An injectable bone cement with low heat release and low elastic modulus, its preparation method and uses

Abstract

The present invention discloses an injectable bone cement with low heat release and low elastic modulus, and a preparation method and use thereof. The preparation method comprises the following steps: performing double-bond modification on hydroxyapatite powder; connecting the double-bond modified hydroxyapatite powder with perfluorinated monomers through free radical polymerization to obtain perfluorinated modified hydroxyapatite; mixing the perfluorinated modified hydroxyapatite, alendronate sodium and benzoyl peroxide as a solid phase, adding the mixture to a liquid phase poly(methyl methacrylate) prepolymer, stirring and dispersing the mixture fully, adding N,N-dimethylaniline and stirring and dispersing again, and curing at a simulated human body temperature to obtain the injectable bone cement with low heat release and low elastic modulus. The present invention loads the anti-osteoporosis drug alendronate sodium in the bone cement, and promotes the generation of new bone by inhibiting the proliferation of osteoclasts.

Description

Technical Field

[0001] The invention relates to the field of orthopedic medical materials, and in particular to an injectable bone cement with low exotherm and low elastic modulus, and a preparation method and application thereof. Background Art

[0002] Osteoporosis is one of the most common diseases in the clinic and is a prominent problem in various common diseases around the world. Among them, osteoporotic fractures are more prominent and often occur in middle-aged and elderly people, with the highest incidence in postmenopausal women. The disease is accompanied by severe pain and limited activity, which poses a serious threat to the health of patients. In recent years, the method of minimally invasive vertebroplasty to inject bone cement to treat osteoporotic vertebral compression fractures has achieved considerable results in reducing vertebral pain and preventing vertebral collapse.

[0003] Methyl methacrylate (PMMA) bone cement can provide excellent mechanical support for the vertebral body and has become a commonly used material for vertebroplasty in clinical practice. Hydroxyapatite (HA), one of the main components of bones, has excellent bioactivity and biocompatibility. It can combine with the surrounding matrix bone through chemical reactions, and promote bone remodeling and new bone formation through mutual absorption and replacement with bone tissue. Among them, nanohydroxyapatite (n-HA) can effectively improve its solubility and bioactivity at a larger specific surface area, and has better practicality.

[0004] At the site of osteoporotic fracture, the oxygen level drops significantly due to the destruction of bones and blood vessels. The resulting hypoxia inhibits cell metabolism, causes cell death, and delays bone healing. At the same time, the massive proliferation of osteoclasts also inhibits bone repair and healing. PMMA bone cement has many defects in the clinical application of treating osteoporotic fractures. The large amount of heat released during the curing of bone cement raises the local temperature of bone tissue to above 60°C, which will damage bone tissue when it is higher than the tolerance temperature of bone tissue (about 47°C). In addition, PMMA bone cement has poor adhesion to human tissue and is not biologically active, and is prone to loosening after implantation. At the same time, the elastic modulus of methyl methacrylate bone cement is generally between 1700MPa and 3700MPa, and the high elastic modulus increases the risk of adjacent bone fractures. Although nanohydroxyapatite has excellent biocompatibility and osteoconductivity, its main mechanical properties are insufficient, and when it is compounded with polymers, due to factors such as agglomeration and poor adhesion, it will lead to problems of decreased mechanical strength and insufficient load-bearing capacity. Summary of the invention

[0005] The purpose of the present invention is to provide an injectable bone cement with low exotherm and low elastic modulus, and a preparation method and use thereof, wherein the anti-osteoporosis drug alendronate sodium is loaded into the bone cement to promote the formation of new bone by inhibiting the proliferation of osteoclasts.

[0006] In one aspect of the present invention, the present invention provides a method for preparing an injectable bone cement with low exotherm and low elastic modulus. According to an embodiment of the present invention, the method comprises the following steps:

[0007] (1) double-bond-modifying hydroxyapatite powder;

[0008] (2) connecting the double-bond-modified hydroxyapatite powder with a perfluorinated monomer through free radical polymerization to obtain perfluorinated modified hydroxyapatite;

[0009] (3) Perfluoro-modified hydroxyapatite, sodium alendronate and dibenzoyl peroxide are mixed as a solid phase and added to a liquid phase polymethyl methacrylate prepolymer. After sufficient stirring and dispersion, N,N-dimethylaniline is added and stirred and dispersed again, and solidified at a simulated human body temperature to obtain an injectable bone cement with low exotherm and low elastic modulus.

