Antibacterial bone cement, bone cement set and preparation method of bone cement set

Abstract

The invention belongs to the field of biomedical materials, and relates to antibacterial bone cement, the bone cement comprises a powder and a liquid, the powder comprises polyacrylate and an antibacterial developer, and the liquid comprises N, N-dimethyl-p-toluidine, hydroquinone and methyl methacrylate; the antibacterial developing agent is a barium sulfate / copper oxide compound, the invention further provides a preparation method of the antibacterial developing agent in the antibacterial bone cement, an antibacterial bone cement set and a preparation method of the antibacterial bone cement set, the bone cement is endowed with certain antibacterial property by changing the composition of the developing agent, the elasticity modulus of the bone cement is reduced, and the bone cement set is prepared. And secondary injury caused by too high modulus of the bone cement is prevented.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials, and in particular to an antibacterial bone cement, a bone cement kit, and a method for preparing the bone cement kit. Background Technology

[0002] Bone cement is a common name for bone cement, a medical material used in orthopedic surgery. PMMA bone cement is an injectable filler and adhesive material, originally used in prosthesis replacement surgery. Currently, it is widely used in orthopedic clinics, especially in spinal repair and joint reconstruction. PMMA bone cement has many advantages as a filler material in orthopedic surgery: good injectability; good adhesion, allowing it to bond well with bone and implanted devices; excellent mechanical strength; and rapid curing time. However, as an injectable material for human use, PMMA bone cement also has obvious drawbacks. Its elastic modulus is 4 to 40 times that of vertebral cancellous bone. This excessively high elastic modulus leads to excessive hardness of the vertebral body, causing stress concentration and potentially resulting in compression fractures of adjacent vertebrae. Furthermore, PMMA bone cement lacks antibacterial properties, making it prone to infection during surgery and causing secondary harm to the patient.

[0003] Conventional methods to enhance the antibacterial properties of bone cement involve introducing antibiotics or metal ion antibacterial agents, such as gentamicin sulfate or silver nanoparticles, into the bone cement. However, the direct addition of antibacterial agents to bone cement may result in uneven mixing. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides an antibacterial bone cement, a bone cement kit, and a method for preparing the bone cement kit. The invention introduces copper oxide antibacterial agent into the developing agent, which reduces the elastic modulus of the bone cement, preventing secondary damage caused by excessively high bone cement modulus. It also avoids the potential for uneven mixing when the antibacterial agent is directly added to the bone cement, thus solving the problems mentioned in the background section.

[0005] The present invention provides the following technical solution: The first aspect of the present invention is to provide an antibacterial bone cement, which comprises two parts: powder and liquid. The powder comprises polyacrylate and an antibacterial contrast agent, and the liquid comprises N,N-dimethyl-p-toluidine, hydroquinone and methyl methacrylate; the antibacterial contrast agent is a barium sulfate / copper oxide complex.

[0006] The solid-liquid ratio of the bone cement powder and liquid is (1-3) g: 1 mL; The bone cement powder is composed of the following raw materials by weight percentage: 60%~90% polyacrylate and 10%~40% antibacterial contrast agent; The liquid bone cement is composed of the following raw materials in the indicated mass percentages: N,N-dimethyl-p-toluidine 0.5%~5%, hydroquinone 0.05%~2%, and methyl methacrylate 93%~99.45%.

[0007] The antibacterial developing agent comprises copper oxide in a mass percentage of 10% to 50%, and barium sulfate in a mass percentage of 50% to 90%.

[0008] A second aspect of the present invention is to provide a method for preparing the antibacterial contrast agent in antibacterial bone cement as follows: (1) Prepare barium nitrate solution and copper nitrate solution of the same concentration from 0.02 mol / L to 0.34 mol / L; (2) Add the copper nitrate solution to the barium nitrate solution at a volume ratio of 50~95:5~50 and mix for 2h-24h to obtain a uniform barium nitrate copper mixture. (3) Prepare a 0.01%~0.65% (w / w) polyvinyl alcohol (PVA) aqueous solution, and then add sodium sulfate to prepare a 0.02 mol / L~0.34 mol / L sodium sulfate / polyvinyl alcohol solution; (4) Add the barium copper mixture to a sodium sulfate / polyvinyl alcohol solution of the same molar concentration. The volume ratio of the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution is 1:1~2.3. The addition rate is (12.5~62.5) mL / min. The mixing and stirring rate is (200~900) r / min. After the addition is complete, mix for (12~48) h to obtain a suspension. (5) Place the precipitate, remove the supernatant, dry it, and then transfer the precipitate to a sintering furnace. Heat it to (700~900)℃ at a heating rate of (7.0~35.0)℃ / min, keep it at that temperature for (2~6h), and then cool it naturally to room temperature to obtain barium sulfate / copper oxide antibacterial developer with a particle size distribution range of (2~108)μm.

