亲水接枝反应时间太短，导致亲水接枝效果不理想。对比例6的亲水接枝反应的接枝单体浓度太低，难以形成有效亲水层。对比例9采用直接辐照法，更多单体直接被辐照进行单体均聚，因此降低了接枝率，亲水改性效果欠佳。
(二)交联溶胀度测试
UHMWPE经过电子束辐照后，分子链的化学键被打断，形成自由基，自由基重新结合形成交联结构。交联后的UHMWPE在其对应的良溶剂中只能发生溶胀，不能溶解。因此，测量溶胀前后的体积变化，可以表征UHMWPE的交联程度。参考YY/T 0813-2010《交联超高分子量聚乙烯(UHMWPE)分子网状结构参数的原位测定标准方法》，采用苏州微创骨科学(集团)有限公司自制溶胀度测试仪POM-HDH8对各实施例和对比例制得的样品的溶胀度进行测试，结果如表3所示。
表3
  溶胀度
实施例1 3.6
实施例2 2.6
实施例3 3.4
实施例4 3.3
实施例5 2.9
实施例6 2.6
对比例1 6.2
对比例2 2.9
对比例3 5.0
对比例4 3.3
对比例5 3.1
对比例6 3.0
对比例7 4.9
对比例8 4.8
对比例9 3.4
对比例1未进行辐照交联，未产生交联结构，溶胀度值较大。对比例2～6有辐照和退火过程，产生了有效的交联结构，溶胀度较小。对比例3辐照剂量较小，退火后整体交联度较低。对比例7和对比例8虽然也进行了有效辐照产生了交联结构，但是对比例7的退火温度太低，对比例8的退火时间太短，残余自由基被分子链束缚，运动能力较差，自由基不能重新结合，不利于消除残余自由基，因此交联程度不高。对比例9经过有效辐照产生了交联结构。
实施例1～6均产生了有效的交联结构，溶胀度较小。
综合上述表面亲水测试和交联溶胀度测试的结果可知，本申请实施例1～6同时具有较小的水接触角和较小的溶胀度，说明其具有较好的表面亲水性和较高的交联度；而对比例1～9无法同时兼具较小的水接触角和较小的溶胀度性能。
(三)摩擦性能测试
使用安东帕TRB销盘摩擦实验装置进行摩擦系数和磨损率测试，参考标准ASTM G99-17，采用CoCrMo作为摩擦销，UHMWPE作为摩擦盘，室温条件下，添加小牛血清作为润滑液进行测试，正压力为70N，测试频率为1Hz。其中，摩擦盘的材质即分别采用各实施例和对比例制得，以测试各实施例和对比例制得的样品的摩擦系数和磨损率，结果如表4所示。
表4
  摩擦系数 磨损率(mg/MC)
实施例1 0.049 3.8
实施例2 0.041 1.8
实施例3 0.055 3.4
实施例4 0.047 3.2
实施例5 0.051 3.9
实施例6 0.036 1.3
对比例1 0.093 10.3
对比例2 0.083 7.1
对比例3 0.079 6.5
对比例4 0.075 6.6
对比例5 0.077 6.1
对比例6 0.073 6.3
对比例7 0.048 6.9
对比例8 0.050 6.8
对比例9 0.075 6.2
对比例1和对比例2表面均没有亲水润滑特性，摩擦系数较大；且对比例1没有进行交联反应，磨损率也很高。对比例3～6亲水接枝效果不佳，摩擦系数较高。对比例2、对比例3、对比例4、对比例5和对比例6由于进行了辐照交联，提升了材料的耐磨损性能，但都磨损率都高于性能有效亲水润滑层的样品。对比例7和对比例8虽然进行了有效亲水接枝，降低了表面摩擦系数，也形成了一定交联结构，但是没有进行有效退火处理，残存的大量自由基在磨损过程中，加速氧化，使得磨损率增大。对比例9采用直接辐照法，亲水单体大多进行单体均聚反应，实际接枝率较低，难以形成有效亲水润滑层，导致摩擦系数和磨损率较高。
实施例1～6制得的样品的摩擦系数较小，其磨损率也较小。综上，本申请制得的样品具有较好的表面亲水性和较高的交联度，进而提升了其耐磨损性能。
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本申请的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对申请专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本申请构思的前提下，还可以做出若干变形和改进，这些都属于本申请的保护范围。因此，本申请专利的保护范围应以所附权利要求为准。

