WO2024027650A1 - 一种骨水泥材料及其制备方法 - Google Patents

一种骨水泥材料及其制备方法 Download PDF

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WO2024027650A1
WO2024027650A1 PCT/CN2023/110243 CN2023110243W WO2024027650A1 WO 2024027650 A1 WO2024027650 A1 WO 2024027650A1 CN 2023110243 W CN2023110243 W CN 2023110243W WO 2024027650 A1 WO2024027650 A1 WO 2024027650A1
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starch
bone cement
less
phase
phosphate
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PCT/CN2023/110243
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French (fr)
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白艳洁
杨磊
张瑞
刘慧玲
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苏州大学
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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
    • 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
    • A61L27/20—Polysaccharides
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61L27/58—Materials at least partially resorbable by the body
    • 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
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/06—Flowable or injectable implant compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present application belongs to the field of biomedical materials, and particularly relates to a bone cement material and its preparation method.
  • Bone grafting can be achieved through autografts and allografts.
  • autologous transplantation has the problem that donors are limited and cannot properly meet the needs of the injured area, while allogeneic transplantation also has risks such as rejection reactions. Therefore, artificial bone repair materials have become the focus of research in the field of medical biomaterials.
  • bone cement as a bone repair material, has the advantages of in-situ solidification, simple operation, and can be directly filled into bone defects through injection, and has good application prospects.
  • Bone cement is an injectable bionic bone material.
  • common bone cements include polymethyl methacrylate bone cement (PMMA), calcium phosphate bone cement (CPC), etc.
  • the solid phase of polymethyl methacrylate bone cement is mainly PMMA copolymer powder, and the liquid phase is methyl methacrylate monomer. Solids are generated through polymerization reactions, which can have good injectability and high mechanical strength.
  • PMMA bone cement is a biologically inert material and cannot form an organic chemical interface with the host bone tissue.
  • shortcomings such as the heat generated during the solidification and polymerization process, the cytotoxic effect of the monomer, and the limited operability time also limit its clinical application.
  • Calcium phosphate bone cement (CPC), as a replacement product for polymethylmethacrylate bone cement, has been widely used in orthopedic treatment and correction since the 1980s.
  • Calcium phosphate bone cement is a bioactive inorganic material whose main components are different calcium phosphate salts. Under physiological conditions, it has self-curing properties. It has good injectability, can be arbitrarily plasticized, and isothermal in-situ curing.
  • existing calcium phosphate bone cement also has limitations. It has poor load-bearing, low strength, high brittleness, and is easy to collapse during the curing process in the body. .
  • this application proposes a bone cement, which includes a bone cement matrix phase, a reinforcing phase, and an amount of developer and solidifying liquid sufficient to achieve development.
  • the present application provides a method for preparing bone cement.
  • the preparation method includes: mixing a matrix phase, a reinforcing phase, an amount of developer sufficient to achieve development, and a solidifying liquid to form a bone cement slurry.
  • kits for preparing bone cement including a matrix phase, a reinforcing phase and an amount of developer sufficient to achieve development.
  • the kit further includes a liquid phase portion.
  • the liquid phase part includes a solidifying liquid that is at least capable of reacting with calcium phosphate salt in the matrix phase to form hydroxyapatite.
  • the matrix phase includes calcium phosphate salt; in one embodiment, the matrix phase includes selected from the group consisting of tricalcium phosphate, dicalcium phosphate dihydrate (DCDP), anhydrous calcium dibasic phosphate, and tetracalcium phosphate. , one or more of octacalcium phosphate, dicalcium phosphate, hydroxyapatite, and fluorapatite. In one embodiment, the matrix phase includes a mixture of both tricalcium phosphate and dicalcium phosphate dihydrate (DCDP).
  • DCDP tricalcium phosphate dicalcium phosphate dihydrate
  • the solidifying liquid is at least capable of reacting with calcium phosphate salt in the matrix phase to form hydroxyapatite.
  • the solidifying liquid includes selected from the group consisting of disodium hydrogen phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium hydrogen phosphate, dipotassium hydrogen phosphate, dilute phosphoric acid, calcium hydroxide, citric acid, glycerin and/or One or more of malonic acid.
  • the mass of the reinforcement phase is 1% to 100% of the mass of the matrix phase; in one embodiment, the mass of the reinforcement phase is 5% to 95% of the mass of the matrix phase; in one embodiment , the quality of the reinforcement phase is 10% to 50% of the quality of the matrix phase.
  • the developer is selected from the group consisting of barium-based developers, zirconium-based developers, bismuth-based developers, strontium-based developers, copper-based developers, aluminum-based developers, and/or combinations thereof.
  • the developer is selected from barium sulfate, zirconium oxide, bismuth subcarbonate, strontium carbonate, strontium halide, and/or combinations thereof.
  • the developer is selected from barium sulfate, zirconium oxide, and/or combinations thereof.
  • the reinforcing phase includes gelatinized starch.
  • the gelatinized starch is recovered by a method selected from the group consisting of alcohol precipitation, freeze drying and/or spray drying, or a combination thereof.
  • the gelatinized starch is recovered by freeze-drying.
  • the freeze-drying temperature is not higher than -10°C, or not higher than -20°C, or not higher than -30°C, or not higher than -40°C, or not higher than -50°C, Or not higher than -60°C, or not higher than -70°C, or not higher than -80°C, or not higher than -90°C, or not higher than -100°C.
  • the content of amylose in the gelatinized starch is lower than 90%, lower than 80%, lower than 70%, lower than 60%, lower than 50%, lower than 40%, low Below 30%, below 20%, below 10%, or below 5%, or below 3%.
  • the starch includes one or more selected from the group consisting of ordinary corn starch, waxy corn starch, high amylose corn starch, tapioca starch and potato starch. In one embodiment, the starch includes waxy cornstarch and/or regular cornstarch.
  • the viscosity of the gelatinized starch is less than 10 4 at 0.1 rad/s and less than 10 3 at 10 rad/s. In one embodiment, the viscosity of the gelatinized starch is less than 10 3 at 0.1 rad/s and less than 10 2 at 10 rad/s. In one embodiment, the starch swelling degree after gelatinization is greater than 20%. In one embodiment, the gelatinized starch shows only one broad peak with a diffuse and smooth shape in the XRD diffraction pattern.
  • the starch scanning electron microscopy image shows irregular flakes; in one embodiment, the starch scanning electron microscopy image is basically as shown in D6 or D7 in Figure 3-2.
  • the bone cement has a compressive strength greater than 20MPa; in one embodiment, the bone cement has a compressive strength greater than 30MPa; in one embodiment, the bone cement has a compressive strength greater than 40MPa ; In one embodiment, the bone cement has a compressive strength greater than 50MPa; In one embodiment, the bone cement has a compressive strength greater than 60MPa.
  • the scanning electron microscope image of the cross-section of the bone cement shows that there is no aggregation of needle-like structures; in one embodiment, the scanning electron microscope image of the cross-section of the bone cement is basically as shown in G6 in Figure 9-4; In one embodiment, the cross-section of the bone cement is basically as shown in G7 in Figure 9-4.
  • the bone cement has an initial setting time of 5min to 30min and a final setting time of 10min to 40min; in one embodiment, the bone cement has an initial setting time of 15min to 30min and a final setting time of 20min to 40min; In one embodiment, the bone cement has an initial setting time of 20 to 30 minutes and a final setting time of 25 to 40 minutes; in one embodiment, the bone cement has an initial setting time of 25 to 30 minutes and a final setting time of 35 to 40 minutes.
  • This application also provides the use of a starch material for preparing the above-mentioned bone cement.
  • the starch material includes gelatinized starch.
  • the bone cement of the present application has good operability, is easy to inject, is not easy to collapse, has good mechanical properties, and can be well matched with autogenous bone.
  • the bone cement of the present application has high mechanical strength and can be used for load-bearing structural bone parts.
  • Figure 1 is a bar graph showing the strength of composite bone cement with added starch reinforcement phase.
  • Figure 2 shows the viscosity results of modified starch.
  • Figures 3, 4 and 5 are the scanning electron microscopy, XRD and infrared spectra of starch respectively.
  • Figure 6 is a photo of the results of bone cement injectability and collapse resistance.
  • Figure 7 shows the viscosity results of composite bone cement.
  • Figure 8 shows the XRD pattern of bone cement.
  • Figure 9 is a scanning electron microscope image of bone cement.
  • Figure 10 shows the infrared spectrum of bone cement.
  • the matrix phase is the component that makes up the bulk of the bone cement.
  • the matrix phase contains one or more calcium phosphate salt powders, for example, selected from the group consisting of tricalcium phosphate (alpha type or beta type), calcium hydrogen phosphate dihydrate, anhydrous calcium hydrogen phosphate, tetracalcium phosphate, One or more of octacalcium phosphate, dicalcium phosphate, hydroxyapatite, and fluorapatite.
  • the matrix phase in the powder state may include acidic calcium phosphate salt powder and alkaline calcium phosphate salt powder.
  • one or more calcium phosphate salt powders in the matrix phase in the powder state undergo a series of hydration reactions to finally form hydroxyapatite (HA) that is crystallized to a certain extent.
  • hydroxyapatite (HA) crystals may also be added to the matrix phase. The added hydroxyapatite (HA) crystals can help the hydration process of the matrix phase, reduce the setting time, and make the bone cement matrix phase more prone to self-setting.
  • the matrix phase in the powder state includes tricalcium phosphate.
  • Tricalcium phosphate mainly has three crystal forms: low-temperature phase ⁇ -TCP and high-temperature phase ⁇ -TCP, ⁇ ’-TCP. Among them, the ⁇ -TCP crystal form can be stabilized at room temperature through rapid cooling.
  • the matrix phase in the powder state includes a mixture of alpha-tricalcium phosphate (alpha-TCP) and dicalcium phosphate dihydrate (DCDP).
  • tetracalcium phosphate may also be added to the matrix phase including ⁇ -tricalcium phosphate ( ⁇ -TCP) and dicalcium phosphate dihydrate (DCDP).
  • the matrix phase contains at least two calcium phosphate salt powders, and the different calcium phosphate salt powders are mixed by a dry method.
  • the dry mixing includes a ball milling step.
  • the different calcium phosphate salt powders and agate balls are dry-mixed according to a certain ball-to-material ratio, for example, the ball-to-material ratio is 1:2.
  • the ball-milled mixed calcium phosphate salt is screened to control the particle size level of the matrix phase powder to ensure that the matrix phase particles and the liquid phase can be quickly and fully dissolved to promote the hydration reaction.
  • the calcium phosphate salt in the matrix phase can be made from carbonated apatite.
  • carbonate apatite synthesized in solution is heated for several hours, and the resulting solid is ground to obtain matrix phase powder whose main components are sodium calcium phosphate, tetracalcium phosphate, and tricalcium phosphate.
  • the ⁇ -tricalcium phosphate powder in the calcium phosphate salt powder in the matrix phase is obtained by calcining at high temperature and then quenching.
  • ⁇ -tricalcium phosphate can be obtained by first maintaining it at high temperature for 4 hours and then rapidly cooling it.
  • compounds in addition to calcium phosphate salts, can be added to the matrix phase to supplement trace elements zinc, magnesium, strontium and/or fluorine in the human body to optimize the osteogenic properties of the bone cement.
  • a "reinforcing phase” is an added ingredient, such as starch, that optimizes the properties of bone cement.
  • the starch includes one or more selected from the group consisting of ordinary corn starch, waxy corn starch, high amylose corn starch, tapioca starch and/or potato starch.
  • the starch can be physically or chemically modified, for example, through gelatinization, molecular cross-linking, cationic modification, calcium ion modification, reducing molecular chain length, increasing branching, increasing One or more of the treatments for cross-linking.
  • the reinforcing phase is gelatinized starch.
