WO2022143582A1 - 骨科内固定植入医疗器械 - Google Patents

骨科内固定植入医疗器械 Download PDF

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WO2022143582A1
WO2022143582A1 PCT/CN2021/141841 CN2021141841W WO2022143582A1 WO 2022143582 A1 WO2022143582 A1 WO 2022143582A1 CN 2021141841 W CN2021141841 W CN 2021141841W WO 2022143582 A1 WO2022143582 A1 WO 2022143582A1
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internal fixation
medical device
iron
magnesium
zinc
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French (fr)
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张德元
齐海萍
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Biotyx Medical Shenzhen Co Ltd
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Biotyx Medical Shenzhen Co Ltd
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Priority to CN202180012437.5A priority Critical patent/CN115038470A/zh
Priority to AU2021411660A priority patent/AU2021411660A1/en
Priority to KR1020237021012A priority patent/KR20230125783A/ko
Priority to EP21914318.7A priority patent/EP4268853B1/en
Priority to JP2023535473A priority patent/JP7675189B2/ja
Priority to US18/267,708 priority patent/US20240042108A1/en
Publication of WO2022143582A1 publication Critical patent/WO2022143582A1/zh
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/121—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A61L31/124—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of other specific inorganic materials not covered by A61L31/122 or A61L31/123
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/02—Inorganic materials
    • A61L31/022—Metals or alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • 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
    • A61L27/02—Inorganic materials
    • A61L27/12—Phosphorus-containing materials, e.g. apatite
    • 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
    • A61L27/18—Macromolecular materials obtained otherwise than 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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/42—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix
    • A61L27/425—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having an inorganic matrix of phosphorus containing material, e.g. apatite
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L31/127—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing fillers of phosphorus-containing inorganic materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L31/128—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body

Definitions

  • the invention belongs to the technical field of medical devices, and in particular relates to an orthopaedic internal fixation and implantation medical device.
  • Traditional orthopaedic internal fixation devices are generally made of permanent metals such as stainless steel, titanium-based alloys, and cobalt-based alloys. These materials have excellent mechanical properties and biocompatibility, but long-term storage of these materials in the human body may cause problems such as corrosion, allergy, and osteoporosis due to stress shielding. Removal by a second operation will greatly increase the pain and economic burden of the patient. Therefore, in recent years, absorbable orthopaedic fixtures made of degradable biomedical materials have been extensively studied for clinical use. Compared with permanent metal internal fixation, the most attractive advantage of absorbable orthopaedic internal fixation material is that it does not need to be removed by secondary surgery, which greatly reduces the pain of the patient.
  • the materials for absorbable orthopaedic fixation mainly include absorbable polymers, magnesium and its alloys.
  • Magnesium alloy orthopedic internal fixation material has good biocompatibility and can be degraded in the body, avoiding the pain of secondary surgery, and the released magnesium ions can also promote the proliferation and differentiation of bone cells, and promote bone growth and healing.
  • the elastic modulus of magnesium alloy is close to that of human bone, which can effectively reduce the stress shielding effect.
  • its mechanical properties, such as tensile strength are much higher than those of degradable polymer materials currently used in clinical applications, which can better meet clinical needs.
  • the mechanical properties of magnesium-based alloys still cannot reach the level of permanent metal implant materials, and the clinical application scope is limited, and it is still difficult to apply to load-bearing parts.
  • the degradation rate of magnesium-based alloys is fast, and implanted medical devices will lose effective support and fixation prematurely, and the local pH of the implanted site will increase during the degradation process, and excessive hydrogen bubbles will be generated, which is not conducive to bone damage. of healing.
  • Absorbable polymers such as polylactic acid, polycaprolactone, etc. have good biocompatibility, and a large amount of clinical data has been accumulated. It is processed and molded with high molecular weight polylactic acid, which can produce orthopaedic internal fixation and implantation medical devices with certain mechanical strength.
  • the purpose of the present invention is to provide an orthopaedic internal fixation implanted medical device with better mechanical properties, better control of local pH value, reduction of local inflammatory response, controllable degradation rate, and induction of bone healing.
  • a first aspect of the present invention provides an orthopaedic internal fixation implanted medical device, comprising an iron matrix and a filler material, the filler material comprising polylactic acid and an alkaline substance, wherein the polylactic acid has a weight-average molecular weight of MW kDa , the alkaline substance includes a metal element, the mass ratio of the metal element to the polylactic acid in the alkaline substance is p, and the formula satisfied by the p and the M w is 2M w -0.8 ⁇ p ⁇ 30Mw ⁇ -0.5.
  • the iron matrix in the orthopedic internal fixation implanted medical device can provide sufficient mechanical support, and solves the problem of insufficient mechanical properties of the polylactic acid orthopedic internal fixation medical device and the magnesium alloy orthopedic internal fixation medical device.
  • the filling material includes polylactic acid and an alkaline substance.
  • the alkaline substance can neutralize the acidity of the polylactic acid degradation product in the early stage, and the mass ratio of the metal element in the alkaline substance to the polylactic acid is set to p, and the molecular weight of the polylactic acid is M W kDa,
  • the formula satisfied by p and MW is 2M w ⁇ -0.8 ⁇ p ⁇ 30M w ⁇ -0.5, satisfying this formula can keep the local pH stable, make the pH neutral, can reduce the inflammatory response, is conducive to bone repair, and at the same time The iron matrix degrades at a slower rate in the early stage, allowing it to maintain good mechanical properties during bone healing.
  • the polylactic acid has a weight average molecular weight of 5 kDa to 1000 kDa.
  • the alkaline substance is selected from magnesium, magnesium alloy, zinc, zinc alloy, magnesium oxide, magnesium hydroxide, zinc oxide, zinc hydroxide, magnesium carbonate, zinc carbonate, magnesium phosphate, zinc phosphate, carbonic acid
  • magnesium, magnesium alloy, zinc, zinc alloy, magnesium oxide, magnesium hydroxide, zinc oxide, zinc hydroxide, magnesium carbonate, zinc carbonate, magnesium phosphate, zinc phosphate, carbonic acid One or more of sodium, sodium bicarbonate, calcium oxide, calcium hydroxide, calcium carbonate, calcium phosphate, and hydroxyapatite.