[0010] In addition, the method for preparing an injectable bone cement with low exotherm and low elastic modulus according to the above embodiment of the present invention may also have the following additional technical features:

[0011] In some embodiments of the present invention, the step (1) specifically comprises the following steps: dissolving hydroxyapatite, hexamethylene diisocyanate and dibutyltin dilaurate in anhydrous N,N-dimethylformamide, heating under condensation reflux and nitrogen protection, dissolving an appropriate amount of hydroxyethyl methacrylate in N,N-dimethylformamide, slowly injecting into the above system, stirring and centrifuging, washing with dichloromethane for multiple times and collecting powder, fully drying, grinding and crushing with a mortar to obtain double bond-modified hydroxyapatite, whose structural formula is:

[0012]

[0013] In some embodiments of the present invention, the molar ratio of hydroxyapatite, hexamethylene diisocyanate and hydroxyethyl methacrylate is 1:1-3:3-10, the reaction temperature of the whole reaction process is 40-70°C, the heating time is 6-18h under condensation reflux and nitrogen protection conditions, the drying temperature is 35-50°C, and the drying time is 12-36h.

[0014] The synthesis route of the double bond modified hydroxyapatite HA-CH=CH2 is:

[0015]

[0016] In some embodiments of the present invention, step (2) specifically includes the following steps: Dissolve double-bond modified hydroxyapatite, perfluorinated monomer, and azobisisobutyronitrile in anhydrous N,N-dimethylformamide and place them in a sealed tube. Freeze and degas three times under nitrogen, and then perform flame sealing under vacuum. Place it in an oil bath and react for a sufficient time, then cool to terminate the reaction. Wash it multiple times with dichloromethane and collect the powder. Dry it thoroughly, grind it with a mortar and pestle to obtain perfluorinated modified hydroxyapatite, and its structural formula is:

[0017]

[0018] In some embodiments of the present invention, the preparation method of the perfluorinated monomer includes the following steps: Dissolve perfluorononyl alcohol, isocyanatoethyl methacrylate, and triethylamine in anhydrous tetrahydrofuran, heat and stir, remove tetrahydrofuran by vacuum rotary evaporation to obtain a crude product, use a mixed solution of petroleum ether and ethyl acetate as the eluent, purify it by silica gel column chromatography, and then dry it to obtain the perfluorinated monomer, and its structural formula is as follows:

[0019]

[0020] In some embodiments of the present invention, during the preparation of the perfluorinated modified hydroxyapatite, the molar ratio of double-bond modified hydroxyapatite, perfluorinated monomer, and azobisisobutyronitrile is 1:3 - 10:0.1 - 0.5, the reaction temperature is 65 - 85 °C, the reaction time is 48 - 72 h, the drying temperature is 30 - 50 °C, and the freezing temperature is -50 to -80 °C.

[0021] During the preparation of the perfluorinated monomer, the molar ratio of perfluorononyl alcohol to isocyanatoethyl methacrylate is 1:1 - 5, the reaction temperature is 40 - 60 °C, the reaction time is 12 - 36 h, the volume ratio of petroleum ether to ethyl acetate is 6:1, the drying temperature is 35 - 45 °C, and the drying time is 8 - 16 h.

[0022] The synthesis route of the FOM is:

[0023]

[0024] The synthesis route of the perfluorinated modified hydroxyapatite is:

[0025]

[0026] In some embodiments of the present invention, step (3) specifically includes the following steps: using methyl methacrylate prepolymer solution as the liquid phase, and a mixture of perfluorinated modified hydroxyapatite, alendronate sodium, and benzoyl peroxide as the solid phase. After adding an appropriate amount of N,N-dimethylaniline, the two phases are fully mixed and then heated and cured to obtain the injectable bone cement with low exotherm and low elastic modulus. Among them, the preparation method of the methyl methacrylate prepolymer solution is as follows: the methyl methacrylate solution dissolved with the initiator is heated in a water bath for a certain time, then the heating is stopped, and it is placed in cold water to cool to terminate the reaction.

[0027] In some embodiments of the present invention, the mass ratio of the liquid phase to the solid phase is 1:0.05 - 0.5. In the solid phase, the mass ratio of perfluorinated modified hydroxyapatite to alendronate sodium is 1:0.5 - 3, the mass of benzoyl peroxide is 0.2% - 3% of the mass of the methyl methacrylate prepolymer solution, the mass of N,N-dimethylaniline is 1% - 3% of the mass of the methyl methacrylate prepolymer solution, the curing temperature is 36 - 37 °C, and the curing time is 15 - 60 min.