  • the gelatinized starch can be recovered by precipitation with an alcohol solution (also known as “alcohol precipitation”), spray drying, and/or freeze-drying (also known as “freeze precipitation”). "dry”) for recycling.
  • Alcohol precipitation also known as "alcohol precipitation”
  • freeze-drying also known as “freeze precipitation”
  • dry for recycling.
  • Gelatinization can destroy the original crystal structure of starch, eliminate the original spherical particle state of starch, and form an amorphous and irregular state.
  • Starch has been modified by gelatinization and can be dissolved at room temperature. It can be evenly mixed with other components of bone cement to form a solidified three-dimensional network.
  • the recycling treatment method should keep the amorphous and irregular state as much as possible to obtain, for example, irregular blocks and/or flakes.
  • the recovery treatment method of starch after gelatinization modification should avoid the generation of microcrystalline structure as much as possible, reduce the number of crystals, and improve the swelling ability of starch at room temperature.
  • the gelatinized starch that is, the starch recovered through gelatinization modification, can achieve one or more of the following: having a lower amylose content, improving the starch swelling ability, and reducing the expansion of the starch. Add the viscosity developed in the liquid phase. The above treatment of starch helps to improve the physical and chemical properties of bone cement.
  • the starch of the reinforcing phase may be starch recovered through an alcohol precipitation method.
  • the starch recovered through the alcohol precipitation method can be prepared by mixing the starch with water or an aqueous liquid to gelatinize the starch to form gelatinized starch. Cool the gelatinized starch. After cooling to room temperature, add absolute ethanol to the cooled starch, let it stand at room temperature for a period of time, remove the supernatant after layering, and then add absolute ethanol to the precipitate. , then let it stand, and after filtering, drying, crushing and sieving, the starch recovered through the alcohol precipitation method is obtained.
  • the starch of the reinforcing phase can also be starch recovered through a freeze-drying method.
  • the starch recovered by the freeze-drying method can be prepared by dissolving the starch in water or an aqueous liquid under stirring and heating conditions to gelatinize the starch, and form gelatinized starch after a certain period of time, and then After the gelatinized starch is cooled to room temperature, it is freeze-dried in a freeze-drying equipment, and then crushed and sieved to obtain the starch recovered by the freeze-drying method.
  • the reinforcing phase can also be starch recovered by spray drying methods.
  • the starch recovered by the spray drying method can be prepared by dissolving the starch in water or an aqueous liquid under stirring and heating conditions to gelatinize the starch. After a certain period of time, gelatinized starch is formed, and the paste is After the starch is cooled to room temperature, it is sent to the spray drying equipment. After spray drying in the spray drying equipment, it is then crushed and sieved to obtain the starch recovered by the spray drying method.
  • the reinforcing phase can be selected from waxy corn starch and ordinary corn starch with lower amylose content, and the waxy corn starch and ordinary corn starch are gelatinized and modified and recovered through freeze-drying.
  • the reinforcing phase has a higher amylopectin content and a higher degree of swelling.
  • the apparent morphology of the starch under a scanning electron microscope shows a loose structure, flake-like, a large contact area, and no obvious crystallization.
  • the X-ray diffraction pattern shows that there are no obvious sharp peaks, showing diffuse and smooth broad peaks, and is dissolved in the liquid phase to form a lower viscosity.
  • a "developer” is an ingredient that imparts developing properties to bone cement, for example, barium sulfate, zirconium oxide, and/or combinations thereof. In some embodiments, adding a developer sufficient to achieve development allows the bone cement to be developed, which can meet the intraoperative development requirements.
  • a "curing liquid” is a liquid phase used to mix with the matrix phase, developer and/or reinforcing phase in the powdered state to form a bone cement slurry.
  • Bone cement slurry system Pasty bone cement.
  • Common solidifying liquids include one selected from disodium hydrogen phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium hydrogen phosphate, dipotassium hydrogen phosphate, dilute phosphoric acid, calcium hydroxide, citric acid, glycerin and/or malonic acid. or more.
  • the solidified liquid may be in the form of a liquid such as a solution, or in the form of a solid that is prepared to form a liquid.
  • the solidification liquid can also be physiological saline, serum and/or blood, etc.
  • the bone cement slurry eventually forms a solid solid after self-curing, that is, solid bone cement is obtained.
  • the matrix phase undergoes a hydration reaction with the water in the solidifying solution.
  • ⁇ -TCP ⁇ -tricalcium phosphate
  • DCDP calcium dibasic phosphate dihydrate
  • ordinary calcium phosphate bone cement refers to calcium phosphate bone cement that contains only a matrix phase and does not contain a reinforcing phase and a developer.
  • developed calcium phosphate bone cement refers to a calcium phosphate bone cement that contains a matrix phase but does not contain a reinforcing phase in addition to the matrix phase and contains a developer.
  • composite bone cement refers to bone cement containing a matrix phase and, in addition to the matrix phase, a reinforcing phase and a developer.
  • ⁇ -TCP dicalcium phosphate dihydrate
  • DCPD dicalcium phosphate dihydrate
  • Collapse resistance test Encapsulate the bone cement slurry into a 1mL syringe, and then inject it directly into a petri dish filled with deionized water at 37°C. Place the petri dish on a vibrating device (purchased from Scilogex USA, model SK-O330-Pro), and set Vibrate at a speed of 180r/min and maintain it for 1 minute, then let it stand for 24 hours in deionized water at 37°C. If the bone cement does not break, it indicates that it has good anti-collapse properties. Observe whether collapse occurs and take photos. The bone cement results in this example are shown in Figure 6-1. The results show that the control calcium phosphate bone cement has poor disintegration resistance.
  • Curing time test The testing of curing time is carried out according to ASTM C191-03 standard method. Fill the cement paste into a stainless steel mold (diameter 6 mm, height 12 mm) and flatten it with a spatula. The initial setting needle (weight 113.4g, diameter 2.12mm) and final setting needle (weight 453.6g, diameter 1.06mm) of the Vicat instrument were used to measure the initial setting time and final setting time of bone cement respectively. Each sample was tested five times. , the results are expressed as mean ⁇ standard deviation. In this example, the bone cement curing time was 3.3 ⁇ 0.5min, and the final setting time was 9.0 ⁇ 0.4min.
  • the obtained bone cement slurry was filled into a cylindrical mold with a diameter of 6 mm and a height of 12 mm. After solidification, the cement sample in the mold was taken out and the cylindrical sample was stored at 37°C and >60% RH for 3 days. Then break the cylindrical sample to expose the cross section, take the sample and stick it on the double-sided conductive adhesive with the cross section of the sample facing up. Place the sample in an ion sputtering instrument and spray gold for 60 seconds, coat the sample with a conductive film, then send the sample tray into the scanning electron microscope sample chamber, adjust the position of the sample stage, set the voltage to 15kV, and start scanning and taking pictures.
  • the SEM results of bone cement in this example are shown in Figure 9-1.
  • developed calcium phosphate bone cement was prepared according to the following method: the matrix phase powder was prepared according to the method in comparative example 1. Grind the barium sulfate powder (BaSO 4 ) and pass it through a 200-mesh sieve. Add a certain amount of barium sulfate powder to the matrix phase powder and grind for 2 minutes. Add the obtained mixed powder to the disodium hydrogen phosphate solution and mix evenly to obtain a developed calcium phosphate bone cement slurry with barium sulfate as a developer.
  • the matrix phase powder was prepared according to the method in comparative example 1. Grind the barium sulfate powder (BaSO 4 ) and pass it through a 200-mesh sieve. Add a certain amount of barium sulfate powder to the matrix phase powder and grind for 2 minutes. Add the obtained mixed powder to the disodium hydrogen phosphate solution and mix evenly to obtain a developed calcium phosphate bone cement slurry with barium sulfate as a developer.
  • Porosity Inject bone cement slurry into a stainless steel mold (diameter 6 mm, height 12 mm). After solidification, take out the cement sample from the mold. Store the sample at 37°C and >60RH% for 3 days. At 150 Dry in an oven at °C for 5 hours. Place the dried sample into a dilatometer and keep it horizontal. Perform low-pressure analysis first. During low-pressure analysis, first use a mercury porosimeter to evacuate the sample until the absolute pressure reaches less than 50 ⁇ m Hg (0.0067kPa), then continue to evacuate for 5 minutes, fill the mercury into the dilatometer through the siphon method, and then introduce nitrogen to maintain the pressure to 0.5psi (3.4kPa).
  • Density Inject the bone cement slurry into the stainless steel mold (diameter 6 mm, height 12 mm), and take out the sample after solidification. Store the sample at 37°C with saturated humidity for 3 days. Take out the sample and weigh it. The mass is m 1 . Then, pour the water into the beaker of the density balance (Shanghai Yueping, model FA2104J), and hang the hanging basket in the water to ensure that there are no air bubbles. Put the sample into the hanging basket and weigh the weight of the sample in water as m 2 .
  • the density of bone cement samples can be calculated as follows:
  • ⁇ represents the density of bone cement (g/cm 3 )
  • ⁇ H 2 O represents the density of water (g/cm 3 )
  • ⁇ air represents the density of air (g/cm3)
  • m 1 represents the mass of bone cement in the air ( g)
  • m 2 represents the mass of bone cement in water (g).
  • the matrix phase powder was prepared according to the method in Comparative Example 1; barium sulfate powder was ground and passed through a 200-mesh sieve as the developer; pregelatinized starch (purchased from Henan Jianjie Starch Products Co., Ltd.) was used as the reinforcing phase.
  • the obtained mixed powder is ground and then mixed with disodium hydrogen phosphate solution to obtain a composite bone cement slurry.
  • the mechanical properties of the obtained bone cement samples were analyzed. The results are shown in Figure 1.
  • the ordinate "Compressive Strength” represents the compressive strength; the abscissa represents the mass ratio of the matrix phase and the reinforcement phase. For example, 12:1 represents the reinforcement phase. The mass is 1/12 of the mass of the matrix phase.
  • Example 2 Composite bone cement with different types of developers
  • Matrix phase powder was prepared according to the method in Comparative Example 1; barium sulfate powder was ground and passed through a 200 mesh sieve as developer 1; zirconium oxide developer powder was ground and passed through a 200 mesh sieve as developer 2; pregelatinized starch (purchased) from Henan Jianjie Starch Products Co., Ltd.) as reinforcing phase.
  • the mass ratio of matrix phase to reinforcement phase is 3:1.
  • the obtained mixed powder is ground and then mixed with a disodium hydrogen phosphate solution to obtain a composite bone cement slurry using developer 2.
  • the compressive strength of the obtained bone cement slurry was measured according to the method of Example 1, and the result was 57.7 ⁇ 4.0MPa.
  • Waxy corn starch (Qinhuangdao Lihua Co., Ltd.), ordinary corn starch (Qinhuangdao Lihua Co., Ltd.), high amylose corn starch (Shanghai Bicai Co., Ltd.), cassava starch (Tongchun Starch Processing Factory) and potato starch (Inner Mongolia Huazhou) were selected. Ou Starch Industrial Co., Ltd.), carried out the following modification treatment.
  • Method 1 Add 10g of starch and 490mL of deionized water into a 1000mL beaker, stir and heat in a boiling water bath for 30 minutes. After cooling to room temperature, add 1500 mL of absolute ethanol to the starch solution and let it stand at room temperature for 1 hour. After standing for layering, pour out the supernatant, add 500 ml of absolute ethanol to the precipitate, let stand for another hour, and obtain a filter cake after suction filtration. Crush the filter cake and place it in an oven at 40-45°C to dry overnight. Crush the dried sample and pass it through a 100-mesh sieve to obtain the modified starch treated in method 1.