  • the alkaline substance is one or more of powder, granule, block or rod.
  • the alkaline substance is magnesium, magnesium alloy, zinc, zinc alloy, magnesium oxide, magnesium hydroxide, zinc oxide, zinc hydroxide, magnesium carbonate, zinc carbonate, magnesium phosphate, zinc phosphate, sodium carbonate , a composition of at least one of sodium bicarbonate, calcium oxide, calcium hydroxide, calcium carbonate, calcium phosphate and hydroxyapatite. That is, alkaline substances include hydroxyapatite, and also include magnesium, magnesium alloys, zinc, zinc alloys, magnesium oxide, magnesium hydroxide, zinc oxide, zinc hydroxide, magnesium carbonate, zinc carbonate, magnesium phosphate, zinc phosphate, At least one of sodium carbonate, sodium bicarbonate, calcium oxide, calcium hydroxide, calcium carbonate, and calcium phosphate.
  • the mass of the hydroxyapatite is 1-10% of the mass of the orthopaedic internal fixation medical device.
  • the polylactic acid is polyracemic lactic acid or poly-L-lactic acid.
  • the iron matrix is a hollow structure, and the filling material is filled in the inside of the iron matrix; or, the iron matrix is a reticulated skeleton structure, and the filling material is filled in the reticulated skeleton
  • the iron base is a hollow space skeleton structure, and the filling material is filled in the hollow space of the iron base; or, the surface of the iron base is provided with grooves or holes, the filling The material is filled in the grooves or holes of the iron base; or, the filling material is coated on the surface of the iron base.
  • the orthopaedic internal fixation and implantation medical device is a bone nail, a bone plate, a bone rod or a bone mesh.
  • the iron matrix is pure iron, low alloy steel or iron-based alloys with a carbon content not higher than 2.5 wt.%.
  • FIG. 1 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 1.
  • FIG. 1 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 1.
  • FIG. 2 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 3.
  • FIG. 2 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 3.
  • FIG. 3 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 5.
  • FIG. 3 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 5.
  • FIG. 4 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 7.
  • FIG. 4 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 7.
  • FIG. 5 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 9.
  • FIG. 5 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 9.
  • FIG. 6 is a schematic diagram of a cross-section of the orthopaedic internal fixation implanted medical device provided in Example 10.
  • This embodiment provides an orthopaedic internal fixation and implantation medical device, which includes an iron matrix and a filling material, and the filling material includes polylactic acid and an alkaline substance, wherein the weight-average molecular weight of the polylactic acid is MW kDa , and the alkaline substance includes a metal element,
  • the mass ratio of metal element and polylactic acid in the alkaline substance is p, and the formula satisfied by p and M W is 2M w ⁇ -0.8 ⁇ p ⁇ 30M w ⁇ -0.5.
  • Metal elements may include metal cations or metal atoms.
  • the mass ratio p of the metal element in the alkaline substance to the polylactic acid is greater than or equal to 2 times the -0.8 power of the weight-average molecular weight M W of the polylactic acid, and the ratio of the metal element in the alkaline substance to the polylactic acid
  • the mass ratio p is less than or equal to 30 times the weight-average molecular weight M W of the polylactic acid to the power of -0.5.
  • the iron matrix can provide sufficient mechanical support, which solves the problem of insufficient mechanical properties of polylactic acid orthopaedic internal fixation medical devices and magnesium alloy orthopedic internal fixation medical devices.
  • Alkaline substances can neutralize the acidity of polylactic acid degradation products in the early stage.
  • P and M W satisfy the above formula, which can keep the local pH stable, make the pH neutral, reduce the inflammatory response, and be beneficial to bone repair, and at the same time, the iron matrix can be degraded at an early stage. The speed is slowed down so that it maintains good mechanical properties during bone healing.
  • the polylactic acid has a weight average molecular weight of 5 kDa to 1000 kDa.
  • the weight-average molecular weight of the polylactic acid is 100kDa to 500kDa, which makes the acidity of the polylactic acid weaker in the early stage, and at the same time, the degradation period becomes longer, which is beneficial to the accelerated degradation of the iron matrix in the later stage.
  • the alkaline substance is selected from magnesium, magnesium alloy, zinc, zinc alloy, magnesium oxide, magnesium hydroxide, zinc oxide, zinc hydroxide, magnesium carbonate, zinc carbonate, magnesium phosphate, zinc phosphate, sodium carbonate, One or more of sodium bicarbonate, calcium oxide, calcium hydroxide, calcium carbonate, calcium phosphate, and hydroxyapatite.
  • the alkaline substance is selected from magnesium oxide, magnesium hydroxide, zinc oxide, zinc hydroxide, magnesium carbonate, zinc carbonate, magnesium phosphate, zinc phosphate, sodium carbonate, sodium bicarbonate, calcium oxide, calcium hydroxide, calcium carbonate
  • the above oxides or hydroxides or weak acid and strong base salts can avoid the hydrogen bubbles generated by the reaction of these metals of magnesium, magnesium alloys, zinc, zinc alloys with polylactic acid , which is beneficial to tissue growth and repair, and at the same time its alkalinity is lower than that of oxides or hydroxides, and its biocompatibility is better.
  • the alkaline substance is selected from magnesium oxide, magnesium hydroxide, zinc oxide, zinc hydroxide, magnesium carbonate, zinc carbonate, magnesium phosphate, zinc phosphate, sodium carbonate, sodium bicarbonate, calcium oxide, calcium hydroxide, carbonic acid
  • the alkaline substance is one or more of powder, granule, block or rod, so that the alkaline substance can be added to the filling material in various states.
  • the alkaline substance includes hydroxyapatite, and the mass of the hydroxyapatite is 1-10% of the mass of the orthopaedic internal fixation medical device.