[0028] The initiator is benzoyl peroxide or azobisisobutyronitrile, and the water bath heating temperature is 70 - 90 °C. The mass of the initiator is 0.5% - 2.5% of the mass of the polymethyl methacrylate prepolymer solution.

[0029] On the other hand, the present invention provides an injectable bone cement with low exotherm and low elastic modulus prepared by the preparation method of the injectable bone cement with low exotherm and low elastic modulus described above.

[0030] On the other hand, the present invention provides the application of the injectable bone cement with low exotherm and low elastic modulus in the preparation of an implant material for the treatment of osteoporotic fractures.

[0031] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0032] 1) In the present invention, perfluorinated grafted hydroxyapatite is prepared and mixed with alendronate sodium and the oxidant benzoyl peroxide as the solid phase, and is poured into the liquid polymethyl methacrylate prepolymer according to a certain ratio and stirred evenly. At the same time, a certain amount of N,N-dimethylaniline reducing agent is added to prepare an injectable bone cement for the treatment of osteoporotic fractures with low exotherm, low elastic modulus, and the functions of inhibiting osteoclast proliferation and carrying oxygen. Each step of the reaction is safe and reliable, the operation is simple, and the conversion rate of each step is relatively high.

[0033] 2) Through the grafting of the hydrophobic polymer on hydroxyapatite, the interfacial binding property between its surface and the polymer is improved, enhancing the dispersion effect in the PMMA polymer.

[0034] 3) After the hydroxyapatite is modified with double bonds, a functional perfluoropolymer is grafted. The perfluorinated molecules can carry oxygen and promote angiogenesis and the proliferation of bone marrow stem cells by continuously releasing oxygen, thus accelerating the healing of bone tissue. As a representative anti-osteoporosis drug, alendronate sodium has a good affinity for bones, can inhibit the activity of osteoclasts and promote calcium intake. Alendronate sodium and the perfluorinated molecules in the perfluorinated modified hydroxyapatite act synergistically to promote the treatment of osteoporosis. In addition, by means of free radical polymerization, perfluorinated monomers are grafted onto hydroxyapatite, which can effectively increase the grafting amount to improve the interfacial dispersion of hydroxyapatite in organic polymers, and endow the bone cement with the function of carrying oxygen to improve the treatment effect of osteoporotic fractures.

[0035] 4) The bone cement is further cured under the redox system and acts jointly with the heat dissipating agent alendronate sodium and the modified hydroxyapatite, greatly reducing the heat released during the curing of the bone cement and lowering the maximum exothermic temperature below 43°C, playing a protective role for bone tissue. In addition, the bone cement prepared by the present invention has excellent drug release properties, mechanical properties and injectability, and its elastic modulus is between 700-900 MPa, having potential application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 is a schematic diagram of the preparation process of an injectable bone cement with low exotherm and low elastic modulus in an embodiment of the present invention;

[0037] Figure 2 is the FT-IR spectra of hydroxyapatite (HA), isocyanate group modified hydroxyapatite (HA-NCO) and double bond modified hydroxyapatite (HA-CH=CH2) in Example 1 of the present invention;

[0038] Figure 3 is the 1H NMR spectrum of the perfluorinated monomer in Example 1 of the present invention;

[0039] Figure 4 is the FT-IR spectra of the perfluorinated monomer (FOM), double bond modified hydroxyapatite (HA-CH=CH2) and perfluorinated modified hydroxyapatite (HA-PFOM) in Example 1 of the present invention;

[0040] Figure 5 is the XRD spectra of hydroxyapatite (HA), double bond modified hydroxyapatite (HA-CH=CH2) and perfluorinated modified hydroxyapatite (HA-PFOM) in Example 1 of the present invention;

[0041] Figure 6 is the thermogravimetric diagram of hydroxyapatite (HA), double bond modified hydroxyapatite (HA-CH=CH2) and perfluorinated modified hydroxyapatite (HA-PFOM) in Example 1 of the present invention;

[0042] Figure 7 This is the XPS spectrum of the perfluorinated modified hydroxyapatite (HA-PFOM) in Example 1 of the present invention;