  • Method 2 Weigh a certain mass of starch, add deionized water, prepare a starch slurry with a mass fraction of 5%, heat in a boiling water bath and stir for 30 minutes. After the starch slurry is cooled to room temperature, it is frozen and processed by a freeze dryer. After the freeze-drying is completed, the starch is taken out, crushed and sieved to obtain the modified starch treated in method 2.
  • the waxy corn starch, ordinary corn starch, high amylose corn starch, cassava starch and potato starch treated by method 1 are numbered D1-D5 respectively; the waxy corn starch, ordinary corn starch, high amylose corn starch, cassava starch and treated by method 2
  • Potato starch is numbered D6-D10 respectively; untreated waxy corn starch, ordinary corn starch, high amylose corn starch, tapioca starch and potato starch are numbered D11-D15 respectively.
  • waxy cornstarch has the lowest amylose content.
  • the ordinary corn starch treated by method 2 achieved a significantly lower amylose content.
  • a rheometer purchased from TA Instruments, model AR2000 to measure the viscosity of the different starches mentioned above (corresponding to the starches numbered D1-D10 in Example 3).
  • Frequency scanning is used during measurement, and the angular frequency scanning interval is set to 0.1-10rad. /s, the strain amplitude is 1%, and the changes in material properties are observed at 25°C.
  • the apparent morphology of starch was characterized by scanning electron microscopy (SEM) ( Figure 3). The results showed that ungelatinized starch was in the form of spherical particles with a smooth surface ( Figure 3-3).
  • the modified starch processed by method 1 is in the shape of irregular granules ( Figure 3-1, in which the marks D1-D5 in the upper left corner correspond to the starch numbers D1-D5 respectively).
  • the modified starch processed by method 2 is in the form of lamellae ( Figure 3-2, where the marks D6-D10 in the upper left corner correspond to the starch numbers D6-D10 respectively). Starch is gelatinized, destroying the original structure of starch granules.
  • the crystalline areas in starch granules change from a tightly arranged state to a loose state, and continue to absorb water and swell, forming an irreversible phase change. After swelling to a certain extent, the granules rupture, destroying the original granule shape and turning into a disordered gel state. After drying It can take on irregular shapes after recycling.
  • the branches of amylose and amylopectin molecules tend to be arranged in parallel again and move closer to each other. They are combined with each other through hydrogen bonds and then reorganized into mixed microcrystals, so it is easy to show irregular shapes in the end. blocky, with a relatively dense structure.
  • the starch recovered in method 2 has a looser structure in comparison, especially the starches numbered D6 and D7.
  • the apparent morphology under the electron microscope shows irregular flakes, because the starch recovered in method 2 has a looser structure.
  • the drying temperature dropped rapidly during the process, limiting the movement of starch chains, which gave the starch obtained by method 2 a loose and porous morphology.
  • the recycling process in method 2 can better restrict the movement of starch chains, making the starch chains less connected, making the starch quickly cross the aging temperature, and well avoiding the "retrogradation" of starch, so that a starch with a looser structure can be obtained. sample.
  • Example 3 Perform functional group analysis on the starches numbered D1-D15 in Example 3 using an infrared spectrometer (purchased from Thermo Fisher, USA, model Nicolet TM iS20). The specific method is as follows: take 1 to 2 mg of completely dried starch and place it in a spectral analysis instrument. Test area. Set the scanning range to 500 ⁇ 4000cm -1 and the resolution to 0.25cm -1 for testing. The results obtained are shown in Figure 5.
  • Figure 5-1 shows the starch processed by method 1, corresponding to the starch numbers D1-D5 respectively;
  • Figure 5-2 shows the starch processed by method 2, corresponding to the starch numbers D6-D10 respectively;
  • Figure 5-3 shows the starch without pasting
  • the converted raw starches correspond to starch numbers D11-D15 respectively.
  • the asymmetric stretching vibration peak of the CH bond in CH 2 is in the range of 2850 to 2900 cm -1 , while the stretching vibration absorption band of the hydroxyl group appears in the range of 3000 to 3600 cm -1 , which constitutes the Overall structure, this region is mainly generated by the stretching vibration of intramolecular, intermolecular and free intermolecular hydroxyl groups.
  • the stretching vibration peaks of CC and CO are at 1145cm -1 , and the bending vibration peak of COC is at 995cm -1 .
  • Example 4 Preparation of composite bone cement using different modified starch as reinforcing phase and its characterization
  • Matrix phase powder was prepared by referring to the method in Comparative Example 1; barium sulfate powder was ground and passed through a 200-mesh sieve as a developer; the aforementioned starches numbered D1 to D10 were used as reinforcing phases to prepare bone cement according to the method described below.
  • the obtained bone cement sample number They correspond to G1 ⁇ G10 respectively.
  • the mass ratio of matrix phase to reinforcement phase is 3:1.
  • the obtained mixed powder was ground for 2 minutes, and then mixed with disodium hydrogen phosphate solution to obtain a composite bone cement slurry.
  • the obtained bone cement slurry is further solidified to form solid bone cement.
  • the viscosity of bone cement was measured using a rheometer (purchased from TA Instruments, model AR2000).
  • a uniform bone cement paste is obtained.
  • the reinforcing phases were respectively used as starch samples D1-D5 of Example 3, and the corresponding numbers of the obtained bone cement slurries were J1-J5.
  • composite bone cement also exhibits shear thinning properties.
  • the viscosity trend of composite bone cement is consistent with the viscosity of the reinforcing phase starch. That is, by using starch with lower viscosity as the reinforcing phase, the viscosity of the composite bone cement can be reduced, and accordingly the composite bone cement achieves higher mechanical strength. Lower starch viscosity can affect the even distribution of starch in bone cement, thereby affecting the flow and mechanical properties of bone cement.
  • the bone cement powder has a characteristic peak of ⁇ -TCP located at a 2 ⁇ diffraction angle of 31°.
  • the characteristic peaks of ⁇ -TCP gradually disappear after the hydration reaction of the calcium phosphate salt in the composite bone cement, while the characteristic peaks of hydroxyapatite at 2 ⁇ diffraction angles of 32°, 47° and 49° gradually increase with time, and the characteristic peaks of ⁇ -TCP The peak began to decrease after 3 hours and disappeared after 1 day.
  • the characteristic peaks of BaSO4 remain constant during the solidification process. The addition of starch reinforcing phase and BaSO 4 will not affect the formation of hydroxyapatite, the final product of the hydration reaction of calcium phosphate bone cement.
  • the functional groups of ordinary calcium phosphate bone cement and composite bone cement were characterized by an infrared spectrometer (purchased from Thermo Fisher, USA, model Nicolet TM iS20).
  • the method is as follows: Inject the bone cement slurry into a cylindrical stainless steel mold with a diameter of 6 mm and a height of 12 mm. , then push the sample out of the mold and store it at 37°C with saturated humidity for 3 days until it fully reacts and solidifies. Grind the sample with a mortar, take a small amount of powder sample and place it in the test area of the spectrometer. Set the scanning range to 500 to 4000cm -1 and the resolution to 0.25cm -1 to conduct the test.
  • the infrared spectrum of the composite bone cement is shown in Figure 10;
  • Figure 10-1 is the infrared spectrum of the composite bone cement with starch treated by method 1 as the reinforcing phase;
  • Figure 10-2 is the starch treated with method 2 as the reinforcing phase.
  • the infrared spectrum of composite bone cement and the infrared spectrum of ordinary calcium phosphate bone cement. in, G1-G10 respectively correspond to the corresponding numbered composite bone cement, and CPC stands for ordinary calcium phosphate bone cement.
  • the characteristic peaks of organic groups unique to starch are also covered by the characteristic peaks of calcium phosphate and hydroxyapatite. It can be seen that the starch-reinforced phase in composite bone cement does not interfere with the chemical composition of the matrix phase, does not participate in chemical reactions, and does not generate new groups.
  • both the developed calcium phosphate bone cement and the composite bone cement have improved mechanical strength, but the mechanical strength of the composite bone cement has been significantly improved.
  • a mechanical strength of 30MPa can be achieved. This strength level makes it possible for bone cement to be used in bone structures in load-bearing parts.
  • partially reinforced phase starch for example, modified waxy corn starch and modified ordinary corn starch recovered by freeze-drying
  • the strength of composite bone cement can be increased to more than 50 MPa. This level of strength not only allows composite bone cement to be used in load-bearing bone structures, but also achieves good safety.
  • Composite bone cement with modified starch can also improve the curing time.
  • the initial setting time of ordinary calcium phosphate bone cement is less than 5 minutes, and the final setting time is less than 10 minutes.
  • Add ungelatinized starch the initial setting time is approximately 10 minutes, and the final setting time is approximately 15 minutes.
  • the results in the above examples show that adding gelatinized starch can more effectively improve the curing time, for example, improving the initial setting time to close to 15min or even slightly higher than 25min, while improving the final setting time to higher than 20min or even slightly higher. This curing time of 35 minutes makes bone cement more suitable for surgical operations.
  • the curing time is usually required to reach about 15 minutes; more preferably, the curing time can be further optimized, such as reaching about 30 minutes, in order to obtain sufficient operating time. Sufficient operating time can achieve good injection and filling of bone cement. If the curing time is too short, when the bone cement is injected into the bone structure, the bone cement will solidify prematurely, which will result in the slurry not being fully injected and evenly and fully filled.
  • Composite bone cement with modified starch can also improve injectability and disintegration resistance.
  • the injectability results show that the injectability results of ordinary calcium phosphate bone cement are less than 90%, while the composite bone cement containing modified starch reinforced phase has achieved excellent injectability, and the injectability results are all greater than 90%.
  • modified starch as a reinforcing phase, can significantly improve the collapse resistance of bone cement. It maintained its integrity under the test conditions and did not collapse. In summary, it can be seen that modified starch can enable composite bone cement to achieve both excellent injectability and collapse resistance.
  • the bone cement performance results in Example 4 combined with the starch property results in Example 3 show that the properties of starch significantly affect the performance parameters of bone water.
  • the parameters of the composite bone cement can be adjusted, so that the bone cement can achieve higher mechanical strength, a more suitable curing time, and at the same time be easy to inject and not easy to collapse.
  • waxy corn starch especially waxy corn starch recovered by freeze-drying, shows higher mechanical strength when used as a reinforcing phase, and at the same time shows a more suitable curing time, is easy to inject, and is not easy to collapse.
  • ordinary corn starch, after freeze-drying recovery shows better flow properties than alcohol precipitation recovery, which can make bone cement easier to inject and less likely to collapse.
  • the curing time of bone cement has also been improved. Optimized, more conducive to surgical operations, and the mechanical strength of bone cement is higher. Through gelatinization, especially when recycled through freeze-drying methods, the characteristics of the reinforced phase starch and the characteristics of bone cement can be improved, allowing the bone cement to achieve better performance in terms of curing time, mechanical strength, injectability and collapse resistance.
  • the scanning electron microscopy results of the starch in the aforementioned examples show that the modification and recovery methods significantly affect the apparent morphology of the starch. Recovered through freeze-drying method, the apparent morphology of waxy corn starch and ordinary corn starch under the electron microscope is irregular flakes.
  • the starch structure is loose and porous, which can form better contact with water and easily dissolve to form a gel. , showing good swelling capacity at room temperature and low starch viscosity, it can also achieve good fluidity when used in bone cement, obtain relatively uniform bone cement, achieve excellent mechanical strength, and have good Operability.
  • starch that has been recycled through freeze-drying can better maintain the state in which the crystallization area has been completely destroyed.
  • starch recovered by freeze-drying can improve the curing time of bone cement and improve the mechanical strength to a greater extent.
  • the microscopic surface morphology of ordinary calcium phosphate bone cement and developed calcium phosphate bone cement has more obvious needle-like structures.
  • the obvious needle-like structure is a typical hydroxyapatite crystal morphology.