  • the polylactic acid is polylactic acid or poly-L-lactic acid.
  • the iron matrix is pure iron, low alloy steel or an iron-based alloy with a carbon content not higher than 2.5 wt.%.
  • the low alloy steel is the alloy steel with the total amount of alloy elements less than 5%.
  • the iron matrix is nitrided iron, and the carbon content in the nitrided iron is less than or equal to 0.25%, which is an iron-based alloy with a carbon content not higher than 2.5wt.%. Iron nitride has better mechanical properties.
  • connection relationship between the iron matrix and the filling material has various forms.
  • the iron matrix is a hollow structure, and the filling material is filled in the interior of the iron matrix; or, the iron matrix is a reticulated skeleton structure, and the filling material is filled in the mesh holes of the reticulated skeleton structure; or, the iron matrix is a hollow space skeleton structure, filled with
  • the material is filled in the hollow space of the iron base; alternatively, the surface of the iron base is provided with grooves or holes, and the filling material is filled in the grooves or holes of the iron base; or, the filling material is coated on the surface of the iron base.
  • the shape of the iron matrix is nail-like, mesh-like, plate-like, rod-like, cylindrical, cubic or conical.
  • the orthopaedic internal fixation and implantation medical device may be a bone nail, a bone plate, a bone rod or a bone mesh.
  • test methods involved in the following examples are as follows:
  • the molecular weight measurement system was used to detect the GPC-multi-angle laser light scattering instrument of Wyatt Company in the United States.
  • the test system includes a liquid phase pump and injector from Agilent, USA, an Agilent PL MIXED-C GPC column (size: 7.5 ⁇ 300mm, 5 microns) from Agilent, a multi-angle laser light scattering instrument from Wyatt, and Differential detector.
  • the detection conditions are:
  • Mobile phase tetrahydrofuran; pump flow rate: 1 mL/min; injection volume: 100 ⁇ L; laser wavelength: 663.9 nm; test temperature: 35°C.
  • the weighed orthopaedic internal fixation and implantation medical device is placed in a solvent (such as ethyl acetate, chloroform, etc.) that can dissolve polylactic acid, ultrasonically cleaned for 30 minutes, filtered, and the filtrate is dried and weighed.
  • a solvent such as ethyl acetate, chloroform, etc.
  • the quality difference before and after cleaning is the quality of polylactic acid.
  • XRD XRD was used to detect orthopaedic internal fixation and implanted medical devices, and compared with iron, hydroxyapatite, magnesium, zinc, magnesium oxide, zinc oxide, magnesium hydroxide, zinc hydroxide, magnesium carbonate, zinc carbonate, magnesium phosphate, zinc phosphate, Standard maps of sodium carbonate, sodium bicarbonate, calcium oxide, calcium hydroxide, calcium carbonate, calcium phosphate, etc., can determine the phase of alkaline substances.
  • the concentration of magnesium ion or zinc ion or calcium ion or sodium ion in the digestion solution was determined by AAS.
  • the mass of metal elements in basic substances in orthopaedic internal fixation and implantation medical devices can be obtained by calculation.
  • the C43.504 universal material testing machine produced by MTS company was used to test the three-point bending strength of the sample according to the YBT5349-2006 test standard for bending mechanical properties of metal materials.
  • Corrosion of iron-based matrices was assessed by mass loss rate after absorbable iron-based orthopaedic implants for medical devices implanted in animals. Specifically, the following steps are included: implanting an absorbable iron-based orthopaedic internal fixation device with an iron-based matrix mass of M0 into an animal body. Then at predetermined observation time points, such as 3 months, 6 months, 12 months, etc., remove the device and its surrounding tissue, and soak the tissue together with the device in 1 mol/L sodium hydroxide solution to remove the remaining degradable polyester and disintegrate the tissue.
  • predetermined observation time points such as 3 months, 6 months, 12 months, etc.
  • the mass loss rate W of the iron-based matrix at a certain observation time point is less than 5%, it is considered that the iron-based matrix is not corroded in the time range from the implantation time point to the observation time point.
  • the mass loss rate W of the iron-based matrix at a certain observation time point is greater than or equal to 90%, the iron-based matrix is considered to be completely corroded, and the time zone between the implantation time point and the observation time point is the corrosion period of the iron-based matrix. .
  • the initial bending strength of the bone nail is 350MPa.
  • the bone nails were implanted into animals and taken out after 6 months, and the iron was degraded by 10%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopaedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 7-8.
  • the weight average molecular weight of poly-L-lactic acid is 1000kDa
  • the mass ratio of magnesium element to poly-L-lactic acid is 0.008.
  • the mass of hydroxyapatite is 1% of the entire orthopaedic internal fixation implanted medical device.
  • the initial bending strength of the bone nail is 350MPa.
  • the bone nails were implanted into animals and taken out after 6 months, and the iron was degraded by 17%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 6-7.
  • the absorbable iron-based bone nail is obtained by coating on the surface of the nail-shaped iron base body 21 , and its cross-section is shown in FIG. 2 .
  • the weight-average molecular weight of the polyracemic lactic acid is 500 kDa
  • the mass ratio of zinc element to the polyracemic lactic acid is 1.3
  • the mass of hydroxyapatite is 3% of the entire orthopaedic internal fixation implanted medical device.
  • the initial bending strength of the bone nail is 450MPa.
  • the bone nails were implanted into animals and taken out after 6 months, and the iron was degraded by 15%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 7-8.
  • the pure iron is cast into a nail shape with grooves on the surface, and its strength is enhanced by ion nitriding to obtain a nail-shaped iron matrix; magnesium hydroxide powder and hydroxyapatite powder are dispersed in molten poly-L-lactic acid, and the The mixture is coated on the surface of the nail-shaped iron base to obtain an absorbable iron-based bone nail.
  • the weight average molecular weight of poly-L-lactic acid is 500kDa
  • the mass ratio of magnesium element to poly-L-lactic acid is 0.014.
  • the mass of hydroxyapatite is 3% of the entire orthopaedic internal fixation implanted medical device.