[0043] Figure 8 This is the temperature-time graph of the injectable bone cement with low exotherm and low elastic modulus in Examples 1-4 of the present invention, where 10%, 20%, 30%, and 40% correspond to Examples 1-4 in sequence;

[0044] Figure 9 This is the setting time graph of the injectable bone cement with low exotherm and low elastic modulus in Examples 1-4 of the present invention;

[0045] Figure 10 This is the compressive strength graph of the injectable bone cement with low exotherm and low elastic modulus in Examples 1-4 of the present invention;

[0046] Figure 11 This is the elastic modulus graph of the injectable bone cement with low exotherm and low elastic modulus in Examples 1-4 of the present invention;

[0047] Figure 12 This is the flexural strength graph of the injectable bone cement with low exotherm and low elastic modulus in Examples 1-4 of the present invention;

[0048] Figure 13 This is the injectability graph of the injectable bone cement with low exotherm and low elastic modulus in Examples 1-4 of the present invention, where Figures (a), (b), (c), and (d) correspond to Examples 1-4 in sequence;

[0049] Figure 14 This is the weight loss rate graph of the injectable bone cement with low exotherm and low elastic modulus in Examples 1-4 of the present invention after being soaked in plasma solution for 7 days;

[0050] Figure 15 This is the release rate graph of alendronate sodium drug of the injectable bone cement with low exotherm and low elastic modulus in Example 4 of the present invention. Detailed implementation manners

[0051] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0052] Example 1

[0053] A preparation method of an injectable bone cement with low exotherm and low elastic modulus includes the following steps:

[0054] (1) Synthesis of double bond modified hydroxyapatite (HA-CH=CH2): Dissolve 1 g of hydroxyapatite (HA), 1 g of hexamethylene diisocyanate (HDI), and 2 drops of dibutyltin dilaurate (DBTDL) in 30 mL of anhydrous DMF, and react at 45 °C for 8 h under reflux condensation and nitrogen protection to obtain isocyanate group modified hydroxyapatite (HA-NCO). Dissolve 1.10 g of 2-hydroxyethyl methacrylate (HEMA) in 5 mL of DMF, slowly inject it into the above reaction system, stir overnight, centrifuge, and separate the particles by centrifugation and redispersion cycles with dichloromethane multiple times. Collect the powder and place it in a vacuum oven at 35 °C to dry thoroughly for 24 h, and grind it with a mortar to obtain a white powder HA-CH=CH2.

[0055] As Figure 2 shown, the successful synthesis of HA-NCO was proved by the absorption peak of -NCO at 2273 cm -1 . The successful synthesis of HA-CH=CH2 was proved by the appearance of the absorption peak of carbon-carbon double bond at 1680 cm -1 and the absorption peak of carbonyl at 1729 cm -1 , as well as the disappearance of the isocyanate group absorption peak.

[0056] (2) Synthesis of perfluorinated monomer (FOM): Dissolve 1 g of perfluorononanol, 0.3 g of isocyanatoethyl methacrylate, and 0.01 g of triethylamine in 15 mL of anhydrous tetrahydrofuran, heat and react at 50 °C for 24 h, and then remove tetrahydrofuran by vacuum rotary evaporation to obtain a crude product. Use a mixed solution of petroleum ether:ethyl acetate with a volume ratio of 6:1 as the eluent, purify it by silica gel column chromatography, evaporate the excess solvent, and dry it in a vacuum oven at 35 °C for 12 h to obtain a white powder FOM.

[0057] As Figure 3 shown, the successful synthesis of the product FOM was proved by the absorption peaks of the newly formed double bond and methyl after the reaction.

[0058] (3) Synthesis of HA-PFOM: Dissolve 0.5 g of double bond modified hydroxyapatite (HA-CH=CH2), 1.5 g of perfluorinated monomer (FOM), and 10 mg of azobisisobutyronitrile (AIBN) in 10 mL of anhydrous DMF and load it into a sealed tube. Freeze and degas three times under a nitrogen atmosphere and at -80 °C, and after vacuum flame sealing, react at 75 °C for 60 h, cool to terminate the reaction, and separate the particles by centrifugation and redispersion cycles with dichloromethane multiple times. Collect the powder and place it in a vacuum oven at 35 °C to dry thoroughly for 18 h, and grind it with a mortar to obtain a white powder HA-PFOM.

[0059] As Figure 4 shown, after the reaction, at 1239 cm -1Absorption peak of -CF3 at 1204 cm -1 and 1150 cm -1 Asymmetric and symmetric absorption peaks of -CF2 at, and the absorption peak of the carbonyl group at 1723 cm -1 proved the successful grafting of HA-PFOM.

