A bone cement material, its preparation and use

Abstract

The application relates to a bone cement material and a preparation method and application thereof, and belongs to the technical field of bone tumor treatment medical devices. The preparation method comprises the following steps: 1) preparing a hydroxyapatite suspension liquid and mixing with an adriamycin diluent, adding ammonia water to adjust the pH value to be not less than 8.5, stirring uniformly after adding an adhesive to obtain component A; 2) preparing a coupling reaction of 4-bromomethyl phenyl boronic acid and a third-generation polyamidoamine dendritic polymer to obtain G3-PBA, adding quercetin into the G3-PBA solution, and obtaining component B after ultrasonic dissolution; and 3) preparing calcium phosphate powder, mixing with component B, stirring uniformly, and then manually stirring uniformly after adding component A to obtain the bone cement material. The quercetin in the bone cement material can be quickly released, effectively antibacterial, and conducive to early bone healing by regulating immunity, and the adriamycin can be long-acting released and has no long-term residue, so that the bone cement material also has a long-acting bone tumor treatment effect.

Description

Technical Field

[0001] This application relates to a bone cement material, its preparation method, and its application, belonging to the field of medical device technology for bone tumor treatment. Background Technology

[0002] Primary bone tumors are common malignant tumors in clinical practice, with a high incidence and poor prognosis in children. They are characterized by local destruction and high metastasis. The bone is also a common site of metastasis for malignant tumors, and bone tumors or bone metastases often cause bone defects. Therefore, implanting excellent filling materials to repair bone defects and restore bone mechanical properties is crucial. Bone cement, with its excellent biocompatibility, plasticity, and curing ability, is widely used in clinical practice.

[0003] Currently, the two main types of traditional bone cement commonly used in clinical practice are polymethyl methacrylate (PMMA) bone cement and calcium phosphate cement (CPC). CPC is primarily a bone cement formed from calcium phosphate salts, and its composition is similar to that of human bone tissue. It has good biocompatibility and a certain degree of biodegradability, and can organically integrate with the bone tissue interface. However, CPC suffers from low mechanical strength and poor osteogenic properties, making it prone to disintegration within the bone. Furthermore, both traditional CPC and PMMA bone cement lack effective anti-tumor functions and cannot effectively inhibit the in situ recurrence and distant metastasis of bone tumors.

[0004] Current research focuses on modifying bone cement to impart anti-tumor functions through drug loading and doping with particles possessing magnetothermal or photothermal properties, constructing novel multifunctional bone cements that can synergistically anti-tumor effects while filling defects, repairing and reconstructing bone tissue. Among these, magnetothermal and photothermal anti-tumor bone cements require external intervention, such as applying magnetic fields, to generate heat energy to assist tumor treatment, thus their clinical application remains in the research stage. Currently, the most widely used anti-tumor bone cements are based on traditional chemotherapy drugs, with adriamycin (DOX) being a commonly used chemotherapy drug.

[0005] Antitumor bone cement addresses different needs compared to ordinary bone cement. Firstly, all bone cement materials must consider infection control, as infection can be catastrophic. While the anti-infective components in bone cement cannot completely replace systemic medication during treatment, systemic antibiotics have limited effectiveness in eradicating local bone infections and suffer from drawbacks such as low local concentrations, susceptibility to drug-resistant bacteria, and significant systemic adverse reactions. In contrast, implanted antibacterial components in bone cement offer better targeted release, thus playing a crucial role in preventing infection at the surgical site. However, the use of antibacterial components requires careful control of release within a fixed treatment course. Targeted release helps avoid drug resistance caused by unstable release levels, while also reducing side effects and adverse reactions. On the other hand, there is the issue of chemotherapy drug release. Ideally, chemotherapy drugs should be released continuously during 1-2 months of chemotherapy treatment to achieve targeted and efficient drug delivery. However, if residual chemotherapy drugs require a longer period of time to be completely released, it will affect the bone healing process in the later stages of surgery. Furthermore, the host immune response and anti-infection are key factors in determining the success or failure of biomaterials in repairing bone defects, and the immune system plays a vital role in tumor treatment, defense against bone infection, and maintenance of bone homeostasis.