  • the initial bending strength of the bone nail is 420MPa.
  • the bone nails were implanted into animals and taken out after 6 months, and the iron was degraded by 18%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 6-7.
  • the low-alloy steel is cast into a hollow nail-like shape 31, and the interior of the nail also includes an iron support rod 32 parallel to the iron nail, the cross-section of which is shown in FIG. 3 .
  • the iron nails were cut into hollow lumen structures with a laser cutter.
  • the magnesium oxide powder and the hydroxyapatite powder are dispersed in the molten polyracemic lactic acid, and the mixture 33 is filled in the iron matrix to obtain an absorbable iron-based bone nail.
  • the weight-average molecular weight of the polyracemic lactic acid is 100 kDa
  • the mass ratio of magnesium element to the polyracemic lactic acid is 0.05.
  • the mass of hydroxyapatite is 10% of the entire orthopaedic internal fixation implanted medical device.
  • the initial bending strength of the bone nail is 380MPa.
  • the bone nails were implanted into animals and taken out after 6 months, and the iron was degraded by 25%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 6-7.
  • the low-alloy steel is cast into a hollow rod-shaped surface with holes to obtain a rod-shaped iron matrix.
  • Small zinc rods and hydroxyapatite powder are dispersed in molten polyracemic lactic acid, and the mixture is filled in iron rods to obtain absorbable iron-based bone rods.
  • the weight-average molecular weight of the polyracemic lactic acid is 100 kDa
  • the mass ratio of zinc element to the polyracemic lactic acid is 3.
  • the mass of hydroxyapatite is 10% of the entire orthopaedic internal fixation implanted medical device.
  • the initial bending strength of the bone rod is 480MPa.
  • the bone nails were implanted in animals and taken out after 6 months, the iron was degraded by 18%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopaedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 7-8.
  • a mesh iron matrix 41 Take a piece of pure iron and cut it into a mesh shape with a laser cutting machine to obtain a mesh iron matrix 41 .
  • the weight-average molecular weight of the poly(racemic lactic acid) is 5 kDa
  • the mass ratio of the zinc element to the poly(racemic lactic acid) is 0.55.
  • the mass of hydroxyapatite is 6% of the entire orthopaedic internal fixation implanted medical device.
  • the initial bending strength of the bone mesh was 350 MPa.
  • the bone nails were implanted into animals and taken out after 6 months, and the iron was degraded by 20%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 6-7.
  • the zinc powder and the hydroxyapatite powder are dispersed in the molten polyracemic lactic acid, and the mixture is coated on the surface and the mesh holes of the iron mesh to obtain an iron-based absorbable bone mesh.
  • the weight-average molecular weight of polylactide is 5kDa
  • the mass ratio of zinc element to polylactic acid is 13.4.
  • the mass of hydroxyapatite is 6% of the entire orthopaedic internal fixation implanted medical device.
  • the initial bending strength of the bone mesh was 500 MPa.
  • the bone nails were implanted into animals and taken out after 6 months, and the iron was degraded by 14%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopaedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 7-8.
  • the iron wire with the zinc layer on the hollow surface is taken and woven into an iron mesh to obtain a mesh iron matrix 51 .
  • Zinc oxide powder and hydroxyapatite powder are dispersed in the molten polyracemic lactic acid, and the mixture 52 is coated on the surface of the iron mesh and in the mesh to obtain an absorbable iron-based bone mesh, as shown in Figure 5 .
  • the weight-average molecular weight of the polyracemic lactic acid is 200 kDa
  • the mass ratio of zinc element to the polyracemic lactic acid is 0.03.
  • the mass of hydroxyapatite is 7% of the entire orthopaedic internal fixation implanted medical device.
  • the initial bending strength of the bone mesh was 420 MPa.
  • the bone nails were implanted into animals and taken out after 6 months, and the iron was degraded by 27%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 6-7.
  • the initial bending strength of the bone mesh was 600 MPa.
  • the bone nails were implanted into animals and taken out after 6 months, and the iron was degraded by 20%.
  • the orthopaedic internal fixation implanted medical device was soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopaedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 7-8.
  • Poly-L-lactic acid absorbable bone nail the molecular weight of poly-L-lactic acid is 500kDa.
  • the initial bending strength of the bone nail is 150MPa.
  • the absorbable bone nails were soaked in PBS solution, and after 7 days of water bath at 37°C, the orthopaedic internal fixation implanted medical device was taken out, and the pH value of the surface of the device was immediately detected by pH test paper to be 4-5.