  • the composite bone cement containing starch-reinforced phase the same needle-shaped crystal particles can also be observed, indicating that the hydration products of CPC do not change significantly after the addition of modified starch.
  • ordinary calcium phosphate bone cement and developed calcium phosphate bone cement have obvious clusters of needle-like structures, while the composite bone cement containing starch-reinforced phase shows smaller needle-like structures and pores. It is also smaller.
  • the surface morphology structure in the scanning electron microscope picture shows more uniformity and less acicular crystal structure aggregation.
  • bone cement can achieve higher mechanical strength, relatively better curing time, and operational performance. Better.
  • waxy cornstarch and ordinary cornstarch are used as reinforcing phases, the surface morphology is more uniform and the pores are smaller than other samples.
  • the compressive strength of composite bone cement can be increased by more than 4 times compared to ordinary calcium phosphate bone cement, reaching 50-60MPa, which fully meets the mechanical requirements of load-bearing bones and has both Good injectability and disintegration resistance.
  • the composite calcium phosphate bone cement of the present application has shown good results in terms of degradability and other aspects. Compared with currently existing bone cements, it shows advantages in major properties such as strength, curing time, degradability, injectability and collapse resistance, and can achieve good comprehensive effects.
  • the terms “includes,” “includes,” “has,” “can,” “contains,” and variations thereof are intended to be open-ended linking phrases, terms or words that do not exclude the possibility of additional operations or structures.
  • the singular forms “a”, “an” and “the” include plural referents unless the context clearly dictates otherwise.
  • the present disclosure also contemplates other embodiments “comprising”, “consisting of embodiments or elements set forth herein”, and “consisting essentially of embodiments or elements set forth herein”, regardless of Whether it is clearly stated.
  • the conjunctive term "or" includes any and all combinations of one or more of the listed elements with which the conjunctive term is associated.
  • a device comprising A or B may refer to a device that includes A but in which B is not present, a device that includes B but in which A is not present, or a device in which both A and B are present.
  • the phrase "at least one of A, B, ... and N" or "at least one of A, B, ... N or a combination thereof” is defined in the broadest sense to mean selected from the group consisting of A, B, ...and one or more elements of N, that is, Any combination of one or more of elements A, B, ... or N, including any one element alone, or in combination with one or more of the other elements mentioned, which may also include combinations not listed additional elements.

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Abstract

一种含有淀粉成分的骨水泥材料及其制备方法。所述骨水泥具有更高的力学强度、更适宜手术操作的固化时间。注射性和抗溃散性良好，操作性能优良，同时兼有良好的降解性能等，综合性能优异。还涉及一种制备所述骨水泥的试剂盒。

Description

一种骨水泥材料及其制备方法 技术领域
本申请属于生物医用材料领域，特别地涉及一种骨水泥材料及其制备方法。
背景技术
骨质疏松等疾病或者意外伤害等都可能导致人体骨结构的损伤。虽然，人体的骨骼结构本身具备一定的修复能力，在损伤较小时可以自行愈合，但当存在较大损伤时，则需要骨体移植。目前，全球约有数百万骨损伤患者需要骨移植等手术治疗。骨移植可以通过自体移植和异体移植实现。但自体移植存在供体有限，不能良好满足损伤处的需求的问题，而异体移植又存在排异反应等风险。于是，人工骨修复材料成为了医用生物材料领域的研究重点。其中，骨水泥作为一种骨修复材料具有原位固化、操作简单，可以通过注射直接填充到骨缺损部位等优点，具有良好的应用前景。
骨水泥系可注射仿生骨材料。目前，常见的骨水泥有聚甲基丙烯酸甲酯骨水泥(PMMA)、磷酸钙骨水泥(CPC)等。聚甲基丙烯酸甲酯骨水泥的固相主要是PMMA共聚物粉末，液相是甲基丙烯酸甲酯单体，通过聚合反应生成固体，其可以具有良好的可注射性，力学强度高。目前，经皮椎体成型术治疗骨质疏松性椎体压缩骨折时，使用的医用骨水泥一般是不可降解的聚甲基丙烯酸甲酯材料。PMMA骨水泥属于生物惰性材料，不能与宿主骨组织形成有机的化学界面结合，另外凝固聚合过程中产生热量、单体的细胞毒性作用、可操作时间有限等不足也限制了其临床应用。
磷酸钙骨水泥(CPC)作为聚甲基丙烯酸甲酯骨水泥的替换产品，自1980年代以来，被广泛应用于骨科的治疗和矫正。磷酸钙骨水泥是生物活性无机材料，其主要成分是不同的磷酸钙盐。在生理条件下，具有自固化特性等。其具有良好的可注射性，可任意塑性，等温原位固化等特性，但是，现有的磷酸钙骨水泥也存在局限，其承重差，强度低，脆性大，在体内固化过程中，容易溃散。
发明内容
针对现有技术中存在的技术问题，本申请提出了一种骨水泥，所述骨水泥基体相、增强相、足以实现显影的量的显影剂与固化液。
本申请提供了一种骨水泥的制备方法，所述制备方法包括：将基体相、增强相、足以实现显影的量的显影剂与固化液混合形成骨水泥浆体。
本申请提供了一种用于制备骨水泥的试剂盒，包括基体相、增强相和足以实现显影的量的显影剂。在一个实施方式中，所述试剂盒还包括液相部分。在一个实施方式中，所述液相部分包括固化液，所述固化液至少能够与所述基体相中的磷酸钙盐反应形成羟基磷灰石。
在一个实施方式中，所述基体相包括磷酸钙盐；在一个实施方式中，所述基体相包括选自磷酸三钙、二水合磷酸氢钙(DCDP)、无水磷酸氢钙、磷酸四钙、磷酸八钙、磷酸二氢钙、羟基磷灰石、氟磷灰石中的一者或多者。在一个实施方式中，所述基体相包括磷酸三钙和二水合磷酸氢钙二者(DCDP)混合物。
在一个实施方式中，所述固化液至少能够与所述基体相中的磷酸钙盐反应形成羟基磷灰石。在一个实施方式中，所述固化液包括选自磷酸氢二钠、磷酸氢钠、磷酸二氢钠、磷酸氢钾、磷酸氢二钾、稀磷酸、氢氧化钙、柠檬酸、甘油和/或丙二酸中的一者或多者。
在一个实施方式中，所述增强相质量为基体相质量的1％～100％；在一个实施方式中，所述增强相的质量为基体相质量的5％～95％；在一个实施方式中，所述增强相质量为基体相质量的10％～50％。
在一个实施方式中，所述显影剂选自钡基显影剂、锆基显影剂、铋基显影剂、锶基显影剂、铜基显影剂、铝基显影剂和/或其组合。
在一个实施方式中，所述显影剂选自硫酸钡、氧化锆、碱式碳酸铋、碳酸锶、卤化锶和/或其组合。
在一个实施方式中，所述显影剂选自硫酸钡、氧化锆和/或其组合。
在一个实施方式中，所述增强相包括糊化后的淀粉。在一个实施方式中，所述糊化后的淀粉是通过选自醇沉、冷冻干燥和/或喷雾干燥中的一种或其组合的方法进行回收。在一个实施方式中，所述糊化后的淀粉通过冷冻干燥的方法进行回收。在一个实施方式中，所述冷冻干燥温度不高于-10℃、或不高于-20℃、或不高于-30℃、或不高于-40℃、或不高于-50℃、或不高于-60℃、或不高于-70℃、或不高于-80℃、或不高于-90℃、或不高于-100℃。