[0009] An antibacterial contrast agent was prepared by emulsifying sodium sulfate and a mixture of barium copper nitrate of the same concentration via emulsion-chemical homogeneous precipitation. Polyvinyl alcohol (PVA) enhances the surface tension of the reaction solution, encapsulates and segments the reaction ions, slows down the reaction growth rate, controls the particle size of the reaction product, and prevents further growth of the precipitated particles, resulting in a homogeneous PVA-coated barium sulfate / copper sulfate product. The sulfate ions and the PVA particles are then removed by sintering to obtain a copper oxide / barium sulfate antibacterial contrast agent with controllable particle size and morphology. This is essentially PVA-coated barium copper sulfate; after sintering, the PVA burns away, and the copper sulfate dehydrates to become copper oxide, which adheres to the barium sulfate. Furthermore, the introduction of copper oxide as an antibacterial agent into the contrast agent reduces the elastic modulus of the bone cement, preventing secondary damage caused by excessively high bone cement modulus. The prepared barium sulfate / copper oxide antibacterial contrast agent has a particle size distribution range of 2–108 micrometers, exhibits good biocompatibility, has no potential cytotoxicity, and avoids the cytotoxicity caused by nano-antibacterial ions.

[0010] A third aspect of the present invention is to provide a bone cement kit comprising any of the aforementioned antibacterial bone cements, specifically an antibacterial bone cement kit comprising the bone cement and a sealing and protective device, wherein the sealing and protective device comprises a blister box, a transparent bowl, an ampoule, a protective cap, and a guide tube, the transparent bowl being the inner packaging of the powder, the ampoule being the inner packaging of the liquid with a protective cap on the upper part, the blister box being the middle packaging, and the transparent bowl, ampoule, protective cap, and guide tube being packaged together in the blister box.

[0011] The antibacterial bone cement kit includes a blister box containing a blister film and a transparent bowl containing a blister film. The upper end of the ampoule has N+1 first protrusions, where N>1. The lower end of the protective cap has N+1 second protrusions. The protective cap is detachably mounted on the ampoule. The upper end of the protective cap has an internal thread 32 structure for connecting the guide tube. The guide tube is a long, pointed cylindrical structure with a hollow middle section and an external thread structure at the lower end for connecting the protective cap. The guide tube contains a needle filter structure.

[0012] The needle filter structure includes a needle and a filter plate, and the filter plate is provided with filter plate holes.

[0013] The transparent bowl is made of polypropylene, the blister film is made of Tyvek, and the ampoule is made of borosilicate glass. The first protrusion has a spacing of (5-10) mm, a width of (2-4) mm, and a height of (2-5) mm. The protective cap is made of polypropylene. The second protrusion has a spacing of (5-10) mm, a width of (2-4) mm, and a height of (2-5) mm. The connection between the ampoule and the protective cap is such that the lower N rings of the protective cap coincide with the upper N rings of the first protrusion on the ampoule, where N > 1.

[0014] The filter plate in the guide tube has a hole diameter of (0.05~0.48) mm and a thickness of (1~5) mm. The upper end of the guide tube is a cylindrical structure with an outer diameter of (6-10) mm and an inner diameter of (4-6) mm. The blister box contains one bowl groove, one guide tube groove, and one ampoule bottle groove.