[0006] The species of microorganisms causing bone and joint infections vary across different regions and populations. Previously, Staphylococcus aureus was the most common cause of bone and joint infections. However, in recent years, with the widespread use of antibiotics targeting Staphylococcus aureus in orthopedic surgery, infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have shown an increasing trend. A multicenter retrospective study indicated that methicillin-sensitive Staphylococcus aureus remains the most common single pathogen causing traumatic bone infections. However, with the clinical implementation of targeted prophylaxis against Gram-positive bacteria, Gram-negative bacteria have become the main pathogens causing traumatic bone infections, with Pseudomonas aeruginosa being the predominant species.

[0007] Existing anti-tumor bone cement technologies still have room for improvement in terms of antibacterial and anti-tumor effects, and chemotherapy drugs have adverse effects on postoperative bone healing. Therefore, providing a novel multifunctional anti-tumor bone cement would have great clinical significance for the treatment of bone tumors. Summary of the Invention

[0008] To address the aforementioned issues, this application provides a bone cement material, its preparation method, and its application. The bone cement material prepared by this method contains quercetin encapsulated in G3-PBA, which can be rapidly released in the body. Doxorubicin, combined with hydroxyapatite and a binder, achieves long-term release. The pores formed by the rapidly released quercetin ensure that doxorubicin does not remain for long periods. Furthermore, the added quercetin, while effectively antibacterial, also plays an immunomodulatory role, promoting M2 polarization of macrophages and exhibiting anti-inflammatory effects, thus facilitating early bone healing after surgery. Combined with the long-term release of doxorubicin, this achieves a sustained therapeutic effect for bone tumors.

[0009] This application provides a method for preparing a bone cement material, the method comprising the following steps:

[0010] 1) Prepare a mixture of hydroxyapatite suspension and doxorubicin dilution, adjust the pH to not less than 8.5 with ammonia, add binder and stir evenly to obtain component A;

[0011] 2) Prepare 4-bromomethylphenylboronic acid and a third-generation polyamide-amine dendritic polymer for coupling reaction to obtain G3-PBA. Add quercetin to the G3-PBA solution and dissolve it by sonication to obtain component B.

[0012] 3) Prepare calcium phosphate powder and mix it with component B and stir evenly. Then add component A and stir evenly by hand to obtain the bone cement material.

[0013] In this application, quercetin is encapsulated with G3-PBA. Quercetin not only has a good antibacterial effect, but also has immunomodulatory function, which can promote M2 polarization of macrophages. The two main problems faced in the early stage of surgery are infection and the inflammatory response after implantation of foreign bodies, which affects bone healing. Quercetin can have a good antibacterial effect while reducing inflammation. Combined with the systemic antibiotics commonly used in clinical practice, it can effectively fight bacteria at the surgical site and promote rapid postoperative recovery and healing.

[0014] Quercetin encapsulated in G3-PBA dissolves well in the body and can be released stably in a short time, thus targeting bacterial membranes for rapid antibacterial action and reducing the risk of drug resistance due to unstable release. Furthermore, the material has a large molecular weight and spatial structure, allowing it to form larger pores within the bone cement after release. Its excellent release properties also facilitate the release of doxorubicin, preventing doxorubicin residues. This superior release also avoids quercetin's ability to promote macrophage M2 polarization, which could negatively impact the therapeutic efficacy of doxorubicin in tumor treatment.

[0015] Doxorubicin needs to achieve long-term release and be compatible with the entire radiotherapy course. At the same time, it also needs to be released stably and not easily leave long-term residues. Therefore, this plan uses doxorubicin in combination with an adhesive. When used with hydroxyapatite, it has a good adhesion effect to maintain long-term release. The large pores produced by the dissolution of quercetin are conducive to the stability and complete release of doxorubicin, and it is not easy to leave long-term residues, which would affect postoperative bone healing.

[0016] G3-PBA contains 4-bromomethylphenylboronic acid and a third-generation polyamide-amine dendritic polymer. The third-generation polyamide-amine dendritic polymer has a large spatial structure, and its internal hydrophobic cavities can effectively encapsulate quercetin. Quercetin can also be bound to the surface of G3-PBA through borate ester bonds. Together with 4-bromomethylphenylboronic acid, component B has good in vivo solubility and can form large pores inside the bone cement after dissolution.

[0017] During the preparation process, step 1) adjusting the pH to no less than 8.5 with ammonia water helps maintain the stability of doxorubicin and facilitates the adhesion of doxorubicin to magnesium phosphate and hydroxyapatite. In step 3), adding component A and then manually stirring it is more conducive to the stable release of doxorubicin and reduces the occurrence of its long-term residue.