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Abstract

本发明属于医疗器械技术领域，具体涉及一种骨科内固定植入医疗器械，包括铁基体和填充材料，填充材料包括聚乳酸和碱性物质，其中，聚乳酸重均分子量为MWkDa，碱性物质包括金属元素，碱性物质中金属元素与聚乳酸的质量比为p，p与MW满足的公式为2Mw^-0.8≤p≤30Mw^-0.5。该骨科内固定植入医疗器械的力学性能较好，能较好地控制局部pH值，同时其能诱导骨愈合。

Description

骨科内固定植入医疗器械 技术领域
本发明属于医疗器械技术领域，具体涉及一种骨科内固定植入医疗器械。
背景技术
传统的骨科内固定器械一般由不锈钢、钛基合金及钴基合金等永久性金属制成。这些材料具有优异的力学性能和生物相容性，但这些材料长期存留在人体中可能会存在蚀损、过敏、因应力遮挡作用而导致骨质疏松等问题，这就需要在病人骨折愈合后进行二次手术取出，会大大增加患者的痛苦和经济负担。因此，近年来，由可降解生物医用材料制成的可吸收骨科固定物被广泛研究，用于临床。与永久性金属内固定物相比，可吸收骨科内固定材料最具有吸引力的优势是：无需二次手术取出，大大减轻了病人痛苦。
目前，可吸收骨科固定物用材料主要包括可吸收聚合物、镁及其合金。
镁合金骨科内固定材料具有良好的生物相容性，可在体内降解，避免二次手术取出的痛苦，且其释放出的镁离子还可以促进骨细胞的增殖机分化，促进骨骼生长、愈合。镁合金弹性模量与人骨接近，可以有效降低应力遮挡效应，同时其力学性能，如拉伸强度等远高于目前临床应用的可降解高分子聚合物材料，可以更好地满足临床需求。但镁基合金的力学性能仍达不到永久性金属植入材料的水平，临床应用范围有限，仍难以应用于承力部位，目前只能用于非承重和活动较少的位置。其次，镁基合金降解速率较快，植入医疗器械会过早丧失有效支撑和固定作用，且降解过程中会使植入部位局部pH增高，且产生过多的氢气泡，不利于骨头损伤部位的愈合。
可吸收聚合物如聚乳酸、聚已内酯等具有良好的生物相容性，已经积累了大量的临床数据。用高分子量的聚乳酸熔融后再加工成型，可以制作具有一定力学强度的骨科内固定植入医疗器械。与传统的永久性金属材料相比，其不足之处有：(1)骨传导性差，修复骨缺损的速度很慢，对于较大的骨质缺损，难以达到完全骨修复；(2)力学性能差，机械强度不足，通常不能应用于承力部位(如四肢)，仅适用于各种非承重部位的松质骨、关节骨或活动较少的骨的固定；(3)早期降解速度较快，以至于无法保证满足在新的骨组织生长出来之前力学性能要求；(4)聚乳酸降解会产生酸性环境，容易导致植入部位产生较严重的炎症反应。这些缺点都大大的制约了可吸收聚合物基内固定植入医疗器械 的应用。聚乳酸产生的局部微酸性环境以及在骨诱导能力方面尚有较大的进步空间。
发明内容
本发明的目的是提供一种力学性能较好，能较好地控制局部pH值，减少局部炎症反应，降解速度可控，同时能诱导骨愈合的骨科内固定植入医疗器械。
本发明的第一方面提出了一种骨科内固定植入医疗器械，包括铁基体和填充材料，所述填充材料包括聚乳酸和碱性物质，其中，所述聚乳酸重均分子量为M W kDa，所述碱性物质包括金属元素，所述碱性物质中所述金属元素与所述聚乳酸的质量比为p，所述p与所述M W满足的公式为2M w^-0.8≤p≤30M w^-0.5。
上述骨科内固定植入医疗器械中铁基体能够提供足够的力学支撑，解决了聚乳酸骨科内固定医疗器械和镁合金骨科内固定医疗器械力学性能不足的问题。填充材料包括聚乳酸和碱性物质，碱性物质可以在早期中和聚乳酸降解产物的酸性，并且设置碱性物质中金属元素与聚乳酸的质量比为p，聚乳酸分子量为M W kDa，p与M W满足的公式为2M w^-0.8≤p≤30M w^-0.5，满足该公式，可保持局部pH稳定，使pH呈中性，能够减少炎症反应，有利于骨修复，同时使铁基体早期降解速度变慢，使其在骨愈合期间保持良好的力学性能。
在一实施例中，所述聚乳酸的重均分子量为5kDa～1000kDa。
在一实施例中，所述碱性物质选自镁、镁合金、锌、锌合金、氧化镁、氢氧化镁、氧化锌、氢氧化锌、碳酸镁、碳酸锌、磷酸镁、磷酸锌、碳酸钠、碳酸氢钠、氧化钙、氢氧化钙、碳酸钙、磷酸钙、羟基磷灰石中的一种或多种。
在一实施例中，所述碱性物质为粉末状、颗粒状、块状或棒状中的一种或多种。
在一实施例中，所述碱性物质为镁、镁合金、锌、锌合金、氧化镁、氢氧化镁、氧化锌、氢氧化锌、碳酸镁、碳酸锌、磷酸镁、磷酸锌、碳酸钠、碳酸氢钠、氧化钙、氢氧化钙、碳酸钙、磷酸钙中的至少一种和羟基磷灰石的组合物。即碱性物质中包括羟基磷灰石，同时还包括镁、镁合金、锌、锌合金、氧化镁、氢氧化镁、氧化锌、氢氧化锌、碳酸镁、碳酸锌、磷酸镁、磷酸锌、碳酸钠、碳酸氢钠、氧化钙、氢氧化钙、碳酸钙、磷酸钙中的至少一种。
在一实施例中，所述羟基磷灰石的质量为所述骨科内固定医疗器械的质量的1～10％。
在一实施例中，所述聚乳酸为聚消旋乳酸或聚左旋乳酸。
在一实施例中，所述铁基体为中空结构，所述填充材料填充于所述铁基体的内部；或者，所述铁基体为网状骨架结构，所述填充材料填充于所述网状骨架结构的网孔中；或者，所述铁基体为镂空空间骨架结构，所述填充材料填充于所述铁基体的镂空空间内部；或者，所述铁基体表面设有凹槽或孔洞，所述填充材料填充于所述铁基体的凹槽或孔洞中；或者，所述填充材料涂覆于所述铁基体表面。
在一实施例中，所述骨科内固定植入医疗器械为骨钉、骨板、骨棒或骨网。
在一实施例中，所述铁基体为纯铁、低合金钢或碳含量不高于2.5wt.％的铁基合金。
附图说明