[0015] A fourth aspect of the present invention is to provide a method for preparing a bone cement kit using the antibacterial bone cement described in any one of the first inventions, specifically a method for preparing an antibacterial bone cement kit: (1) Mix a measured amount of polyacrylate with the antibacterial developer evenly, transfer to a transparent bowl, and seal with plastic; (2) Mix a measured amount of N,N-dimethyl-p-toluidine, hydroquinone, and methyl methacrylate evenly, pour the mixture into an ampoule, seal it with a flame-drawn seal, and install the protective cap onto the ampoule, with the first and second protrusions overlapping. (3) Place the transparent bowl, the ampoule with the protective cap, and the guide tube into the blister pack and seal it. (4) When using, open the blister pack, take out the transparent bowl, ampoule, and guide tube; (5) Connect the guide tube to the ampoule cap using a threaded connection; (6) Press down the protective cap and make it coincide with the first protrusion of the N+1 ring of the ampoule. The needle in the guide tube punctures the ampoule. (7) Open the transparent bowl and pour all the liquid in the ampoule into the powder in the transparent bowl through the guide tube. Filter out the glass shards with the filter plate. (8) Use the upper end of the guide tube to mix the bone cement for 15s~60s. After mixing evenly, the bone cement has an operation time of 5min~18min and a curing time of 15min~30min to complete the filling and fixation.

[0016] Compared with the prior art, the present invention has the following beneficial effects: An antibacterial contrast agent was prepared by emulsifying sodium sulfate and a mixture of barium copper nitrate of the same concentration via emulsion-chemical homogeneous precipitation. Polyvinyl alcohol (PVA) was used to enhance the surface tension of the reaction solution, encapsulate and segment the reaction ions, slow down the reaction growth rate, control the particle size of the reaction product, and prevent further growth of the precipitated particles, resulting in a homogeneous barium sulfate / copper sulfate product coated with PVA. The sulfate ions and the PVA particles coated with PVA were then removed by sintering, yielding a copper oxide / barium sulfate antibacterial contrast agent with controllable particle size and morphology. Furthermore, the introduction of copper oxide as an antibacterial agent into the contrast agent reduced the elastic modulus of the bone cement, preventing secondary damage caused by excessively high bone cement modulus.

[0017] This invention imparts certain antibacterial properties to bone cement by altering the composition of the developing agent, thereby reducing the elastic modulus of the bone cement and preventing secondary damage caused by excessively high bone cement modulus. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the three-dimensional structure of the transparent bowl in specific embodiment 1 of the present invention; Figure 2 This is a schematic diagram of the main structure of the transparent bowl in specific embodiment 1 of the present invention; Figure 3 This is a schematic diagram of the main structure of the ampoule in specific embodiment 1 of the present invention; Figure 4 This is a schematic diagram of the cross-sectional structure of ampoule AA according to a specific embodiment of the present invention; Figure 5 This is a schematic diagram of the three-dimensional cross-sectional structure of the ampoule in specific embodiment 1 of the present invention; Figure 6 This is a schematic diagram of the protective cap according to a specific embodiment 1 of the present invention; Figure 7 This is a schematic cross-sectional view of the protective cap BB in a specific embodiment 1 of the present invention; Figure 8 This is a schematic diagram of the three-dimensional cross-sectional structure of the protective cap in specific embodiment 1 of the present invention; Figure 9 This is a three-dimensional schematic diagram of the guide tube in a specific embodiment 1 of the present invention; Figure 10 This is a three-dimensional cross-sectional view of the guide tube in a specific embodiment 1 of the present invention; Figure 11 This is a test diagram of the bending properties of bone cement prepared in the antibacterial bone cement kit of specific embodiment 1 of the present invention; Figure 12 Specific embodiment 1 of the present invention: Staphylococcus aureus inhibitory effect of antibacterial bone cement; Figure 13 The relative cell viability test diagrams in specific embodiments 1, 3, 5, and 6 of this invention.

[0019] In the diagram: 1. Transparent bowl; 2. Ampoule; 21. First protrusion; 3. Protective cap; 31. Second protrusion; 32. Internal thread; 4. Guide tube; 41. External thread; 42. Needle; 43. Filter plate; 44. Filter plate hole. Detailed Implementation

[0020] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0021] Specific Implementation Example 1: Please refer to Figure 1-10Antibacterial bone cement kit, consisting of bone cement and sealing protection device, is mainly used as a fixation and repair material for fractures.