[0018] Optionally, in step 3), when preparing calcium phosphate powder and mixing it with component B and stirring it evenly, 4-bromomethylphenylboronic acid coupled with carboxymethyl chitosan is also added.

[0019] 4-Bromomethylphenylboronic acid coupled with carboxymethyl chitosan has a large spatial structure, and carboxymethyl chitosan has good in vivo solubility. 4-Bromomethylphenylboronic acid further increases the molecular spatial volume while improving its solubility. Therefore, in this application, by adding 4-bromomethylphenylboronic acid coupled with carboxymethyl chitosan, large pores can be formed after dissolution, which can further improve the problem of long-term doxorubicin residue and avoid the adverse effects of prolonged doxorubicin residue on postoperative bone healing.

[0020] Optionally, the 4-bromomethylphenylboronic acid coupled carboxymethyl chitosan is synthesized by a Michael reaction of 4-bromomethylphenylboronic acid and carboxymethyl chitosan with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride as a coupling agent.

[0021] Optionally, the binder in step 1) is magnesium phosphate. When magnesium phosphate is used as a binder in combination with hydroxyapatite, it can achieve a good binding effect with doxorubicin. By adding magnesium phosphate in combination with calcium phosphate, a sustained-release effect of doxorubicin can be achieved. Moreover, magnesium phosphate has good in vivo solubility and compatibility. Therefore, while achieving long-term release of doxorubicin, it can reduce doxorubicin residue and stably release doxorubicin.

[0022] Optionally, the calcium phosphate is one or more of tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate, and calcium dihydrogen phosphate.

[0023] Optionally, the calcium phosphate is β-tricalcium phosphate. Because the rapid release of quercetin easily creates large pores in bone cement, and β-tricalcium phosphate, when used in combination with hydroxyapatite, exhibits better material strength, meeting the requirements for bone cement use. However, it should be noted that those skilled in the art can add other reinforcing agents during the preparation process to further improve the strength properties of the bone cement material.

[0024] Optionally, in step 3), the mass ratio of calcium phosphate powder to component A is 1:(0.4~0.8). When the mass ratio of calcium phosphate powder to component A is within this range, it provides good material strength while also better balancing the requirements of long-acting release of doxorubicin and avoiding prolonged residue.

[0025] Optionally, in step 3), when preparing calcium phosphate powder and mixing it with component B and stirring it evenly, the mixture should be stirred at a speed of not less than 200 rpm for at least 10 minutes.

[0026] When adding component A and stirring manually until homogeneous, stir manually at a speed not exceeding 60 rpm for 1 to 3 minutes.

[0027] When calcium phosphate powder is mixed with component B, it can improve the uniformity of quercetin distribution and reduce the generation of bubbles, which is more conducive to improving the strength of the material and the uniform release of quercetin. The more uniform pores after release are conducive to the long-term stable release of doxorubicin and reduce the occurrence of long-term residues.

[0028] When adding component A, manual stirring is used to ensure uniform mixing, which is more conducive to the release of doxorubicin and thus reduces the occurrence of its long-term residue.

[0029] This application provides bone cement materials prepared by the above-described method for preparing bone cement materials.

[0030] This application provides the use of the aforementioned bone cement material in the preparation of bone tumor treatment devices.

[0031] The beneficial effects of this application include, but are not limited to:

[0032] The bone cement material prepared by the method of this application includes quercetin encapsulated by G3-PBA, which can be rapidly released in the body environment. The combination of doxorubicin and hydroxyapatite as a binder can achieve long-term release. The pores formed by the rapidly released quercetin can ensure complete release of doxorubicin and prevent it from remaining for a long time.