通过阅读下文优选实施方式的详细描述，各种其它的优点和益处对于本领域普通技术人员将变得清楚明了。附图仅用于示出优选实施方式的目的，而并不认为是对本发明的限制。而且在整个附图中，用相同的附图标记表示相同的部件。其中：
图1为实施例1提供的骨科内固定植入医疗器械的横截面的示意图。
图2为实施例3提供的骨科内固定植入医疗器械的横截面的示意图。
图3为实施例5提供的骨科内固定植入医疗器械的横截面的示意图。
图4为实施例7提供的骨科内固定植入医疗器械的横截面的示意图。
图5为实施例9提供的骨科内固定植入医疗器械的横截面的示意图。
图6为实施例10提供的骨科内固定植入医疗器械的横截面的示意图。
具体实施方式
下面将参照附图更详细地描述本发明的示例性实施方式。虽然附图中显示了本发明的示例性实施方式，然而应当理解，可以以各种形式实现本发明而不应被这里阐述的实施方式所限制。相反，提供这些实施方式是为了能够更透彻地理解本发明，并且能够将本发明的范围完整的传达给本领域的技术人员。
应理解的是，文中使用的术语仅出于描述特定示例实施方式的目的，而无意于进行限制。除非上下文另外明确地指出，否则如文中使用的单数形式“一”、“一个”以及“所述”也可以表示包括复数形式。术语“包括”、“包含”、“含 有”以及“具有”是包含性的，并且因此指明所陈述的特征、步骤、操作、元件和/或部件的存在，但并不排除存在或者添加一个或多个其它特征、步骤、操作、元件、部件、和/或它们的组合。文中描述的方法步骤、过程、以及操作不解释为必须要求它们以所描述或说明的特定顺序执行，除非明确指出执行顺序。还应当理解，可以使用另外或者替代的步骤。
本实施例提供一种骨科内固定植入医疗器械，包括铁基体和填充材料，填充材料包括聚乳酸和碱性物质，其中，聚乳酸重均分子量为M W kDa，碱性物质包括金属元素，碱性物质中金属元素与聚乳酸的质量比为p，p与M W满足的公式为2M w^-0.8≤p≤30M w^-0.5。金属元素可以包括金属阳离子或者金属原子。该公式用文字表达成：碱性物质中金属元素与聚乳酸的质量比p大于或等于2倍的聚乳酸重均分子量M W的-0.8次方，并且碱性物质中金属元素与聚乳酸的质量比p小于或等于30倍的聚乳酸重均分子量M W的-0.5次方。
其中，铁基体能够提供足够的力学支撑，解决了聚乳酸骨科内固定医疗器械和镁合金骨科内固定医疗器械力学性能不足的问题。碱性物质可以在早期中和聚乳酸降解产物的酸性，p与M W满足上述公式，可保持局部pH稳定，使pH呈中性，减少炎症反应，有利于骨修复，同时使铁基体早期降解速度变慢，使其在骨愈合期间保持良好的力学性能。
在一实施例中，聚乳酸的重均分子量为5kDa～1000kDa。优选的，聚乳酸的重均分子量为100kDa～500kDa，使聚乳酸的早期酸性较弱，同时降解周期变长，有利于后期铁基体的加速降解。
在一实施例中，碱性物质选自镁、镁合金、锌、锌合金、氧化镁、氢氧化镁、氧化锌、氢氧化锌、碳酸镁、碳酸锌、磷酸镁、磷酸锌、碳酸钠、碳酸氢钠、氧化钙、氢氧化钙、碳酸钙、磷酸钙、羟基磷灰石中的一种或多种。优选的，碱性物质选自氧化镁、氢氧化镁、氧化锌、氢氧化锌、碳酸镁、碳酸锌、磷酸镁、磷酸锌、碳酸钠、碳酸氢钠、氧化钙、氢氧化钙、碳酸钙、磷酸钙、羟基磷灰石中的一种或多种，其中上述氧化物或氢氧化物或弱酸强碱盐可以避免镁、镁合金、锌、锌合金这些金属与聚乳酸反应生成的氢气泡，从而有利于组织生长修复，同时其碱性又低于氧化物或氢氧化物，生物相容性更好。优选的，碱性物质为选自氧化镁、氢氧化镁、氧化锌、氢氧化锌、碳酸镁、碳酸锌、磷酸镁、磷酸锌、碳酸钠、碳酸氢钠、氧化钙、氢氧化钙、碳酸钙、磷酸钙中的至少一种与羟基磷灰石的组合物，其中，羟基磷灰石用于提高生物活 性，促进骨愈合。
在一实施例中，碱性物质为粉末状、颗粒状、块状或棒状一种或多种，方便碱性物质以各种状态加入至填充材料中。
在一实施例中，碱性物质包括羟基磷灰石，羟基磷灰石的质量为骨科内固定医疗器械的质量的1～10％。
在一实施例中，聚乳酸为聚消旋乳酸或聚左旋乳酸。
在一实施例中，铁基体为纯铁、低合金钢或碳含量不高于2.5wt.％的铁基合金。其中，低合金钢为合金元素总量小于5％的合金钢。优选的，铁基体为渗氮铁，渗氮铁中碳含量≤0.25％，属于碳含量不高于2.5wt.％的铁基合金。渗氮铁具有更好的力学性能。
在本发明实施例中，铁基体和填充材料之间的连接关系有多种形式。铁基体为中空结构，填充材料的填充于铁基体的内部；或者，铁基体为网状骨架结构，填充材料填充于网状骨架结构的网孔中；或者，铁基体为镂空空间骨架结构，填充材料填充于铁基体的镂空空间内部；或者，铁基体表面设有凹槽或孔洞，填充材料填充于铁基体的凹槽或孔洞中；或者，填充材料涂覆于铁基体表面。
其中，铁基体的形状为钉状、网状、板状、棒状、圆柱形、立方形或锥形。
本发明实施例中骨科内固定植入医疗器械可以为骨钉、骨板、骨棒或骨网。
以下通过具体实施例对上述医疗器械进一步阐述。
以下实施例中涉及的测试方式如下：
1、聚乳酸的重均分子量测定
使用美国Wyatt公司的GPC-多角度激光光散射仪联用分子量测试系统进行检测。该测试系统包括美国安捷伦公司的液相泵和进样器、美国安捷伦公司的Agilent PL MIXED-C型GPC柱(尺寸：7.5×300mm，5微米)、美国Wyatt公司的多角度激光光散射仪及示差检测器。检测条件为：
流动相：四氢呋喃；泵流速：1mL/min；进样量：100μL；激光波长：663.9nm；测试温度：35℃。
2、聚乳酸质量
将已称重的骨科内固定植入医疗器械置于可溶解聚乳酸的溶剂中(如乙酸乙酯、氯仿等)，超声清洗30分钟后过滤，将滤出物干燥后称重。清洗前后的 质量差即为聚乳酸的质量。