[0022] Bone cement consists of two parts: powder and liquid. The solid-liquid ratio of the bone cement powder to the liquid is 2g:1mL. The bone cement powder is composed of the following raw materials by mass percentage: 90% polyacrylate (containing BPO) and 10% antibacterial contrast agent. The bone cement liquid is composed of the following raw materials by mass percentage: 2% N,N-dimethyl-p-toluidine, 0.05% hydroquinone, and 97.95% methyl methacrylate. The antibacterial contrast agent is a 60% barium sulfate / 40% copper oxide complex. The preparation method of the antibacterial developing agent is as follows: (1) Prepare barium nitrate solution and copper nitrate solution of the same concentration (0.03 mol / L); (2) Add the copper nitrate solution to the barium nitrate solution at a volume ratio of 60:40 and mix for 24 hours to obtain a uniform barium nitrate copper mixture. (3) Prepare a 0.04% (w / w) aqueous solution of polyvinyl alcohol (PVA), and then add sodium sulfate to prepare a 0.03 mol / L sodium sulfate / polyvinyl alcohol solution; (4) Add the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution of the same molar concentration. The volume ratio of the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution is 1:1.5. The addition rate is 62.5 mL / min. The mixing and stirring rate is 600 r / min. After the addition is complete, mix for 24 h to obtain a suspension. (5) Place the precipitate, remove the supernatant, dry it, and then transfer the precipitate to a sintering furnace. Heat it to 700°C at a heating rate of 12°C / min, keep it at that temperature for 2 hours, and then let it cool naturally to room temperature to obtain barium sulfate / copper oxide antibacterial developer with a particle size distribution range of 5~83μm.

[0023] The preparation method of the bone cement kit is as follows: (1) Mix 90% by weight of polyacrylate (containing BPO) with 10% of antibacterial developer evenly, transfer to transparent bowl 1, and seal; (2) Mix 2% N,N-dimethyl-p-toluidine, 0.05% hydroquinone and 97.95% methyl methacrylate evenly, pour into ampoule 2, seal with flame drawing, install protective cap 3 on ampoule 2, N rings of the first protrusion 21 and the second protrusion 31 overlap, N=2; (3) Place the transparent bowl 1, the ampoule 2 with the protective cap 3 installed, and the guide tube 4 into the blister box and seal it; (4) When using, open the blister pack, take out the transparent bowl 1, ampoule 2 and guide tube 4; (5) Connect the guide tube 4 to the protective cap 3 of the ampoule 2 via a threaded structure; (6) Press down the protective cap 3 and the first protrusion 21 of the three rings of the ampoule 2 to overlap, and the needle 42 in the guide tube 4 punctures the ampoule 2; (7) Open the transparent bowl 1 and pour all the liquid in the ampoule 2 into the powder in the transparent bowl 1 through the guide tube 4. The filter plate 43 filters out the glass shards. (8) Use the upper pipe structure of the guide tube 4 to stir and mix the bone cement for 30 seconds. After mixing evenly, the bone cement has a 7-minute operation time and a 15-minute curing time to complete the filling and fixation.

[0024] In sealing protection devices, such as Figure 1 As shown, the transparent bowl 1 is made of PP material, with a bowl diameter of 88mm, a height of 34mm, and a wall thickness of 1.5mm. The blister film is made of Tyvek material. Figure 2 As shown, ampoule 2 is made of high borosilicate glass, with a height of 115mm, a body diameter of 22.5mm, and a wall thickness ≥0.5mm. The upper part of the ampoule has three concentric rings of first protrusions 21, spaced 5mm apart, with a width of 2mm and a height of 2mm. (See diagram for details.) Figure 3 As shown, the protective cap 3 is made of PP material, with a diameter of 23mm and a wall thickness of 0.4mm. It has three rings of second protrusions 31 at the lower end, spaced 5mm apart, with a width of 2mm and a height of 2mm. The upper end has an internal thread 32 structure for connecting the guide tube 4. The protective cap 3 is installed on the ampoule 2, with the lower two rings of second protrusions 31 of the protective cap 3 coinciding with the upper two rings of first protrusions 21 of the ampoule 2. This ensures a tight connection between the protective cap 3 and the ampoule 2, preventing slippage and protecting the ampoule head from breakage. Figure 4 As shown, the guide tube 4 is made of PP material, with a long pointed cylindrical structure, 130mm in length and a maximum diameter of 23.3mm. The lower end has an external thread 41 for connecting to the protective cap 3. It is equipped with a needle filter structure; the needle 42 is a cylindrical structure with a diameter of 2mm and a length of 10mm. The filter plate hole 44 has a diameter of 0.3mm and a thickness of 2mm. The upper end is a cylindrical tube structure with an outer diameter of 8mm and an inner diameter of 6mm. The blister box is made of PP material, 200mm long, 100mm wide, and 50mm high. The blister box contains one bowl slot, one guide tube slot, and one ampoule slot. The blister box wall thickness is 2mm.