[0033] The added quercetin not only provides effective antibacterial protection post-surgery but also plays an immunomodulatory role, promoting M2 polarization of macrophages and exerting an anti-inflammatory effect in the early postoperative period, which is more conducive to postoperative bone healing. Combined with the long-acting release of doxorubicin post-surgery, it can achieve better therapeutic effects for bone tumors. The G3-PBA-encapsulated quercetin can reduce its adverse reactions, and the rapid and stable release of quercetin can effectively target bacterial membranes, reducing the occurrence of drug resistance. After complete release, the disappearance of the M2 polarization regulation of macrophages will not affect the subsequent anti-tumor effect of doxorubicin. Furthermore, the large pores created after its release are more conducive to the stable release of doxorubicin and are less likely to cause long-term doxorubicin residue, avoiding adverse effects of doxorubicin on postoperative bone healing. Magnesium phosphate, as a binder, enables the long-acting release of doxorubicin, which can meet the requirements of stable and efficient complete release of doxorubicin throughout the entire chemotherapy course. Attached Figure Description

[0034] The accompanying drawings, which are included to provide a further understanding of this application and form part of this application, illustrate exemplary embodiments of this application and are used to explain this application, but do not constitute an undue limitation of this application. In the drawings:

[0035] Figure 1 For the G3-PBA involved in Embodiment 2 of this application 1 Figure of H NMR analysis results;

[0036] Figure 2 For the CMCS-PBA involved in Embodiment 3 of this application 1 Figure of H NMR analysis results;

[0037] Figure 3 This is a graph showing the cumulative release of quercetin in Test Example 1 of this application.

[0038] Figure 4 This is a graph showing the cumulative release of doxorubicin in Test Example 1 of this application;

[0039] Figure 5 This is a diagram illustrating the antibacterial effect of quercetin in Test Example 2 of this application;

[0040] Figure 6 This is a graph showing the positive ratio of CD68 and CD206 on the surface of macrophages involved in test example 3 of this application;

[0041] Figure 7 This is a graph showing the synergistic antitumor results of doxorubicin and quercetin involved in Test Example 4 of this application. Detailed Implementation

[0042] The present application is described in detail below with reference to the embodiments, but the present application is not limited to these embodiments. Unless otherwise specified, the raw materials and reagents in the embodiments of the present application are all purchased through commercial channels.

[0043] Example 1: Preparation of Component A

[0044] 1) Weigh 0.50 g of hydroxyapatite powder into a 100 mL glass beaker, add 20 mL of deionized water, and use an ultrasonic cleaner to sonicate for 15 min to fully disperse the nano-sized particles and form a uniform suspension. Keep the liquid temperature below 40℃.

[0045] 2) Weigh 5.0 mg of doxorubicin hydrochloride, dissolve it in 5 mL of deionized water, and mix it repeatedly by pipetting with a micropipette to form a 1 mg / mL doxorubicin dilution. Store it in the dark for later use.

[0046] 3) Mix the prepared suspension with the doxorubicin dilution while stirring to ensure thorough mixing, and continue stirring for 5 minutes;

[0047] 4) Use a calibrated pH meter to monitor the pH of the mixture, slowly add ammonia water dropwise while stirring, until the pH stabilizes between 8.5 and 9.0;

[0048] 5) Prepare 2 mL of 10 wt% magnesium phosphate aqueous solution and add it to the above mixed suspension. Continue stirring for 15 minutes to evenly distribute hydroxide ions and promote the adsorption of doxorubicin.

[0049] 6) Complete the preparation of component A;

[0050] It should be noted that the above operations should be performed under aseptic conditions and in the dark.

[0051] Example 2 Preparation of component B

[0052] 1) Weigh 400 mg of PAMAM-G3 and dissolve it in 10 mL of methanol, then add 300 mg of 4-bromomethylphenylboronic acid (PBA) and stir at 50 °C for 36 h;

[0053] 2) The reaction mixture was dialyzed in distilled water to obtain purified G3-PBA;

[0054] 3) Conduct 1 1H NMR analysis was used to characterize the purified G3-PBA, and the results are as follows: Figure 1 As shown;

[0055] 4) Take 300mg G3-PBA and add it to 5ml of water. Then add 10mg of quercetin to the solution and sonicate at 150W and 12kHz for 30 minutes until the quercetin is completely dissolved. This completes the preparation of component B.

[0056] Example 3: Preparation of 4-bromomethylphenylboronic acid coupled with carboxymethyl chitosan

[0057] 1) Dissolve 1 g of carboxymethyl chitosan (CMCS) in MES buffer (pH 5.5) under magnetic stirring;

[0058] 2) Dissolve 1.1 g of 4-carboxyphenylboronic acid (PBA) and 2.6 g of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholine chloride (DMTMM) in MES buffer (pH 5.5), and slowly add it dropwise to the solution in step 1), then keep the reaction at room temperature for 24 hours;

[0059] 3) The product was dialyzed with sodium chloride solution and distilled water, and then freeze-dried to remove water to obtain purified 4-bromomethylphenylboronic acid coupled carboxymethyl chitosan;

[0060] 4) Perform 1 ¹H NMR analysis was used to characterize the purified CMCS-PBA, and the results are as follows: Figure 2 As shown.