在一个实施方式中，所述糊化后的淀粉中直链淀粉的含量低于90％、低于80％、低于70％、低于60％、低于50％、低于40％、低于30％、低于20％、低于10％、或低于5％、或低于3％。
在一个实施方式中，所述淀粉包括选自普通玉米淀粉、蜡质玉米淀粉、高直链玉米淀粉、木薯淀粉和马铃薯淀粉中的一种或多种。在一个实施方式中，所述淀粉包含蜡质玉米淀粉和/或普通玉米淀粉。
在一个实施方式中，所述糊化后的淀粉粘度在0.1rad/s时小于104，在10rad/s时小于103。在一个实施方式中，所述糊化后的淀粉粘度在0.1rad/s时小于103，在10rad/s时小于102。在一个实施方式中，所述糊化后的淀粉膨胀度大于20％。在一个实施方式中，所述糊化后的淀粉在XRD衍射图谱中仅显示一个形状弥散且光滑的宽峰。
在一个实施方式中，所述淀粉扫描电镜图显示不规则片状；在一个实施方式中，所述淀粉扫描电镜图基本如图3-2中D6或D7所示。
在一个实施方式中，所述骨水泥具有抗压强度大于20MPa；在一个实施方式中，所述骨水泥具有抗压强度大于30MPa；在一个实施方式中，所述骨水泥具有抗压强度大于40MPa；在一个实施方式中，所述骨水泥具有抗压强度大于50MPa；在一个实施方式中，所述骨水泥具有抗压强度大于60MPa。
在一个实施方式中，所述骨水泥横截面经扫描电镜图显示无针状结构聚集；在一个实施方式中，所述骨水泥横截面经扫描电镜图基本如图9-4中G6所示；在一个实施方式中，所述骨水泥横截面经扫描电镜图基本如图9-4中G7所示。
在一个实施方式中，所述骨水泥具有初凝时间5min～30min，终凝时间10min～40min；在一个实施方式中，所述骨水泥具有初凝时间15min～30min，终凝时间20min～40min；在一个实施方式中，所述骨水泥具有初凝时间20min～30min，终凝时间25min～40min；在一个实施方式中，所述骨水泥具有初凝时间25min～30min，终凝时间35min～40min。
本申请还提供了一种淀粉材料用于制备上述骨水泥的用途。所述淀粉材料包含糊化后的淀粉。
本申请的骨水泥，实现了良好的操作性，易于注射、不易溃散且具有良好的机械性能，与自体骨可以很好匹配。特别是，本申请的骨水泥力学强度高，可用于承重结构骨部位。
附图说明
下面，将结合附图对本申请的一些具体实施方式进行进一步详细的说明，其中：
图1为添加淀粉增强相复合骨水泥强度的柱形图。
图2为改性淀粉的粘度结果图。
图3、4和5分别为淀粉扫描电镜图、XRD图和红外光谱图。
图6为骨水泥可注射性和抗溃散结果照片。
图7为复合骨水泥粘度结果图。
图8为骨水泥XRD图。
图9为骨水泥扫描电镜图。
图10为骨水泥的红外光谱图。
具体实施方式
为使本申请实施例的目的、技术方案和优点更加清楚，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。
在本文中没有相反表示的情况下，“基体相”是构成骨水泥主体的成分。在粉末状态下，基体相包含一种或多种磷酸钙盐粉末，例如，包括选自磷酸三钙(α型或β型)、二水合磷酸氢钙、无水磷酸氢钙、磷酸四钙、磷酸八钙、磷酸二氢钙、羟基磷灰石、氟磷灰石中的一种或多种。
粉末状态下的基体相中一种或多种磷酸钙盐粉末与液相混合后，可在初凝后继续进行自固化，最终可形成羟基磷灰石、透钙磷石和/或无定型磷酸钙。在一些实施方式中，粉末状态下的基体相中可包括偏酸性的磷酸钙盐粉末和偏碱性的磷酸钙盐粉末。
在一些实施方式中，粉末状态下的基体相中一种或多种磷酸钙盐粉末通过一系列的水化反应，最终形成一定程度结晶的羟基磷灰石(HA)。在一些实施方式中，基体相中还可添加羟基磷灰石(HA)晶体。添加的羟基磷灰石(HA)晶体，可以帮助基体相的水化过程，降低凝固时间，使得骨水泥基体相更容易发生自凝。
在一些实施方式中，粉末状态下的基体相包括磷酸三钙。磷酸三钙主要有低温相β-TCP和高温相α-TCP，α’-TCP三种晶型，其中，α-TCP晶型可通过急冷而在室温下稳定存在。在一些实施方式中，粉末状态下的基体相包含α-磷酸三钙(α-TCP)和二水合磷酸氢钙(DCDP)二者混合物。在一些实施方式中，包含α-磷酸三钙(α-TCP)和二水合磷酸氢钙(DCDP)的基体相中还可以添加磷酸四钙。通过基体相中添加磷酸四钙，可以提高硬化强度。在一些实施方式中，基体相含有至少两种磷酸钙盐粉末，所述不同种磷酸钙盐粉末通过干法混匀。在一些实施方式中，所述干法混匀包括球磨步骤，例如，将所述不同种磷酸钙盐粉末与玛瑙球，按照一定球料比干法混匀，例如球料比为1：2。在一些实施方式中，球磨后的混合磷酸钙盐经过筛处理，以控制基体相粉末的粒径水平，保证基体相颗粒与液相能够快速充分溶解，以促进水化反应进行。
在一些实施方式中，基体相中的磷酸钙盐可通过碳酸盐磷灰石制得。例如，将溶液中合成的碳酸盐磷灰石加热数小时，将所得固体进行研磨获得主要成分为磷酸钙钠、磷酸四钙和磷酸三钙的基体相粉末。
在一些实施方式中，基体相中磷酸钙盐粉末中α-磷酸三钙粉末通过高温煅烧后，再经急冷得到。例如，可先经高温保持4h，再经急冷得到α-磷酸三钙。
在一些实施方式中，基体相中除磷酸钙盐外，还可以添加化合物形式补充人体内微量元素锌、镁、锶和或氟等，以优化骨水泥的成骨性。
在没有相反表示的情况下，“增强相”是优化骨水泥性能的添加成分，例如淀粉。在一些实施方式中，淀粉包括选自普通玉米淀粉、蜡质玉米淀粉、高直链玉米淀粉、木薯淀粉和/或马铃薯淀粉中的一种或多种。
在一些实施方式中，淀粉可经物理或化学改性处理，例如经过糊化处理、分子交联处理、阳离子改性处理、钙离子改性处理、降低分子链长度处理、提高分支度处理、增加交联度的处理中的一者或多者。
在一些实施方式中，所述增强相为糊化后的淀粉。在一些实施方式中，所述糊化后的淀粉可以通过利用醇溶液沉淀的方法(又做“醇沉”)进行回收、喷雾干燥的方法进行回收和/或冷冻干燥的方法(又做“冻干”)进行回收。糊化可以破坏淀粉原本的结晶结构，消除淀粉原有的球形颗粒状态形成无定性的不规则的状态。淀粉经过糊化改性，可以在室温状态下溶解，可以和骨水泥的其他成分混合均匀，形成固化的三维网络。回收处理方法应尽可能保持无定形的不规则状态，以得到例如不规则的块状和/或片状等。在一些实施例中，淀粉经过糊化改性后的回收处理手段应尽可能避免微晶结构的产生，减少晶体数量，提高淀粉常温下溶胀能力。在一些实施例中，糊化后的淀粉，即经糊化改性回收所得的淀粉，可以实现以下一个或多个：具有较低的直链淀粉的含量，提高淀粉膨胀能力，以及降低淀粉在加入液相中形成的粘度。对淀粉进行上述处理，有助于提高骨水泥的理化性能。
在一些实施方式中，增强相的淀粉可以是通过醇沉方法回收的淀粉。示例性地，通过醇沉方法回收的淀粉可以通过如下方法制备，将淀粉与水或含水液体混合，使淀粉糊化以形成糊化的淀粉。将糊化后的淀粉进行冷却，冷却至室温后，向冷却后的淀粉中加入无水乙醇，室温下静置一段时间，分层后移除上清液，再向沉淀物中加入无水乙醇，再静置，经过滤、烘干、粉碎和过筛后，得到通过醇沉方法回收的淀粉。
在一些实施方式中，增强相的淀粉也可以是通过冷冻干燥方法回收的淀粉。示例性地，通过冷冻干燥方法回收的淀粉可以通过如下方法制备，将淀粉在搅拌和加热的条件下溶于水或含水液体中，使淀粉糊化，一定时间后形成糊化的淀粉，将所糊化后的淀粉冷却至室温后，在冷冻干燥设备中进行冷冻干燥后，再经粉碎和过筛，得到通过冷冻干燥方法回收的淀粉。
在一些实施方式中，增强相也可以是通过喷雾干燥方法回收的淀粉。示例性地，通过喷雾干燥方法回收的淀粉可以通过如下方法制备，将淀粉在搅拌和加热的条件下溶于水或含水液体中，使淀粉糊化，一定时间后形成糊化的淀粉，将糊化后的淀粉冷却至室温后，送入喷雾干燥设备，在喷雾干燥设备中进行喷雾干燥后，再经粉碎和过筛，得到通过喷雾干燥方法回收的淀粉。
在一些实施方式中，增强相可以选择具有较低的直链淀粉含量蜡质玉米淀粉和普通玉米淀粉，使蜡质玉米淀粉和普通玉米淀粉经过糊化改性并经冷冻干燥回收处理。在一些实施方式中，增强相具有较高的支链淀粉含量，较高的膨胀度，淀粉扫描电镜下的表观形貌显示松散的结构，成片状，具有较大接触面积，无明显结晶，X-射线衍射图谱显示不存在明显尖峰，呈现弥散且光滑的宽峰，溶于液相中形成较低的粘度。
本文中，在没有相反表示的情况下，“显影剂”是使得骨水泥具有显影性能的成分，例如，硫酸钡、氧化锆和/或其组合。在一些实施方式中，添加足以实现显影的显影剂，使骨水泥能够显影，可以满足术中对于显影的需求。
本文中，在没有相反表示的情况下，“固化液”是用于与粉末状态下的基体相、显影剂和/或增强相相混合以形成骨水泥浆体的液相。骨水泥浆体系糊状的骨水泥。常见的固化液包括选自磷酸氢二钠、磷酸氢钠、磷酸二氢钠、磷酸氢钾、磷酸氢二钾、稀磷酸、氢氧化钙、柠檬酸、甘油和/或丙二酸中的一者或多者。所述固化液可以是溶液等液体形式，也可以是经配制后形成液体的固体等形式。在一些实施方式中，固化液也可以是生理盐水、血清和/或血液等。
骨水泥浆体最终经过自固化后形成坚实的固体，即得到固体的骨水泥。在此过程中基体相与固化液中的水发生水化反应，例如，α-磷酸三钙(α-TCP)和二水合磷酸氢钙(DCDP)水化最终生成与人体骨组织的矿物相相似的羟基磷灰石。
本文中在没有相反表示的情况下，“普通磷酸钙骨水泥”是指仅含有基体相，不含有增强相和显影剂的磷酸钙骨水泥。
本文中在没有相反表示的情况下，“显影磷酸钙骨水泥”是指含有基体相，但除基体相之外，不含有增强相而含有显影剂的磷酸钙骨水泥。
本文中在没有相反表示的情况下，“复合骨水泥”是指含有基体相，除基体相之外，还同时含有增强相和显影剂的骨水泥。
对照例1:磷酸钙骨水泥的制备和性状表征
在本对照例中，依据如下方法制备普通磷酸钙骨水泥：将α-磷酸三钙
(α-TCP)和二水合磷酸氢钙(DCPD)按照9:1的质量比混合，加入3倍体积的无水乙醇，研磨混匀后倒入托盘中，放入50℃的烘箱干燥4h，然后升温至120℃干燥9h。烘干后的混合物研磨过60目筛得到基体相粉末。取基体相粉末加入磷酸氢二钠溶液，混合均匀后得到骨水泥浆体。对所得骨水泥进行如下测试。
1、力学测试。将骨水泥浆体填入模具，放入恒温恒湿箱(37℃，>60％RH)至一定硬度取出脱膜。再放入恒温恒湿箱(37℃，>60％RH)中固化72h后取出，得到固化后的骨水泥。采用万能力学测试机(上海衡翼精密仪器有限公司，规格HY-1080)，测试仪器采用10kN称重传感器，测试速度为0.5mm/min。所有样品的测量重复多次，以抗压强度(单位MPa)的平均值±标准差报告。本实施例中骨水泥抗压强度结果为15.4±1.8MPa。
2、可注射性测试。将骨水泥浆体封装入1mL注射器，排出孔直径2mm，固定在力学试验机上，以1mm/min的速度推注挤出，直到最大推力达到50N停止推注。观察注射情况并进行拍照。挤出水泥浆体的质量占浆体总质量的百分比定义为骨水泥的注射性。本实施例中骨水泥可注射性计算结果为<90％。
3、抗溃散性测试。将骨水泥浆体封装入1mL注射器，然后直接注射到装有37℃的去离子水的培养皿中，将培养皿放于振动装置(购自Scilogex USA，型号SK-O330-Pro)上，设置振动速度180r/min并保持1min，然后在去离子水中在37℃下，静置24h，如果骨水泥不发生碎裂，表明其具有良好的抗溃散性能，观察是否发生溃散并进行拍照。本实施例中骨水泥结果如图6-1所示。结果表明对照样磷酸钙骨水泥的抗溃散性不佳。