[0060] As Figure 5 shown, the functionalized products HA-CH=CH2 and HA-PFOM showed the same peaks as HA, which confirmed that the grafting reaction did not cause any crystal changes and the formation of secondary phases, and still had good crystallinity.

[0061] As Figure 6 shown, it was calculated that the grafting rate of the double bond of hydroxyapatite was 23.1%, and the copolymerization rate of the double bond-modified hydroxyapatite and the perfluoromonomer was 0.75:1, that is, an average of 0.47 perfluoromonomers were grafted onto each hydroxyl group of hydroxyapatite.

[0062] As Figure 7 shown, the successful modification of hydroxyapatite was illustrated by the absorption peaks of fluorine and calcium elements.

[0063] (4) Preparation of methyl methacrylate prepolymer solution: 100 mg of benzoyl peroxide (BPO) was dissolved in 20 g of methyl methacrylate solution, placed in a conical flask and heated in a water bath at 75 °C for 20 min, then the heating was stopped, and the conical flask was placed in cold water to cool to terminate the reaction.

[0064] (5) Preparation of bone cement: Using 2 g of methyl methacrylate prepolymer solution as the liquid phase, and a mixture of 100 mg of perfluorinated modified hydroxyapatite (HA-PFOM), 100 mg of alendronate sodium (ALN) and 10 mg of benzoyl peroxide (BPO) as the solid phase, and after adding 10 mg of N,N-dimethylaniline (DMA), the two phases were thoroughly mixed and injected into a mold. It was placed in an oven at 37 °C for heating and curing, and the final bone cement sample was obtained after demolding.

[0065] Example 2

[0066] The preparation method of an injectable bone cement with low exotherm and low elastic modulus in this example is different from that in Example 1. In this example, a mixture of 200 mg of perfluorinated modified hydroxyapatite (HA-PFOM), 200 mg of alendronate sodium (ALN) and 10 mg of benzoyl peroxide (BPO) was used as the solid phase.

[0067] Example 3

[0068] The preparation method of an injectable bone cement with low exotherm and low elastic modulus in this example is different from that in Example 1. In this example, 300 mg of perfluorinated modified hydroxyapatite (HA-PFOM), 300 mg of alendronate sodium (ALN), and 10 mg of benzoyl peroxide (BPO) are mixed as the solid phase.

[0069] Example 4

[0070] The preparation method of an injectable bone cement with low exotherm and low elastic modulus in this example is different from that in Example 1. In this example, 400 mg of perfluorinated modified hydroxyapatite (HA-PFOM), 400 mg of alendronate sodium (ALN), and 10 mg of benzoyl peroxide (BPO) are mixed as the solid phase.

[0071] The contents of perfluorinated modified hydroxyapatite and alendronate sodium in Examples 1-4 are shown in the following table:

[0072] Table 1 Contents of perfluorinated modified hydroxyapatite and alendronate sodium in Examples 1-4

[0073]

[0074] As Figure 8 shown, the maximum temperature during the polymerization process is lower than 43 °C, far lower than the requirement of less than 90 °C in the international standard of surgical implants - acrylic resin cement (ISO-5833), which can inhibit tissue damage caused by a large amount of heat release during the polymerization process.

[0075] As Figure 9 shown, according to the method in the international standard of surgical implants - acrylic resin cement (ISO-5833), the setting times of the 4 groups of bone cements are measured to be 10-14 min, all meeting the requirement of less than 15 min in the national standard ISO-5833.

[0076] As Figure 10 shown, the bone cement splines are all cylinders with a diameter of 6 mm and a height of 12 mm. According to the test requirements in the international standard of surgical implants - acrylic resin cement (ISO-5833), the four groups of bone cements all meet the requirement of greater than 70 MPa in the national standard ISO-5833, maintaining good compressive mechanical properties.

[0077] As Figure 11As shown, the bone cement splines are all cylinders with a diameter of 6 mm and a height of 12 mm. The elastic modulus measured on a universal material testing machine is between 700 MPa and 900 MPa, which is significantly lower than that of the usual PMMA bone cement (1700 MPa - 3700 MPa). To a certain extent, it can reduce the wear of normal bones and the risk of secondary fractures caused by the stress changes in the fractured vertebrae and adjacent vertebrae due to the high elastic modulus.