[0061] according to Figure 1 and Figure 2 As a result, new peaks corresponding to protons (7.0-7.8 ppm) in PBA were observed in the nuclear magnetic resonance spectra of G3-PBA and CMCS-PBA, confirming the successful synthesis of G3-PBA nanocarriers and CMCS-PBA polymers.

[0062] Example 4: Preparation of Bone Cement Material 1#

[0063] 1) Weigh 10 g of β-tricalcium phosphate powder (β-TCP) and place it in a clean, dry container;

[0064] 2) Weigh 3 g of component B;

[0065] 3) Slowly add β-tricalcium phosphate powder to component B. Use a high-speed stirrer with a paddle head, set the stirrer speed to 200 rpm, and stir continuously for at least 10 minutes to make the powder evenly wetted and dispersed.

[0066] 4) Weigh 6 g of component A and add it to the mixture stirred in the previous step;

[0067] 5) Use a manual stirring stick to stir evenly for 1 minute at a speed not exceeding 60 rpm. During the stirring process, you can use a spatula to scrape the sides intermittently to ensure that there is no dry powder residue.

[0068] 6) Complete the preparation of bone cement material #1.

[0069] Example 5: Preparation of Bone Cement Material #2

[0070] 1) Weigh 10 g of β-tricalcium phosphate powder (β-TCP) and place it in a clean, dry container;

[0071] 2) Weigh 3 g of component B;

[0072] 3) Weigh 0.1 g of 4-bromomethylphenylboronic acid coupled with carboxymethyl chitosan;

[0073] 4) Slowly add β-tricalcium phosphate powder and 4-bromomethylphenylboronic acid coupled carboxymethyl chitosan to component B. Use a high-speed stirrer with a paddle head, set the stirrer speed to 200 rpm, and stir continuously for at least 10 minutes to make the powder evenly wetted and dispersed.

[0074] 5) Weigh 6 g of component A and add it to the mixture stirred in the previous step;

[0075] 6) Use a manual stirring stick to stir evenly for 1 minute at a speed not exceeding 60 rpm. During the stirring process, you can use a spatula to scrape the sides intermittently to ensure that there is no dry powder residue.

[0076] 7) Complete the preparation of bone cement material #2.

[0077] Test Example 1: Release Results of Quercetin and Doxorubicin

[0078] Bone cement materials #1 and #2 were immersed in 10 mL of simulated body fluid SBF buffer for degradation experiments. The contents of quercetin and doxorubicin in the buffer were determined by high-performance liquid chromatography (HPLC). The chromatographic column was a Diamonsil C18 (4.6 × 250 mm). For the detection of quercetin, the mobile phase was methanol-0.025% phosphoric acid (60:40); the flow rate was 1 ml / min; the column temperature was 35℃; and the detection wavelength was 360 nm. Quercetin showed good linearity in the range of 0.182–0.889 μg, with a recovery rate of 97.42%. For the detection of doxorubicin, the mobile phase was acetonitrile-methanol-water (32:50:18); the flow rate was 1 ml / min; the column temperature was 35℃; and the detection wavelength was 560 nm. Doxorubicin showed good linearity in the range of 0.032–0.955 μg, with a recovery rate of 98.21%. The cumulative release of quercetin and doxorubicin at different time points was calculated based on the measured content, and the results are as follows: Figure 3 and Figure 4 As shown.

[0079] according to Figure 3 The results showed that quercetin was released relatively stably within 7 days, and was released rapidly and completely in the last 7 days within 14 days. After 14 days, the release of quercetin was basically not observed.

[0080] according to Figure 4 The results showed that the release rate of doxorubicin gradually increased within 14 days. Bone cement material #1 maintained a relatively stable release rate within 50 days, and the cumulative release amount reached approximately 99.3% after 50 days. Considering measurement error, there was essentially no residue. Bone cement #2 maintained a relatively stable release rate within 30 days, and the cumulative release amount reached approximately 99.1% after 30 days, also with virtually no residue.