[0025] In this invention, the powder and liquid are placed in the same inner packaging, with the powder inner packaging being a transparent bowl 1, which also serves as a mixing container, avoiding the risk of introducing external contaminants that may occur during bone cement powder transfer. Furthermore, unlike conventional protective caps 3 installed on the ampoule head, the ampoule 2 has a three-ringed protrusion design. The protrusions of the ampoule 2 and the protective cap overlap to protect the ampoule head from lateral forces, preventing breakage, and also protecting the ampoule head from breakage before use. During use, the needle-punched filter structure in the guide tube 4 changes the conventional method of breaking the neck of the ampoule 2 to pour out the liquid; instead, it punctures the ampoule head with a needle, preventing liquid splashing and spillage caused by the ampoule 2 swinging when broken, thus preventing personal injury. The filter plate 43 filters and traps glass fragments, further preventing accidental injury from glass residue. Simultaneously, the materials used are PP or PTFE and high borosilicate glass, all of which are inert to methyl methacrylate in the bone cement liquid and will not change or affect the composition or performance of the bone cement.

[0026] This invention imparts antibacterial properties to bone cement by altering the composition of the contrast agent. The main difference lies in the composition of the antibacterial contrast agent. Conventional methods to enhance the antibacterial properties of bone cement involve introducing antibiotics or metal ion antibacterial agents, such as gentamicin sulfate or silver nanoparticles. However, directly adding antibacterial agents to the cement can lead to uneven mixing. This invention utilizes a copper oxide / barium sulfate antibacterial contrast agent with controllable particle size and morphology. Simultaneously, the structure and material design of the sealing protective suit reduce the risk of infection for patients during bone cement surgery. It also lowers the elastic modulus of the bone cement, preventing secondary damage caused by excessively high modulus. The polyacrylate mentioned in this patent refers to a polyacrylate containing BPO, which is dibenzoyl peroxide, also known as initiator BPO. The polyacrylate in bone cement powder is generally a BPO-containing polyacrylate, as is known to those skilled in the art.

[0027] Antibacterial bone cement was formed into a cylindrical shape with a diameter of 6mm × 12mm, and its bending performance was tested. Figure 11 As shown, the flexural strength of the antibacterial bone cement is 62.42 MPa, which is consistent with that of ordinary bone cement using 10% barium sulfate as a contrast agent; however, the flexural modulus is 2577.08, which is significantly lower.

[0028] Antibacterial bone cement was made into Φ12mm×2mm discs and subjected to antibacterial experiments, as shown in the attached figure. Figure 12 As shown, the inhibition zone is clearly visible, indicating that the antibacterial bone cement has good antibacterial properties against Staphylococcus aureus.

[0029] Antibacterial bone cement was prepared into Φ12mm×2mm discs. An extract was prepared by adding 5mL of extraction medium (MEM medium containing serum) to 1g of the cement and incubating at 37±1℃ for 24±2 hours. The extract was then used to test the relative cell viability according to the extract test method specified in GB / T16886.5. Figure 13 As shown, the relative cell viability of the sample extract was 91.3%, with no potential cytotoxicity (greater than 70%), and good biocompatibility. Specific Implementation Example 2

[0030] Antibacterial bone cement kit, consisting of bone cement and a sealing protection device.

[0031] Bone cement consists of two parts: powder and liquid. The solid-liquid ratio of the bone cement powder to the liquid is 3g:1mL. The bone cement powder is composed of the following raw materials by mass percentage: 60% polyacrylate (containing BPO) and 40% antibacterial contrast agent. The bone cement liquid is composed of the following raw materials by mass percentage: 1% N,N-dimethyl-p-toluidine, 0.05% hydroquinone, and 98.95% methyl methacrylate. The antibacterial contrast agent is an 80% barium sulfate / 20% copper oxide complex. The preparation method of the antibacterial developing agent is as follows: (1) Prepare barium nitrate solution and copper nitrate solution of the same concentration (0.34 mol / L); (2) Add the copper nitrate solution to the barium nitrate solution at a volume ratio of 80:40 and mix for 24 hours to obtain a uniform barium nitrate copper mixture. (3) Prepare a 0.65% (w / w) aqueous solution of polyvinyl alcohol (PVA), and then add sodium sulfate to prepare a 0.03 mol / L sodium sulfate / polyvinyl alcohol solution; (4) Add the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution of the same molar concentration. The volume ratio of the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution is 1:2. The addition rate is 12.5 mL / min. The mixing and stirring rate is 900 r / min. After the addition is complete, mix for 24 h to obtain a suspension. (5) Place the precipitate, remove the supernatant, dry it, and then transfer the precipitate to a sintering furnace. Heat it to 800°C at a heating rate of 7°C / min, keep it at that temperature for 2 hours, and then let it cool naturally to room temperature to obtain barium sulfate / copper oxide antibacterial developer with a particle size distribution range of 2~108μm.