4、固化时间测试。固化时间的测试按照ASTM C191-03标准方法进行。将水泥浆体装入不锈钢模具(直径6毫米，高12毫米)，并用抹刀压扁。采用维卡仪的初凝针(重量113.4g，直径2.12mm)和终凝针(重量453.6g，直径1.06mm)分别测定骨水泥的初凝时间和终凝时间，每个样本进行五次测试，结果采用平均值±标准差表示。本实施例中骨水泥固化时间结果为3.3±0.5min，终凝时间9.0±0.4min。
5、骨水泥的表面形貌分析。将得到的骨水泥浆体填充到直径6毫米、高12毫米的圆柱形模具，待凝固后取出模具中的水泥样品，将圆柱形样品在37℃、>60％RH湿度下保存3天。之后将圆柱形样品掰断露出横截面，取样品粘附于双面导电胶上，样品横断面朝上。将样品置于离子溅射仪中喷金60s，将样品镀上一层导电薄膜，然后将样品盘送入扫描电镜样品室，调节样品台位置，将电压设置为15kV，开始进行扫描拍照。本实施例中骨水泥SEM结果如图9-1所示。
对照例2:显影磷酸钙骨水泥的制备和性状表征
本对照例中，依据如下方法制备显影磷酸钙骨水泥：按照对照例1中方法制备得到基体相粉末。将硫酸钡粉末(BaSO4)研磨、过200目筛。基体相粉末中加入一定量硫酸钡粉末研磨2min。将所得的混合粉末加入磷酸氢二钠溶液，混合均匀后得到硫酸钡作为显影剂的显影磷酸钙骨水泥浆体。
参考对照例1中的方法对所得骨水泥的力学强度、可注射性、抗溃散性、扫描电镜结构和固化时间进行评估。
进一步地，对所得骨水泥的孔隙率和密度进行分析。
1、孔隙率：将骨水泥浆体注入不锈钢模具中(直径6毫米、高12毫米)，待凝固后取出模具中的水泥样品，将样品在37℃、>60RH％下保存3天，在150℃烘箱中干燥5h，将干燥好的样品放入膨胀计中并保持水平，先进行低压分析。低压分析时，首先用压汞仪对样品抽真空，绝对压力值达到小于50μm Hg(0.0067kPa)，然后继续抽真空5min，通过虹吸法使汞充入膨胀计，接着通入氮气维持加压至0.5psi(3.4kPa)，低压分析结束后取出膨胀计放入高压室，通过油泵对汞施加压力，加压到60000psi，电容检测进汞量，并得到一系列不同压力下压入样品的汞的体积，从而求得样品的孔隙率。
2、密度：将骨水泥浆体注入不锈钢模具中(直径6毫米、高12毫米)，待凝固后取出样品。将样品在37℃饱和湿度下保存3天，取出样品后称重，质量为m1。然后，将水倒入密度天平中(上海越平，型号FA2104J)的烧杯，将吊篮挂在水中，确保没有气泡。将样品放入吊篮中，称取样品在水中的重量为m2。骨水泥样品的密度可按下式计算：
其中ρ表示骨水泥密度(g/cm3)，ρH2O表示水的密度(g/cm3),ρair表示空气的密度(g/cm3)，m1表示骨水泥在空气中的质量(g)，m2表示骨水泥在水中的质量(g)。平行测量多次，以平均值±标准差报告结果。
显影磷酸钙骨水泥的以上特性结果如下表1所示。
表1
实施例1:添加增强相的复合骨水泥的制备
基体相粉末参照对照例1中的方法制备；硫酸钡粉末研磨、过200目筛作为显影剂；预糊化淀粉(购自河南建杰淀粉制品有限公司)作为增强相。
在基体相粉末中添加增强相和适量硫酸钡显影剂进行混合。基体相和增强相的质量比为12:1、6:1、4:1或3:1。将所得的混合粉末研磨，然后与磷酸氢二钠溶液混合得到复合骨水泥浆体。将复合骨水泥浆体填充到不锈钢模具中直径6毫米、高12毫米，放入恒温恒湿箱(37℃，>60RH％)至一定硬度取出脱膜。再放入恒温恒湿箱(37℃，>60RH％)中稳定72h后取出，得复合骨水泥。对所得骨水泥样品的力学性能进行分析，结果如图1所示，其中，纵坐标“Compressive Strength”表示抗压强度；横坐标表示基体相和增强相的质量比，例如12:1表示增强相质量为基体相质量的1/12。
实施例2:不同类型显影剂的复合骨水泥
基体相粉末参照对照例1中的方法制备；硫酸钡粉末经研磨、过200目筛作为显影剂1；氧化锆显影剂粉末经研磨、过200目筛作为显影剂2；预糊化淀粉(购自河南建杰淀粉制品有限公司)作为增强相。
在基体相粉末中添加增强相和适量氧化锆显影剂进行混合。基体相和增强相的质量比为3:1。将所得的混合粉末研磨，然后与磷酸氢二钠溶液混合得到使用显影剂2的复合骨水泥浆体。将所得到的骨水泥浆体按实施例1方法测量其抗压强度，结果为57.7±4.0MPa。
重复前述步骤，将其中的氧化锆显影剂粉替换为等量硫酸钡显影剂粉末，得到使用显影剂1的复合骨水泥浆体，即氧化钡作显影剂的复合骨水泥浆体。将所得到的骨水泥浆体按实施例1方法测量其抗压强度，结果为46.2±1.8MPa。
上述结果显示，含有不同种类显影剂的复合骨水泥均取得了较为理想的力学强度。
实施例3:增强相的制备
选取蜡质玉米淀粉(秦皇岛骊骅有限公司)、普通玉米淀粉(秦皇岛骊骅有限公司)、高直链玉米淀粉(上海碧彩有限公司)、木薯淀粉(同春淀粉加工厂)和马铃薯淀粉(内蒙古华欧淀粉工业有限公司)，进行以下改性处理。
方法1：在1000mL烧杯中加入淀粉10g、去离子水490mL，并在沸水浴中搅拌并加热30min。冷却至室温后，向淀粉溶液中加入1500mL无水乙醇，室温下静置1小时。静置分层后倒出上清液，再向沉淀物中加入500ml无水乙醇，再静置一小时，抽滤后得到滤饼。将滤饼碾碎后置于40-45℃烘箱烘干过夜，将干燥的样品粉碎后过100目筛得到方法1处理的改性淀粉。
方法2：称取一定质量的淀粉，加入去离子水，配制质量分数为5％的淀粉浆，沸水浴加热并搅拌30min。待淀粉浆冷却至室温后冷冻，经冷冻干燥机处理。冷冻干燥结束后取出淀粉，粉碎后过筛得到方法2处理的改性淀粉。
经方法1处理的蜡质玉米淀粉、普通玉米淀粉、高直链玉米淀粉、木薯淀粉和马铃薯淀粉分别编号D1-D5；经方法2处理的蜡质玉米淀粉、普通玉米淀粉、高直链玉米淀粉、木薯淀粉和马铃薯淀粉分别编号D6-D10；未经处理的蜡质玉米淀粉、普通玉米淀粉、高直链玉米淀粉、木薯淀粉和马铃薯淀粉分别编号为D11-D15。
I.淀粉的直链淀粉含量
使用直链/支链测定试剂盒K-AMYL(购自Megazyme Int.,Ireland Ltd.Co.,Wicklow,Ireland)分别测定前述淀粉(对应实施例3中前述编号D1-D10的淀粉)的直链淀粉含量，计算公式如下：
平行测试至少3次，以保证数据可靠性，结果采用平均值±标准差表示。所得支链淀粉含量结果，如下表2所示。
表2

从上表结果可知，蜡质玉米淀粉具有最低的直链淀粉含量。同时，相对方法1处理的普通玉米淀粉，方法2处理的普通玉米淀粉取得了明显较低的直链淀粉含量。
II.淀粉的粘度
使用流变仪(购自TA Instruments，型号AR2000)分别测量前述不同淀粉(对应施例3中前述编号为D1-D10的淀粉)的粘度，测量时采用频率扫描，设置角频率扫描区间0.1-10rad/s，应变振幅为1％，在25℃观察材料性能的变化。
淀粉分别按照一定比例溶于去离子水，搅拌均匀后上样。样品粘度结果如图2所示，其中图2-1和图2-2分别显示了方法1处理的淀粉(对应实施例3中前述编号为D1-D5的淀粉)和方法2处理的淀粉(对应实施例3中编号为D6-D10的淀粉)的粘度。图中横坐标“Angular frequency”表示角频率,纵坐标“Complex viscosity”表示复数粘度。图中右上角标识相应淀粉编号为D1-D10。
由上图结果可知，全部淀粉均呈现剪切变稀。比较不同淀粉的粘度发现，蜡质玉米淀粉粘度最低。另外，冷冻干燥回收处理产生了更优的降低粘度效果，特别是对于普通玉米来说，冷冻干燥回收处理，相较于醇沉回收处理，粘度显示出了明显地进一步降低。
III淀粉的膨胀度
分别测量前述不同淀粉(对应实施例3中前述编号为D1-D10的淀粉)的膨胀度，具体步骤如下：
离心管中加入约100mg干基样品重量记为W，并且记录样品和离心管的总质量为W1，向离心管中加入10mL水震荡均匀，将离心管置于95℃水浴锅放置30min(期间每15min取出震荡摇匀)后取出。使用离心机(购自湖南湘仪，型号TD5A-WS)以4000g的速度离心20min，随后分离上清液，记录装有沉积物的离心管质量W2，膨胀度的计算公式如下：
平行测试至少3次，以保证数据可靠性，结果采用平均值±标准差表示，结果如表3所示。
表3
上表数据结果显示，相较于编号为D1-D5的淀粉，编号为D6-D10的样品取得了更高的膨胀度。其中，编号为D1和D6的淀粉具有相对更高的膨胀度。编号为D7的淀粉相较于编号为D2的淀粉具有明显更高的膨胀度。
IV.淀粉的表观形貌
通过扫描电镜(SEM)对淀粉的表观形貌进行表征(图3)。结果表明未经糊化淀粉呈球状颗粒，表面光滑(图3-3)。经方法1处理的改性淀粉呈不规则颗粒状(图3-1，其中左上角标识D1-D5分别对应淀粉编号D1-D5)。经方法2处理的改性淀粉呈片层状(图3-2，其中左上角标识D6-D10分别对应淀粉编号D6-D10)。淀粉经糊化，破坏了淀粉颗粒的原有结构。淀粉颗粒中的结晶区由紧密排列状态变为松散状态，不断吸水膨胀，形成不可逆的相变，膨胀到一定程度后，颗粒破裂，破坏原有的颗粒形状成无序的凝胶状，经干燥等回收处理后可呈现不规则的形状。
其中，方法1中回收过程中直链淀粉和支链淀粉分子的分支都重新趋向于平行排列，并相互靠拢，彼此与氢键结合后重新组合成混合微晶体，因此最终易呈现出不规则的块状，结构相对较为致密。而方法2中回收处理得到的淀粉，相比之下结构则更为松散，特别是编号D6和D7的淀粉，其电子显微镜下的表观形貌呈现不规则的片状，因为方法2中回收过程中干燥温度迅速下降，限制了淀粉链的移动，这赋予了方法2处理所得到的淀粉疏松多孔的形态。
V.淀粉的晶态
通过X射线衍射仪(购自德国Bruker，型号D8Discover)对淀粉的结晶形态进行分析。具体方法如下：将粉末淀粉样品平铺于样品台中，扫描条件：镍过滤的Cu Kα(nickel-filtered Cu Kα)射线，石墨单色管，管压40kV(V＝40kV)，电流40mA(I＝40mA)。扫描衍射角度为5～40°，扫描速度2°/min。
结果表明原淀粉(即未经改性处理的淀粉)中蜡质玉米淀粉、普通玉米淀粉和木薯淀粉为晶体结构为典型的A型，马铃薯淀粉和高直链玉米淀粉的晶体结构为B型(见图4-3)。经改性处理后，淀粉的晶体结构发生显著变化。经方法1处理后，淀粉晶体结构破坏，特别是蜡质玉米淀粉(编号D1)，无明显晶体衍射，为无定形结构(见图4-1)。经方法2处理后，淀粉晶体结构受到显著破坏，各淀粉无明显晶体衍射峰(见图4-2)。
从图中发现，图4-2中淀粉样品全部无明显结晶尖峰。特别是，图4-2中的蜡质玉米淀粉(编号D6)和普通玉米淀粉(编号D7)图谱仅显示唯一一个形状弥散的宽峰，且该宽峰形状光滑，没有明显凸出部分，表明相应的淀粉样品已经没有较为完整的结晶区域，淀粉结构极为松散，无定形程度高。相比较而言，其他的呈现多个弥散峰的样品，则仍然存在较小的微晶体结构。同时可观察到，相较于方法1处理的淀粉样品，方法2处理的淀粉样品更为彻底的失去了淀粉结晶结构，获得的淀粉结构更为松散。方法2中的回收过程可以更好限制淀粉链移动，使淀粉链之间联系更少，使淀粉很快越过老化温度，很好地避免了淀粉“回生”，因而可以得到结构更为松散的淀粉样品。
VI.淀粉的官能团表征
通过红外光谱仪(购自美国赛默飞，型号NicoletTM iS20)对实施例3中前述编号为D1-D15的淀粉进行官能团分析，具体方法如下：取1～2mg完全干燥的淀粉置于光谱分析仪器测试区域。设定扫描范围为500～4000cm-1，分辨率为0.25cm-1，进行测试。所得结果如图5所示。其中，图5-1表示经方法1处理的淀粉，分别对应淀粉编号D1-D5；图5-2表示经方法2处理的淀粉，分别对应淀粉编号D6-D10；图5-3表示未经糊化的原淀粉，分别对应淀粉编号D11-D15。