3、碱性物质的物相鉴别
采用XRD检测骨科内固定植入医疗器械，并对照铁、羟基磷灰石、镁、锌、氧化镁、氧化锌、氢氧化镁、氢氧化锌、碳酸镁、碳酸锌、磷酸镁、磷酸锌、碳酸钠、碳酸氢钠、氧化钙、氢氧化钙、碳酸钙、磷酸钙等的标准图谱，可确定碱性物质的物相。
4、碱性物质中金属元素的质量
将骨科内固定植入医疗器械用硝酸消解后，用AAS测定消解液中的镁离子或锌离子或钙离子或钠离子的浓度。通过计算可获得骨科内固定植入医疗器械中碱性物质中金属元素的质量。
5、抗弯曲强度
采用MTS公司生产的C43.504型号的万能材料试验机，根据YBT5349-2006金属材料弯曲力学性能试验标准对试样的三点弯曲强度进行测试。
6、铁的降解速率
在可吸收铁基骨科内固定植入医疗器械植入动物体内后，铁基基体的腐蚀情况通过质量损失率评估。具体包括以下步骤：将铁基基体质量为M0的可吸收铁基骨科内固定植入医疗器械植入动物体内。然后在预定观察时间点，诸如3个月、6个月、12个月等，取出器械及其周边组织，将组织连同器械浸泡在1mol/L氢氧化钠溶液中，以去除剩余可降解聚酯并使组织消解。然后从氢氧化钠溶液中取出器械，将其放入3％酒石酸溶液中超声，使器械上附着的腐蚀产物和其它碱性材料全部脱落或者溶解于良溶剂中。取出残余的器械，干燥称重，质量为M1。则，铁基基体在该观察时间点的的质量损失率为(M0-M1)/M0×100％。
当铁基基体在某个观察时间点的质量损失率W<5％时，认为铁基基体在植入时间点至该观察时间点的时间区域内未腐蚀。当铁基基体在某个观察时间点的质量损失率W≥90％时，认为铁基基体完全腐蚀，由植入时间点至该观察时间点之间的时间区域即为铁基基体的腐蚀周期。
7、降解后局部pH值
将骨科内固定植入医疗器械浸泡于PBS溶液(pH＝7.4±0.1)中，37℃腐蚀7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值。
实施例1
将纯铁铸成中空且表面有孔的钉状物，得到铁基体11；将纯镁粉、羟基磷灰石粉分散于熔融的聚左旋乳酸中，并将该混合物12填充于中空铁基体11中制得可吸收铁基骨钉，其横截面如图1所示。其中，聚左旋乳酸的重均分子量为1000kDa，镁元素与聚左旋乳酸的质量比为0.94。羟基磷灰石的质量为整个骨科内固定植入医疗器械的1％。
该骨钉初始弯曲强度为350MPa。将该骨钉植入动物体内，6个月后取出，铁降解10％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为7～8。
实施例2
将纯铁铸成中空且表面有孔的钉状物，得到铁基体；将氧化镁颗粒、羟基磷灰石粉分散于熔融的聚左旋乳酸中，并将该混合物填充于中空铁基体中制得可吸收铁基骨钉。其中，聚左旋乳酸的重均分子量为1000kDa，镁元素与聚左旋乳酸的质量比为0.008。羟基磷灰石的质量为整个骨科内固定植入医疗器械的1％。
该骨钉初始弯曲强度为350MPa。将该骨钉植入动物体内，6个月后取出，铁降解17％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为6～7。
实施例3
将纯铁铸成钉状，并通过离子渗氮增强其强度，得到钉状铁基体21；将块状锌合金、羟基磷灰石粉分散于熔融的聚消旋乳酸中，并将该混合物22涂敷于钉状铁基体21表面制得可吸收铁基骨钉，其横截面如图2所示。其中，聚消旋乳酸的重均分子量为500kDa，锌元素与聚消旋乳酸的质量比为1.3。羟基磷灰石的质量为整个骨科内固定植入医疗器械的3％。
该骨钉初始弯曲强度为450MPa。将该骨钉植入动物体内，6个月后取出，铁降解15％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨 科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为7～8。
实施例4
将纯铁铸成表面有凹槽的钉状，通过离子渗氮增强其强度，得到钉状铁基体；将氢氧化镁粉、羟基磷灰石粉分散于熔融的聚左旋乳酸中，并将该混合物涂敷于钉状铁基体的表面制得可吸收铁基骨钉。其中，聚左旋乳酸的重均分子量为500kDa，镁元素与聚左旋乳酸的质量比为0.014。羟基磷灰石的质量为整个骨科内固定植入医疗器械的3％。
该骨钉初始弯曲强度为420MPa。将该骨钉植入动物体内，6个月后取出，铁降解18％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为6～7。
实施例5
将低合金钢铸成中空的钉状31，该钉的内部还包括一个平行于铁钉的铁支撑杆32，其横截面如图3所示。用激光切割机将该铁钉切割成中空管腔结构。将氧化镁粉、羟基磷灰石粉分散于熔融的聚消旋乳酸中，并将该混合物33填充于铁基体内部得到可吸收铁基骨钉。其中，聚消旋乳酸的重均分子量为100kDa，镁元素与聚消旋乳酸的质量比为0.05。羟基磷灰石的质量为整个骨科内固定植入医疗器械的10％。
该骨钉初始弯曲强度为380MPa。将该骨钉植入动物体内，6个月后取出，铁降解25％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为6～7。
实施例6
将低合金钢铸成中空的表面有孔的棒状，得到棒状铁基体。将小锌棒、羟基磷灰石粉分散于熔融的聚消旋乳酸中，并将该混合物填充于铁棒内部得到可吸收铁基骨棒。其中，聚消旋乳酸的重均分子量为100kDa，锌元素与聚消旋乳酸的质量比为3。羟基磷灰石的质量为整个骨科内固定植入医疗器械的10％。