[0081] Test Example 2: Antibacterial Test Results of Quercetin Alone

[0082] The concentration of Staphylococcus aureus prepared was 1×10⁻⁶. 7 Bone cement material #2 was immersed in DMEM culture medium containing CFU / mL. The content of Staphylococcus aureus in the solution at different time points was detected by colony formation assay to confirm the antibacterial efficacy of quercetin. The results are as follows: Figure 5 As shown.

[0083] according to Figure 5 The results show that quercetin in bone cement material #2 can be effectively released and exert antibacterial effects.

[0084] Test Example 3: Immunomodulatory Test Results of Quercetin Alone

[0085] THP-1 cell lines were cultured in RPMI medium containing 10% FBS. PMA (induction concentration: 100 ng / mL) was added to induce differentiation into M0 macrophages, followed by the addition of IL-4 (induction concentration: 20 ng / mL) and IL-13 (induction concentration: 20 ng / mL) to induce differentiation into M2 macrophages. Cells were then treated with 10 / 20 μM quercetin, and the positive ratios of CD68 and CD206 on the macrophage surface were detected by flow cytometry. The results are as follows: Figure 6 As shown.

[0086] according to Figure 6 The results showed that as the concentration of quercetin increased, the positive rate of CD206 increased significantly, confirming that quercetin played an immunomodulatory role in promoting macrophage polarization towards M2.

[0087] Test Example 4: Test on the synergistic antitumor effect of quercetin and doxorubicin

[0088] MG-63 osteosarcoma cell line was cultured in DMEM medium containing 10% FBS and treated with 10 μM quercetin and 5 μM doxorubicin. Cell viability was assessed using CCK-8 assay at different time points, and the results are as follows: Figure 7 As shown.

[0089] according to Figure 7 The results showed that doxorubicin had a stronger anti-tumor effect, and the anti-tumor effect was significantly enhanced when doxorubicin was combined with quercetin.

[0090] The above description is merely an embodiment of this application, and the scope of protection of this application is not limited to these specific embodiments, but is determined by the claims of this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the technical concept and principles of this application should be included within the scope of protection of this application.

Claims

1. A method for preparing a bone cement material, characterized in that, The preparation method includes the following steps: 1) Prepare a mixture of hydroxyapatite suspension and doxorubicin dilution, adjust the pH to not less than 8.5 with ammonia, add binder and stir evenly to obtain component A; 2) Prepare 4-bromomethylphenylboronic acid and a third-generation polyamide-amine dendritic polymer for coupling reaction to obtain G3-PBA. Add quercetin to the G3-PBA solution and dissolve it by sonication to obtain component B. 3) Prepare calcium phosphate powder and mix it with component B and stir evenly. Then add component A and stir evenly by hand to obtain the bone cement material.

2. The method for preparing bone cement material according to claim 1, characterized in that, In step 3), when preparing calcium phosphate powder and mixing it with component B and stirring it evenly, 4-bromomethylphenylboronic acid coupled with carboxymethyl chitosan is also added.

3. The method for preparing bone cement material according to claim 2, characterized in that, The 4-bromomethylphenylboronic acid coupled carboxymethyl chitosan was synthesized by a Michael reaction of 4-bromomethylphenylboronic acid and carboxymethyl chitosan with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholine chloride as a coupling agent.

4. The method for preparing bone cement material according to claim 1, characterized in that, The adhesive used in step 1) is magnesium phosphate.

5. The method for preparing bone cement material according to claim 1, characterized in that, The calcium phosphate is one or more of tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate, and calcium dihydrogen phosphate.

6. The method for preparing bone cement material according to claim 5, characterized in that, The calcium phosphate is β-tricalcium phosphate.

7. The method for preparing bone cement material according to claim 1, characterized in that, In step 3), the mass ratio of calcium phosphate powder to component A is 1:(0.4~0.8).

8. The method for preparing bone cement material according to claim 1, characterized in that, In step 3), when preparing calcium phosphate powder and mixing it with component B and stirring it evenly, the stirring speed shall be not less than 200 rpm for at least 10 minutes. When adding component A obtained in step 1), manually stir at a speed not exceeding 60 rpm for 1 to 3 minutes until it is evenly mixed.

9. A bone cement material, characterized in that, The bone cement material is a bone cement material prepared by the preparation method of bone cement material as described in any one of claims 1 to 8.

10. The application of a bone cement material in the preparation of bone tumor treatment devices, characterized in that, The bone cement material is the bone cement material as described in claim 9.

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