在淀粉的红外光谱图中，在2850～2900cm-1范围内为CH2中的C-H键的不对称伸缩振动峰，而羟基的伸缩振动吸收带出现在3000～3600cm-1，其构成了淀粉的总体结构，该区域主要由分子内、分子间和自由分子间羟基的伸缩振动产生的。1661～1623cm-1处的特征峰代表C＝O键的伸缩振动。C-C和C-O的伸缩振动峰在1145cm-1，C-O-C弯曲振动峰在995cm-1。
上述红外光谱图结果显示原淀粉及改性淀粉的吸收波谱图无明显变化，特征吸收峰位置也并没有发生明显的改变，说明改性后淀粉的基本化学结构没有发生变化，淀粉在改性处理过程中未发生化学反应，未产生新的官能团。
实施例4：不同改性淀粉作为增强相制备复合骨水泥及其表征
基体相粉末参照对照例1中的方法制备；硫酸钡粉末研磨、过200目筛作为显影剂；分别采用前述编号为D1～D10淀粉作为增强相按照如下描述方法制备骨水泥，所得骨水泥样品编号分别对应为G1～G10。
在基体相粉末中添加增强相和适量显影剂进行混合。基体相和增强相的质量比为3:1。将所得的混合粉末研磨2min，然后与磷酸氢二钠溶液混合得到复合骨水泥浆体。所得骨水泥浆体进一步固化形成固态的骨水泥。
参考对照例2中的方法分别对所得骨水泥的力学强度、可注射性、抗溃散性、固化时间、扫描电镜结构、孔隙率和密度进行评估，结果如表4所示。
表4
结果表明与对照样品相比(对照例1、对照例2)，添加改性淀粉D1～D10作为增强相显著提高了骨水泥的力学强度，且方法2处理的改性淀粉D6～D10所制备的骨水泥力学强度更高。此外原淀粉来源不同的增强相，骨水泥力学强度均有不同程度的提高。骨水泥G6-G10的固化时间较骨水泥G1-G5显著改善， 使得更长的操作时间成为可能。各组样品都具有良好的注射性和抗溃散性。方法2的处理可以使样品取得较低的孔隙率，较高的密度，取得更优的力学强度和更适于手术操作的固化时间。特别是其中编号为G6和G7的淀粉样品，显示了较低的孔隙率，较高的密度和高水平的力学强度。
实施例5:复合骨水泥的理化性质
I.复合骨水泥粘度分析
骨水泥粘度的测试使用流变仪(购自TA Instruments，型号AR2000)。分别选取淀粉样品D1-D5作为增强相，按照实施例4中的方法，将基体相与淀粉增强相及适量显影剂粉末混合，将所得的混合粉末进行2min研磨后，加入磷酸氢二钠溶液，得到均匀的骨水泥浆体。取1mL骨水泥浆体进行流变学测试。增强相分别采用实施例3淀粉样品D1-D5，所得骨水泥浆体对应编号为J1-J5。
不同频率下样品粘度结果如图7所示。图中横坐标“Angular frequency”表示角频率,纵坐标“Complex viscosity”表示复数粘度。右上角标识表示相应骨水泥浆体J1-J5。
对照例1中的普通磷酸钙骨水泥和对照例2中的显影磷酸钙骨水泥由于没有加入淀粉，因此不表现出明显粘性。
比较图7可发现，与淀粉的粘度特征相似，复合骨水泥也呈现剪切变稀的性质。复合骨水泥的粘度与其中增强相淀粉的粘度趋势一致。即，通过使用具有较低粘度的淀粉作为增强相，可以降低复合骨水泥的粘度，相应地复合骨水泥取得了更高的力学强度。较低的淀粉粘度可以影响其淀粉在骨水泥中的均匀分布情况，进而影响骨水泥的流动性能和力学性能。
II.复合骨水泥结晶分析
对复合骨水泥样品进行晶体结构分析。取实施例3中淀粉样品D1、D2、D3、D6、D7、D8作为增强相，参考实施例4的方法制备骨水泥样品(对应骨水泥编号为G1、G2、G3、G6、G7、G8)。将上述得到的骨水泥浆体注入直径6mm、高度12mm的圆柱形不锈钢模具中且从加入液相开始计时，待固化后推出样品，并将圆柱形样品在37℃、饱和湿度下分别放置3h和1天，之后将圆柱样品用研钵研磨成粉末。加入10％wt的硅粉作为内标并混合均匀。将混合后的粉末平铺于样品台中，扫描条件：镍被过滤的Cu Kα(nickel-filtered Cu Kα)射线，石墨单色管，管压40kV(V＝40kV)，电流40mA(I＝40mA)。扫描衍射角度为20～50°，扫描速度1.5°/min。结果如图8所示。其中图8-1表示反应3h的结果，图8-2表示反应1天的结果。图中横坐标“Degree(2θ)”表示峰位置,纵坐标“Intensity(a.u.)”表示衍射强度。图中标识表示相应骨水泥样品编号和反应时间。初始状态下骨水泥粉末具有位于2θ衍射角31°的α-TCP特征峰。复合骨水泥中磷酸钙盐发生水合反应后α-TCP特征峰逐渐消失，而位于2θ衍射角32°、47°和49°处羟基磷灰石的特征峰则随时间逐渐增加，α-TCP特征峰在3h后开始降低，1d后消失。同时，BaSO4的特征峰在凝固过程中保持恒定不变。淀粉增强相和BaSO4的加入并不会影响磷酸钙骨水泥水化反应最终产物羟基磷灰石的生成。
III.复合骨水泥官能团分析
通过红外光谱仪(购自美国赛默飞，型号NicoletTM iS20)对普通磷酸钙骨水泥和复合骨水泥进行官能团表征，方法如下：将骨水泥浆体注入直径6mm、高度12mm的圆柱形不锈钢模具中，然后将样品推出模具，并在37℃饱和湿度下保存3天使其完全反应固化。用研钵将样品研碎，取微量粉末样品置于光谱仪的测试区域，设定扫描范围为500～4000cm-1，分辨率为0.25cm-1，进行测试。
复合骨水泥的红外光谱图如图10所示；其中图10-1为方法1处理的淀粉作为增强相的复合骨水泥的红外光谱图；图10-2为方法2处理的淀粉作为增强相的复合骨水泥的红外光谱图和普通磷酸钙骨水泥的红外光谱图。其中， G1-G10分别对应相应编号的复合骨水泥，CPC表示普通磷酸钙骨水泥。
与普通磷酸钙骨水泥类似，图10中显示的复合磷酸钙骨水泥红外光谱中的大部分谱带归因于由DCPD和α-TCP反应结晶的羟基磷灰石。红外谱图中都存在PO4 3-谱带，主要集中在563cm-1、606cm-1、和1030-1090cm-1处的特征峰，1030-1090cm-1为PO4 3-的伸缩振动吸收峰，563cm-1、606cm-1处则是PO4 3-弯曲振动吸收峰。而1030cm-1和1120cm-1处的特征峰则对应淀粉和PO4 3-的C-O-C基团。淀粉所特有的有机基团的特征峰也被磷酸钙和羟基磷灰石的特征峰所覆盖。由此可见，复合骨水泥中的淀粉增强相并不会干扰基体相的化学组成，其并未参与化学反应，未产生新的基团。
实施例6：复合骨水泥的降解性能
将本申请含有淀粉增强相和显影剂的复合磷酸钙骨水泥注入羊骨，并持续跟踪观察上述注射有复合磷酸钙骨水泥(含淀粉增强相和显影剂的磷酸钙骨水泥的羊骨，发现降解发生在28周之后，即降解本申请的复合磷酸钙骨水泥(含淀粉增强相和显影剂的磷酸钙骨水泥)的降解周期为大于28周。由此可知，本申请的复合磷酸钙骨水泥(含淀粉增强相和显影剂的复合磷酸钙骨水泥)具有良好的降解性能。
综合前述实施例的结果，可以发现，相较于普通磷酸钙骨水泥，显影磷酸钙骨水泥和复合骨水泥均有力学强度的提升，但复合骨水泥的力学强度提升较为明显。通过控制增强相淀粉的特性，可以达到30MPa的力学强度，这一强度水平使骨水泥用于承重部位的骨结构中成为可能。特别是，在部分增强相淀粉的特性条件下(例如，冷冻干燥回收的改性蜡质玉米淀粉和改性普通玉米淀粉)，复合骨水泥的强度可以提高至50MPa以上。这一强度水平不仅使得复合骨水泥用于承重部位骨结构，同时可以实现良好的安全性。
添加改性淀粉的复合骨水泥，也可以实现固化时间的改善。普通磷酸钙骨水泥的初凝时间不足5min，终凝时间不足10min。添加未经糊化的淀粉，初凝时间大致为10min，终凝时间大致为15min。而上述实施例中的结果显示，添加经糊化的淀粉可以更有效地改善固化时间，例如改善初凝时间达到接近15min甚至略高于25min，同时改善终凝时间达到高于20min甚至略高于35min，这样的固化时间，使得骨水泥更适宜手术操作。实际应用时，为了满足骨水泥用于手术时的操作要求，通常要求固化时间达到约15min；更优地，固化时间可以进一步优化，如达到30min左右，以便获得充分的操作时间。充分的操作时间可以实现骨水泥的良好注射和填充，如固化时间过短，将骨水泥注射进入骨结构时，骨水泥过早固化，会导致浆体无法充分注射，也无法均匀和充分填充。
添加改性淀粉的复合骨水泥还可以提高可注射性和抗溃散性。可注射结果显示，普通磷酸钙骨水泥的可注射性结果不足90％，而含有改性淀粉增强相的复合骨水泥均取得了优良的可注射性，可注射性结果均大于90％。
从图6-3和6-4的照片中也可以观察到复合骨水泥被流畅光滑地从注射器中注出。50N是手术操作者最大推力，在此推力下可以实现流畅光滑注出，不出现断条，这意味着在实际操作中，可以实现充分的注射。
图6-3和6-4中也显示了骨水泥抗溃散性能的结果。改性处理后的淀粉作为增强相可以明显提高骨水泥的抗溃散性，在测试条件下保持了完整性，未出现溃散。综上可知，改性淀粉可以使复合骨水泥同时实现优异的可注射性和抗溃散性。
实施例4中的骨水泥性能结果结合实施例3中的淀粉特性结果显示，淀粉的特性显著影响骨水的性能参数。通过改变淀粉增强相，可以调整复合骨水泥参数，使骨水泥取得较高的力学强度、更适宜的固化时间，并同时兼具易于注射以及不易溃散的特性。例如，蜡质玉米淀粉、特别是冷冻干燥回收的蜡质玉米淀粉，在作为增强相时，在力学上表现出较高的强度，同时表现出了更适宜的固化时间、易于注射且不易溃散。再如，对于普通玉米淀粉，经冷冻干燥回收，与醇沉回收相比，表现出更好的流动性质，其可以使得骨水泥更容易注射，并且不易溃散，同时骨水泥的固化时间也得到了优化，更利于手术操作，且骨水泥的力学强度更高。通过糊化处理，特别是通过冷冻干燥方法回收时，可以改进增强相淀粉的特性和骨水泥的特性，使得骨水泥在固化时间、力学强度、注射性和抗溃散等方面取得更优的性能。
前述实施例中淀粉的扫描电镜结果显示，改性和回收方法显著影响了淀粉的表观形貌。通过冷冻干燥方法进行回收，蜡质玉米淀粉和普通玉米淀粉的电子显微镜下的表观形貌呈不规则片状，淀粉结构疏松多孔，与水可以形成更好的接触，易溶解形成凝胶状，常温下呈现良好的溶胀能力，也呈现较低的淀粉粘度，在骨水泥中使用时也可以取得良好的流动性，得到了较为均匀的骨水泥，取得了优良的力学强度，兼具良好的可操作性。
不同的淀粉晶体结构，可以影响骨水泥的性能参数。例如，经冷冻干燥回收处理的淀粉，可以更好保持结晶区域被彻底破坏的状态。与醇沉回收处理的淀粉相比，冷冻干燥回收处理的淀粉可以更大程度地改善骨水泥的固化时间，提高力学强度。
通过观察扫描电镜图分析骨水泥的表面形貌可以发现，普通磷酸钙骨水泥以及显影磷酸钙骨水泥微观的表面形貌存在较多的明显针状结构。明显针状结构属于典型的羟基磷灰石晶体的形貌。而含有淀粉增强相的复合骨水泥，也可以观察到相同的针尖状的晶体颗粒，表明改性淀粉加入后，CPC的水化产物并无明显变化。令人惊奇的是，普通磷酸钙骨水泥以及显影磷酸钙骨水泥存在比较明显的针状结构成簇聚集，而含有淀粉增强相的复合骨水泥则显示出较小的针状结构聚集，且孔洞也更小，扫描电镜图中的表面形貌结构呈现出更为均匀，更少的针状晶体结构聚集，相对应地骨水泥可以取得更高的力学强度、相对更优的固化时间，操作性能更佳。特别地，蜡质玉米淀粉和普通玉米淀粉作为增强相时，相对其他样品展现出的表面形貌更为均匀，孔洞更小。