[0032] The preparation method of the bone cement kit is as follows: (1) Mix 60% by weight of polyacrylate (containing BPO) with 40% of antibacterial developer evenly, transfer to transparent bowl 1, and seal; (2) Mix 1% by mass of N,N-dimethyl-p-toluidine, 0.05% hydroquinone and 98.95% methyl methacrylate evenly, pour into ampoule 2, seal with flame drawing, install protective cap 3 on ampoule 2, and overlap the first protrusion 21 and the second protrusion 31. (3) Place the transparent bowl 1, the ampoule 2 with the protective cap 3 installed, and the guide tube 4 into the blister box and seal it; (4) When using, open the blister pack, take out the transparent bowl 1, ampoule 2 and guide tube 4; (5) Connect the guide tube 4 to the protective cap 3 of the ampoule 2 via a threaded structure; (6) Press down the protective cap 3 and the first protrusion 21 of the three rings of the ampoule 2 to overlap, and the needle 42 in the guide tube 4 punctures the ampoule 2; (7) Open the transparent bowl 1 and pour all the liquid in the ampoule 2 into the powder in the transparent bowl 1 through the guide tube 4. The filter plate 43 filters out the glass shards. (8) Use the upper pipe structure of the guide tube 4 to stir and mix the bone cement for 60 seconds. After mixing evenly, the bone cement has a 17-minute operation time and a 25-minute curing time to complete the filling and fixation. Specific Implementation Example 3

[0033] Antibacterial bone cement kit, consisting of bone cement and a sealing protection device.

[0034] Bone cement consists of two parts: powder and liquid. The solid-liquid ratio of the bone cement powder to the liquid is 2g:1mL. The bone cement powder is composed of the following raw materials by mass percentage: 70% polyacrylate (containing BPO) and 30% antibacterial contrast agent. The bone cement liquid is composed of the following raw materials by mass percentage: 1.2% N,N-dimethyl-p-toluidine, 0.05% hydroquinone, and 98.75% methyl methacrylate. The antibacterial contrast agent is a 70% barium sulfate / 30% copper oxide complex. The preparation method of the antibacterial developing agent is as follows: (1) Prepare barium nitrate solution and copper nitrate solution of the same concentration, both at 0.13 mol / L; (2) Add the copper nitrate solution to the barium nitrate solution at a volume ratio of 70:20 and mix for 24 hours to obtain a uniform barium copper nitrate mixture. (3) Prepare a 0.35% (w / w) aqueous solution of polyvinyl alcohol (PVA), and then add sodium sulfate to prepare a 0.13 mol / L sodium sulfate / polyvinyl alcohol solution; (4) Add the barium copper mixture to a sodium sulfate / polyvinyl alcohol solution of the same molar concentration. The volume ratio of the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution is 1:2.3. The addition rate is 25 mL / min, the mixing and stirring rate is 800 r / min, and the mixture is stirred for 24 h after the addition is completed to obtain a suspension. (5) Place the precipitate, remove the supernatant, dry it, and then transfer the precipitate to a sintering furnace. Heat it to 800°C at a heating rate of 20°C / min, keep it at that temperature for 2 hours, and then let it cool naturally to room temperature to obtain barium sulfate / copper oxide antibacterial developer with a particle size distribution range of 15~63μm.