Claims (15)

  1. 一种超高分子量聚乙烯植入体的制备方法，其特征在于，包括如下步骤：
    在保护气氛下，将超高分子量聚乙烯成型件进行电子束辐照处理，所述辐照处理的辐照总剂量为约20KGy～约200KGy；
    在保护气氛下，将经所述辐照处理的成型件置于亲水单体溶液中，以在所述辐照处理产生的自由基的引发下进行接枝反应，所述接枝反应的温度为约50℃～约80℃，时间为约30min～约200min，所述亲水单体溶液中亲水单体的总浓度为约0.1mol/L～约1.0mol/L；及
    将经所述接枝反应进行退火处理；所述退火处理的温度为约110℃～约160℃，时间为约1h～约10h。
  2. 如权利要求1所述的制备方法，其特征在于，所述辐照处理的辐照剂量率为约1KGy/s～约4KGy/s。
  3. 如权利要求1或2所述的制备方法，其特征在于，所述辐照处理的辐照总剂量为约110KGy～约200KGy。
  4. 如权利要求1～3任一项所述的制备方法，其特征在于，所述亲水单体选自丙烯酸羟乙酯、甲基丙烯酸、丙烯酸及2-甲基丙烯酰氧乙基磷酸胆碱中的至少一种。
  5. 如权利要求4所述的制备方法，其特征在于，所述亲水单体选自2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酸羟乙酯中的一种或二者的混合物。
  6. 如权利要求5所述的制备方法，其特征在于，所述亲水单体为2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酸羟乙酯中的混合物；
    可选地，所述2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酸羟乙酯的摩尔比为1：0.5～1：5；
    可选地，所述2-甲基丙烯酰氧乙基磷酸胆碱和丙烯酸羟乙酯的摩尔比为1：1～1：2。
  7. 如权利要求1～6任一项所述的制备方法，其特征在于，所述亲水单体溶液中亲水单体的总浓度为约0.6mol/L～约1.0mol/L。
  8. 如权利要求1～7任一项所述的制备方法，其特征在于，所述接枝反应的温度为约60℃～约80℃，时间为约40min～约180min。
  9. 如权利要求1～8任一项所述的制备方法，其特征在于，所述退火处理的温度为约140℃～约150℃，时间为约4h～约10h。
  10. 如权利要求1～9任一项所述的制备方法，其特征在于，所述退火处理在真空条件或保护气氛下进行。
  11. 一种超高分子量聚乙烯植入体，其特征在于，采用如权利要求1～10任一项所述的 制备方法制得。
  12. 一种人工关节，其特征在于，所述人工关节包括第一支承体(110)、第二支承体(130)及如权利要求11所述的超高分子量聚乙烯植入体(120)；所述的超高分子量聚乙烯植入体(120)设于所述第一支承体(110)和第二支承体(130)之间。
  13. 如权利要求12所述的一种人工关节，其特征在于，所述的超高分子量聚乙烯植入体(120)分别与所述第一支承体(110)和第二支承体(130)相互接触并相对滑动。
  14. 如权利要求13所述的一种人工关节，其特征在于，所述的超高分子量聚乙烯植入体(120)与所述第一支承体(110)和第二支承体(130)相互接触的表面均为亲水表面。
  15. 如权利要求12～14任一项所述的一种人工关节，其特征在于，所述人工关节选自髋关节、膝关节、髁关节、肘关节、腕关节、指关节或者肩关节。
PCT/CN2022/128111 2021-11-02 2022-10-28 超高分子量聚乙烯植入体及其制备方法和人工关节 WO2023078165A1 (zh)

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