该骨棒初始弯曲强度为480MPa。将该骨钉植入动物体内，6个月后取出， 铁降解18％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为7～8。
实施例7
取一片纯铁片，用激光切割机将其切成网状，得到网状铁基体41。将氧化锌粉、羟基磷灰石粉分散于熔融的聚消旋乳酸中，并将该混合物42涂敷于该铁网表面及网孔中，得到铁基可吸收骨网，如图4所示。其中，聚消旋乳酸的重均分子量为5kDa，锌元素与聚消旋乳酸与的质量比为0.55。羟基磷灰石的质量为整个骨科内固定植入医疗器械的6％。
该骨网初始弯曲强度为350MPa。将该骨钉植入动物体内，6个月后取出，铁降解20％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为6～7。
实施例8
取一片纯铁片，用激光切割机将其切成网状，得到网状铁基体。将锌粉、羟基磷灰石粉分散于熔融的聚消旋乳酸中，并将该混合物涂敷于该铁网表面及网孔中，得到铁基可吸收骨网。其中，聚消旋乳酸的重均分子量为5kDa，锌元素与聚消旋乳酸的质量比为13.4。羟基磷灰石的质量为整个骨科内固定植入医疗器械的6％。
该骨网初始弯曲强度为500MPa。将该骨钉植入动物体内，6个月后取出，铁降解14％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为7～8。
实施例9
取中空表面有锌层的铁丝，编织获成铁网，得到网状铁基体51。将氧化锌粉、羟基磷灰石粉分散于熔融的聚消旋乳酸中，并将该混合物52涂敷于该铁网表面及网孔中，得到可吸收铁基骨网，如图5所示。其中，聚消旋乳酸的重均分子量为200kDa，锌元素与聚消旋乳酸的质量比为0.03。羟基磷灰石的质量为 整个骨科内固定植入医疗器械的7％。
该骨网初始弯曲强度为420MPa。将该骨钉植入动物体内，6个月后取出，铁降解27％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为6～7。
实施例10
将纯铁铸成中空且表面有孔的铁板61；将氧化镁粉、羟基磷灰石粉分散于熔融的聚消旋乳酸中，并将该混合物62填充于铁板61中间，得到可吸收铁基骨板，如图6所示。其中，聚消旋乳酸的重均分子量为200kDa，镁元素与聚消旋乳酸的质量比为2.1。羟基磷灰石的质量为整个骨科内固定植入医疗器械的7％。
该骨网初始弯曲强度为600MPa。将该骨钉植入动物体内，6个月后取出，铁降解20％。
将该骨科内固定植入医疗器械浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为7～8。
对比例1
聚左旋乳酸可吸收骨钉，聚左旋乳酸分子量为500kDa。
该骨钉初始弯曲强度为150MPa。
将可吸收骨钉浸泡于PBS溶液中，37℃水浴7天后，将骨科内固定植入医疗器械取出，立即用pH试纸检测器械表面pH值为4～5。
以上所述，仅为本发明较佳的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，可轻易想到的变化或替换，都应涵盖在本发明的保护范围之内。因此，本发明的保护范围应以权利要求的保护范围为准。

Claims (10)

  1. 一种骨科内固定植入医疗器械，其特征在于，包括铁基体和填充材料，所述填充材料包括聚乳酸和碱性物质，其中，所述聚乳酸的重均分子量为M WkDa，所述碱性物质包括金属元素，所述碱性物质中所述金属元素与所述聚乳酸的质量比为p，所述p与所述M W满足的公式为2M w^-0.8≤p≤30M w^-0.5。
  2. 如权利要求1所述的骨科内固定植入医疗器械，其特征在于，所述聚乳酸的重均分子量为5kDa～1000kDa。
  3. 如权利要求1所述的骨科内固定植入医疗器械，其特征在于，所述碱性物质选自镁、镁合金、锌、锌合金、氧化镁、氢氧化镁、氧化锌、氢氧化锌、碳酸镁、碳酸锌、磷酸镁、磷酸锌、碳酸钠、碳酸氢钠、氧化钙、氢氧化钙、碳酸钙、磷酸钙、羟基磷灰石中的一种或多种。
  4. 如权利要求1所述的骨科内固定植入医疗器械，其特征在于，所述碱性物质为镁、镁合金、锌、锌合金、氧化镁、氢氧化镁、氧化锌、氢氧化锌、碳酸镁、碳酸锌、磷酸镁、磷酸锌、碳酸钠、碳酸氢钠、氧化钙、氢氧化钙、碳酸钙、磷酸钙中的至少一种和羟基磷灰石的组合物。
  5. 如权利要求1所述的骨科内固定植入医疗器械，其特征在于，所述碱性物质为粉末状、颗粒状、块状或棒状中的一种或多种。
  6. 如权利要求4所述的骨科内固定植入医疗器械，其特征在于，所述羟基磷灰石的质量为所述骨科内固定医疗器械的质量的1～10％。
  7. 如权利要求1所述的骨科内固定植入医疗器械，其特征在于，所述聚乳酸为聚消旋乳酸或聚左旋乳酸。
  8. 如权利要求1所述的骨科内固定植入医疗器械，其特征在于，所述铁基体为中空结构，所述填充材料的填充于所述铁基体的内部；或者，所述铁基体为网状骨架结构，所述填充材料填充于所述网状骨架结构的网孔中；或者，所述铁基体为镂空空间骨架结构，所述填充材料填充于所述铁基体的镂空空间内部；或者，所述铁基体表面设有凹槽或孔洞，所述填充材料填充于所述铁基体的凹槽或孔洞中；或者，所述填充材料涂覆于所述铁基体表面。
  9. 如权利要求1所述的骨科内固定植入医疗器械，其特征在于，所述骨科内固定植入医疗器械为骨钉、骨板、骨棒或骨网。
  10. 如权利要求1所述的骨科内固定植入医疗器械，其特征在于，所述铁基体为纯铁、低合金钢或碳含量不高于2.5wt.％的铁基合金。
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