由上述实施例中结果分析可知，通过调整淀粉的特性，得到较低的直链淀粉含量，较低的淀粉粘度，较高的淀粉膨胀能力，较为松散的表观形貌，取得更低的骨水泥孔隙率和更高的骨水泥密度，影响骨水泥表面形貌，减弱甚至消除针状晶体结构的聚集，可以实现骨水泥的性能的提升，例如提高力学强度，获得更便于操作的固化时间并提高操作性能等。令人惊讶地，通过控制淀粉增强相的特性，可以使得复合骨水泥的抗压强度相对于普通磷酸钙骨水泥提高4倍以上，到达50～60MPa，充分满足承重骨的力学要求，同时兼有良好的可注射性和抗溃散性。另外，本申请的复合磷酸钙骨水泥在可降解性能等方面均表现出了良好的效果。与目前现有的骨水泥相比，在强度、固化时间、降解性、可注射性和抗溃散性等主要性能上均表现出优势，可以实现良好的综合效果。
除非另行规定，本文中使用的所有技术和科学术语具有本领域普通技术人员通常理解的相同含义。在矛盾的情况下，将以本文(包括定义)为准。
本文所用的术语“包含”、“包括”、“具有”、“可以”、“含有”及其变型意于为开放式的连接短语、术语或词语，其不排除附加操作或结构的可能性。除非上下文清楚地另行规定，单数形式“一”和“该”包括复数对象。本公开还考虑其它实施方式“包含本文中给出的实施方式或要素”、“由本文中给出的实施方式或要素组成”和“基本由本文中给出的实施方式或要素组成”，无论是否明确提出。
连接术语“或”包括与该连接术语相关的一个或多个所列要素的任何和所有组合。例如，短语“包含A或B的装置”可以是指包括A但其中不存在B的装置、包括B但其中不存在A的装置，或其中存在A和B两者的装置。短语“A、B、...和N中的至少一种”或“A、B、...N或其组合中的至少一种”在最广义上定义以意指选自A、B、...和N中的一种或多种要素，也就是说， 要素A、B、...或N中的一种或多种的任何组合，包括单独的任一要素，或与一种或多种所述其它要素的组合，这也可能组合地包括没有列举的附加要素。
在本文中，不论是否明确指出,所有数值都被假定为可用术语“大约”或“约”进行修饰。在使用数值的上下文中,术语“大约”或“约”通常是指本领域的技术人员将认为等同于所引用的值(即，具有相同功能或结果)及其邻近的一个范围。“大约”或“约”也应被认为公开了由两个端点的绝对值限定的范围。例如，表述“大约2至大约4”也公开了范围“2至4”。术语“大约”或“约”可以是指所示数值的+或-10％。例如，“大约10％”可以是指9％至11％的范围，“大约1”可以是指0.9-1.1。在许多情况下，术语“大约”或“约”可包括被四舍五入至最近的有效数字的数值，例如“大约1”也可能是指0.5至1.4。除非另有规定外,其他对术语“大约”的使用(即在除了使用数值以外的上下文中)可被假定为具有其普通和习惯定义。
上述实施例仅供说明本发明之用，而并非是对本发明的限制，有关技术领域的普通技术人员，在不脱离本发明范围的情况下，还可以做出各种变化和变型，因此，所有等同的技术方案也应属于本发明公开的范畴。

Claims (17)

  1. 一种骨水泥，其包括基体相、增强相、足以实现显影的量的显影剂与固化液，其中所述基体相包括磷酸钙盐，所述固化液至少能够与所述基体相中的磷酸钙盐反应形成羟基磷灰石，所述增强相包括淀粉，所述淀粉是糊化后的淀粉，其中所述糊化后的淀粉中直链淀粉的含量低于90％、低于80％、低于70％、低于60％、低于50％、低于40％、低于30％、低于20％、低于10％、或低于5％、或低于3％。
  2. 根据权利要求1所述的骨水泥，其中所述增强相质量为基体相质量的1％～100％、或5％～95％、或10％～50％。
  3. 根据权利要求1所述的骨水泥，其中所述基体相包括选自磷酸三钙、二水合磷酸氢钙、无水磷酸氢钙、磷酸四钙、磷酸八钙、磷酸二氢钙、羟基磷灰石、氟磷灰石中的一者或多者。
  4. 根据权利要求3所述的骨水泥，其中所述基体相包括磷酸三钙和二水合磷酸氢钙二者混合物。
  5. 根据权利要求1所述的骨水泥，其中所述固化液包括选自磷酸氢二钠、磷酸氢钠、磷酸二氢钠、磷酸氢钾、磷酸氢二钾、稀磷酸、氢氧化钙、柠檬酸、甘油和/或丙二酸中的一者或多者。
  6. 根据权利要求1所述的骨水泥，其中所述糊化后的淀粉通过选自醇沉、冷冻干燥和/或喷雾干燥中的一种或其组合的方法进行回收。
  7. 根据权利要求6所述的骨水泥，其中所述冷冻干燥温度不高于-10℃、或不高于-20℃、或不高于-30℃、或不高于-40℃、或不高于-50℃、或不高于-60℃、或不高于-70℃、或不高于-80℃、或不高于-90℃、或不高于-100℃。
  8. 根据权利要求1所述的骨水泥，其中所述淀粉包括选自普通玉米淀粉、蜡质玉米淀粉、高直链玉米淀粉、木薯淀粉和马铃薯淀粉中的一种或多种。
  9. 一种骨水泥的制备方法，所述方法包括：将基体相、增强相、足以实现显影的量的显影剂与固化液混合形成骨水泥浆体，其中所述基体相包括磷酸钙盐，所述固化液至少能够与所述基体相中的磷酸钙盐反应形成羟基磷灰石，所述增强相包括糊化后的淀粉，其中所述糊化后的淀粉中直链淀粉的含量低于90％、低于80％、低于70％、低于60％、低于50％、低于40％、低于30％、低于20％、低于10％、或低于5％、或低于3％。
  10. 根据权利要求9所述的方法，其中所述增强相质量为基体相质量的1％～100％、或5％～95％、或10％～50％。
  11. 根据权利要求9所述的方法，其中所述淀粉包括选自普通玉米淀粉、蜡质玉米淀粉、高直链玉米淀粉、木薯淀粉和马铃薯淀粉中的一种或多种。
  12. 一种淀粉材料用于制备骨水泥的用途,所述淀粉材料包含糊化后的淀粉，所述糊化后的淀粉中直链淀粉的含量低于90％、低于80％、低于70％、低于60％、低于50％、低于40％、低于30％、低于20％、低于10％、或低于5％、或低于3％。
  13. 根据权利要求12所述的用途，其中所述糊化后的淀粉通过选自醇沉、冷冻干燥、或者喷雾干燥中的一者或多者的方法进行回收。
  14. 如权利要求13所述的用途，其中所述冷冻干燥温度不高于-10℃、或不高于-20℃、或不高于-30℃、或不高于-40℃、或不高于-50℃、或不高于-60℃、或不高于-70℃、或不高于-80℃、或不高于-90℃、或不高于-100℃。
  15. 根据权利要求12所述的用途，其中所述淀粉包括选自普通玉米淀粉、蜡质玉米淀粉、高直链玉米淀粉、木薯淀粉和马铃薯淀粉中的一种或多种。
  16. 一种用于制备骨水泥的试剂盒，所述试剂盒包括基体相、增强相、和足以实现显影的量的显影剂；其中所述增强相包括糊化后的淀粉，其中所述糊化后的淀粉中直链淀粉的含量低于90％、低于80％、低于70％、低于60％、低于50％、低于40％、低于30％、低于20％、低于10％、或低于5％、或低于3％，其中所述糊化后的淀粉通过冷冻干燥的方法进行回收。
  17. 根据权利要求16所述的试剂盒，所述试剂盒还包括液相部分，所述液相部分，包括固化液，所述固化液至少能够与所述基体相中的磷酸钙反应形成羟基磷灰石。
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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1785443A (zh) * 2005-10-20 2006-06-14 华南理工大学 应用变性淀粉提高磷酸钙骨水泥抗溃散性能的方法
US20070224286A1 (en) * 2004-06-25 2007-09-27 Kutty Thundyil Raman N Process for Preparing Calcium Phosphate Self-Setting Bone Cement, the Cement So Prepared and Uses Thereof
CN101530630A (zh) * 2009-04-17 2009-09-16 华南理工大学 一种x光显影性磷酸钙骨水泥及其制备方法与应用
CN102526798A (zh) * 2012-01-18 2012-07-04 华东理工大学 可注射复合骨水泥及其制备方法
CN104056305A (zh) * 2014-04-24 2014-09-24 安泰科技股份有限公司 一种磷酸钙基复合自固化骨修复材料及其制备方法
CN108157942A (zh) * 2017-11-17 2018-06-15 中国林业科学研究院林产化学工业研究所 一种银杏糊化淀粉喷雾包埋羟基酪醇的方法
CN113082296A (zh) * 2021-04-26 2021-07-09 东南大学 一种具有良好可注射性的磷酸钙骨水泥及其制备方法

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070224286A1 (en) * 2004-06-25 2007-09-27 Kutty Thundyil Raman N Process for Preparing Calcium Phosphate Self-Setting Bone Cement, the Cement So Prepared and Uses Thereof
CN1785443A (zh) * 2005-10-20 2006-06-14 华南理工大学 应用变性淀粉提高磷酸钙骨水泥抗溃散性能的方法
CN101530630A (zh) * 2009-04-17 2009-09-16 华南理工大学 一种x光显影性磷酸钙骨水泥及其制备方法与应用
CN102526798A (zh) * 2012-01-18 2012-07-04 华东理工大学 可注射复合骨水泥及其制备方法
CN104056305A (zh) * 2014-04-24 2014-09-24 安泰科技股份有限公司 一种磷酸钙基复合自固化骨修复材料及其制备方法
CN108157942A (zh) * 2017-11-17 2018-06-15 中国林业科学研究院林产化学工业研究所 一种银杏糊化淀粉喷雾包埋羟基酪醇的方法
CN113082296A (zh) * 2021-04-26 2021-07-09 东南大学 一种具有良好可注射性的磷酸钙骨水泥及其制备方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LIU, BIN: "Research on Related Properties of Starch-Reinforced Calcium Phosphate Bone Cement", MEDICINE AND HEALTH SCIENCES, CHINA MASTER'S THESES FULL-TEXT DATABASE, vol. 5, 15 May 2018 (2018-05-15), ISSN: 1674-0246 *
LIU, CHUN: "Design, Preparation and Application of New Calcium Phosphate Composite Bone Cement in Strengthening Cannulated Pedicle Screw Fixation", ENGINEERING SCIENCE AND TECHNOLOGY I, CHINA MASTER'S THESES FULL-TEXT DATABASE, no. 4, 15 April 2020 (2020-04-15), ISSN: 1674-0246 *

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