[0078] As Figure 12 shown, the bone cement splines are all cuboids with a length of 75 mm, a width of 10 mm, and a height of 3.3 mm. According to the method in the international standard of surgical implants - acrylic resin cement (ISO - 5833), the flexural strength of the four groups all meets the requirement of being greater than 50 MPa in the national standard ISO - 5833, indicating good flexural mechanical properties.

[0079] As Figure 13 shown, the results show that the bone cement has good injectability.

[0080] As Figure 14 shown, after soaking the bone cement blocks with a diameter of 6 mm and a height of 12 mm in porcine plasma for 7 days, the weight loss rates of each group are very low, indicating that it can still maintain the structural integrity and has good anti - dispersion ability.

[0081] As Figure 14 shown, after the bone cement particles are soaked in an aqueous solution for different times, the extract is mixed with ninhydrin and sodium bicarbonate solution, and after heating at 90 °C for 25 min, the release rate of alendronate sodium is calculated to increase with time through the change of the absorption peak at 570 nm in the ultraviolet - visible absorption spectrum, and the final release rate can reach about 64% after 7 days.

[0082] Cytotoxicity detection tests were carried out on the bone cements of Examples 1 - 4 and the control group. That is, the bone cement powder was soaked in deionized water for 24 h, and the supernatant was extracted and incubated with bone marrow macrophages in a 96 - well plate for 24 h. Then, CCK - 8 reagent was added to each well and incubated at 37 °C for 2 h, and the ultraviolet - visible absorbance at 450 nm was measured.

[0083] Table 2 Results of cytotoxicity detection tests for the bone cements of Examples 1 - 4 and the control group

[0084] Experimental group Survival rate of bone marrow macrophages Control group 100％ Example 1 99.7％ Example 2 98.3％ Example 3 97.7％ Example 4 97.2％

[0085] As can be seen from Table 2, the calculated cell survival rates are all above 97%, proving that the bone cements prepared in Examples 1 - 4 of the present invention have good biocompatibility.

[0086] The alkaline phosphatase (ALP) activities of the bone cements in Examples 1-4 and the control group were measured. SD rat osteoblasts were seeded on a 24-well plate and co-cultured with the bone cements. Alkaline phosphatase (ALP) was extracted on the 7th day, and the absorbance at 409 nm was read using a plate reader. The ALP activity was normalized with the total protein content.

[0087] Table 3 Alkaline phosphatase activity chart of the bone cements in Examples 1-4 and the control group

[0088] Experimental group Alkaline phosphatase activity Control group 4.1 Example 1 5.6 Example 2 6.4 Example 3 7.9 Example 4 11.7

[0089] As can be seen from Table 3, with the increase in the contents of alendronate sodium and modified hydroxyapatite, the alkaline phosphatase (ALN) activity increased significantly, which was beneficial to bone healing.

[0090] The above content is only an example and illustration of the structure of the present invention. Those skilled in the art of the present technology can make various modifications or supplements to the described specific embodiments or use similar methods for substitution. As long as they do not deviate from the structure of the present invention or exceed the scope defined by this claims, they should fall within the protection scope of the present invention.

Claims

1. A preparation method of an injectable bone cement with low heat release and low elastic modulus, characterized in that, It includes the following steps: (1) Double-bond modification of hydroxyapatite powder: Hydroxyapatite, hexamethylene diisocyanate and dibutyltin dilaurate are dissolved in anhydrous N,N-dimethylformamide, heated under reflux condensation and nitrogen protection. An appropriate amount of 2-hydroxyethyl methacrylate is dissolved in N,N-dimethylformamide and slowly injected into the above system. After stirring, it is centrifuged, washed multiple times with dichloromethane and the powder is collected, dried thoroughly, and ground and crushed with a mortar to obtain double bond-modified hydroxyapatite, and its structural formula is: (2) The double bond-modified hydroxyapatite powder is connected with a perfluorinated monomer through free radical polymerization to obtain perfluorinated modified hydroxyapatite; wherein, the preparation method of the perfluorinated monomer comprises the following steps: perfluorononanol, isocyanatoethyl methacrylate and triethylamine are dissolved in anhydrous tetrahydrofuran, heated and stirred, and tetrahydrofuran is removed by vacuum rotary evaporation to obtain a crude product. A mixed solution of petroleum ether and ethyl acetate is used as an eluent, and after purification by silica gel column chromatography and drying, a perfluorinated monomer is obtained, and its structural formula is as follows: (3) The perfluorinated modified hydroxyapatite, alendronate sodium and benzoyl peroxide are mixed as a solid phase and added to a liquid phase poly(methyl methacrylate) prepolymer. After being fully stirred and dispersed, N,N-dimethylaniline is added and stirred and dispersed again, and it is cured at a simulated human body temperature to obtain an injectable bone cement with low exotherm and low elastic modulus.

2. The preparation method of an injectable bone cement with low heat release and low elastic modulus according to claim 1, wherein: The molar ratio of the hydroxyapatite, hexamethylene diisocyanate, and 2-hydroxyethyl methacrylate is 1:1 - 3:3 - 10. The reaction temperature during the whole reaction process is 40 - 70 °C, the heating time under the conditions of condensation reflux and nitrogen protection is 6 - 18 h, the drying temperature is 35 - 50 °C, and the drying time is 12 - 36 h.

3. The preparation method of an injectable bone cement with low heat release and low elastic modulus according to claim 1, characterized in that, The specific steps of step (2) are as follows: Dissolve the double-bond modified hydroxyapatite, perfluorinated monomer, and azobisisobutyronitrile in anhydrous N,N-dimethylformamide and put them into a sealed tube. Freeze and degas three times under nitrogen, and then perform flame sealing under vacuum. Place it in an oil bath to react for a sufficient time and then cool to terminate the reaction. Wash it with dichloromethane multiple times and collect the powder. Dry it thoroughly, and grind and crush it with a mortar to obtain perfluorinated modified hydroxyapatite. Its structural formula is: 。 4. The preparation method of an injectable bone cement with low exotherm and low elastic modulus according to claim 1, wherein: During the preparation process of the perfluorinated modified hydroxyapatite, the molar ratio of the double-bond modified hydroxyapatite, perfluorinated monomer, and azobisisobutyronitrile is 1:3 - 10:0.1 - 0.5, the reaction temperature is 65 - 85 °C, the reaction time is 48 - 72 h, the drying temperature is 30 - 50 °C, and the freezing temperature is -50 - -80 °C; During the preparation process of the perfluorinated monomer, the molar ratio of perfluorononyl alcohol and ethyl α-cyanoacrylate is 1:1 - 5, the reaction temperature is 40 - 60 °C, the reaction time is 12 - 36 h, the volume ratio of petroleum ether and ethyl acetate is 6:1, the drying temperature is 35 - 45 °C, and the drying time is 8 - 16 h.

5. The preparation method of an injectable bone cement with low heat release and low elastic modulus according to claim 1, characterized in that, The specific steps of step (3) are as follows: Use methyl methacrylate prepolymer solution as the liquid phase, and use a mixture of perfluorinated modified hydroxyapatite, alendronate sodium, and benzoyl peroxide as the solid phase. After adding an appropriate amount of N,N-dimethylaniline, mix the two phases evenly and then heat and cure to obtain the injectable bone cement with low exotherm and low elastic modulus. Among them, the preparation method of the methyl methacrylate prepolymer solution is as follows: Heat the methyl methacrylate solution dissolved with the initiator in a water bath for a certain time, then stop heating and cool it in cold water to terminate the reaction.

6. The preparation method of an injectable bone cement with low exotherm and low elastic modulus according to claim 5, wherein: The mass ratio of the liquid phase to the solid phase is 1:0.05 - 0.

5. In the solid phase, the mass ratio of the perfluorinated modified hydroxyapatite to the alendronate sodium is 1:0.5 - 3, the mass of benzoyl peroxide is 0.2% - 3% of the mass of the methyl methacrylate prepolymer solution, the mass of N,N-dimethylaniline is 1% - 3% of the mass of the methyl methacrylate prepolymer solution, the heat curing temperature is 36 - 37 °C, and the curing time is 15 - 60 min; The initiator is benzoyl peroxide or azobisisobutyronitrile, the water bath heating temperature is 70 - 90 °C, and the mass of the initiator is 0.5% - 2.5% of the mass of the polymethyl methacrylate prepolymer solution.

7. An injectable bone cement with low heat release and low elastic modulus prepared by the preparation method of the injectable bone cement with low heat release and low elastic modulus according to any one of claims 1-6.

8. Use of the injectable bone cement with low heat release and low elastic modulus according to claim 7 in the preparation of an implant material for treating osteoporotic fractures.

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