[0035] The preparation method of the bone cement kit is as follows: (1) Mix 70% by weight of polyacrylate (containing BPO) with 30% of antibacterial developer evenly, transfer to transparent bowl 1, and seal; (2) Mix 1.2% by weight of N,N-dimethyl-p-toluidine, 0.05% hydroquinone and 98.75% methyl methacrylate evenly, pour into ampoule 2, seal with flame drawing, install protective cap 3 on ampoule 2, and overlap the first protrusion 21 and the second protrusion 31. (3) Place the transparent bowl 1, the ampoule 2 with the protective cap 3 installed, and the guide tube 4 into the blister box and seal it; (4) When using, open the blister pack, take out the transparent bowl 1, ampoule 2 and guide tube 4; (5) Connect the guide tube 4 to the protective cap 3 of the ampoule 2 via a threaded structure; (6) Press down the protective cap 3 and the first protrusion 21 of the three rings of the ampoule 2 to overlap, and the needle 42 in the guide tube 4 punctures the ampoule 2; (7) Open the transparent bowl 1 and pour all the liquid in the ampoule 2 into the powder in the transparent bowl 1 through the guide tube 4. The filter plate 43 filters out the glass shards. (8) Use the upper pipe structure of the guide tube 4 to stir and mix the bone cement for 60 seconds. After mixing evenly, the bone cement has a 15-minute operation time and a 20-minute curing time to complete the filling and fixation.

[0036] Antibacterial bone cement was prepared into Φ12mm×2mm discs. An extract was prepared by adding 5mL of extraction medium (MEM medium containing serum) to 1g of the cement and incubating at 37±1℃ for 24±2 hours. The extract was then used to test the relative cell viability according to the extract test method specified in GB / T16886.5. Figure 13 As shown, the relative cell viability of the sample extract was 82.0%, with no potential cytotoxicity (greater than 70%), and good biocompatibility. Specific Implementation Example 4

[0037] Antibacterial bone cement kit, consisting of bone cement and a sealing protection device.

[0038] Bone cement consists of two parts: powder and liquid. The solid-liquid ratio of the bone cement powder to the liquid is 2g:1mL. The bone cement powder is composed of the following raw materials by mass percentage: 68% polyacrylate and 32% antibacterial contrast agent. The bone cement liquid is composed of the following raw materials by mass percentage: 1.4% N,N-dimethyl-p-toluidine, 0.05% hydroquinone, and 98.55% methyl methacrylate. The antibacterial contrast agent is a 63% barium sulfate / 37% copper oxide complex. The preparation method of the antibacterial developing agent is as follows: (1) Prepare barium nitrate solution and copper nitrate solution of the same concentration (0.21 mol / L); (2) Add copper nitrate solution to barium nitrate solution at a volume ratio of 63:37 and mix for 24 hours to obtain a uniform barium nitrate copper nitrate mixture. (3) Prepare a 0.53% (w / w) aqueous solution of polyvinyl alcohol (PVA), and then add sodium sulfate to prepare a 0.21 mol / L sodium sulfate / polyvinyl alcohol solution; (4) Add the barium copper mixture to a sodium sulfate / polyvinyl alcohol solution of the same molar concentration. The volume ratio of the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution is 1:1.7. The addition rate is 41 mL / min. The mixing and stirring rate is 800 r / min. After the addition is complete, mix for 24 h to obtain a suspension. (5) Place the precipitate, remove the supernatant, dry it, and then transfer the precipitate to a sintering furnace. Heat it to 896°C at a heating rate of 28°C / min, keep it at that temperature for 2 hours, and then let it cool naturally to room temperature to obtain barium sulfate / copper oxide antibacterial developer with a particle size distribution range of 13~85μm.

[0039] The preparation method of the bone cement kit is as follows: (1) Mix 68% by weight of polyacrylate (containing BPO) with 32% of antibacterial developer evenly, transfer to transparent bowl 1, and seal; (2) Mix 1.4% by weight of N,N-dimethyl-p-toluidine, 0.05% hydroquinone and 98.55% methyl methacrylate evenly, pour into ampoule 2, seal with flame drawing, install protective cap 3 on ampoule 2, and overlap the first protrusion 21 and the second protrusion 31. (3) Place the transparent bowl 1, the ampoule 2 with the protective cap 3 installed, and the guide tube 4 into the blister box and seal it; (4) When using, open the blister pack, take out the transparent bowl 1, ampoule 2 and guide tube 4; (5) Connect the guide tube 4 to the protective cap 3 of the ampoule 2 via a threaded structure; (6) Press down the protective cap 3 and the first protrusion 21 of the three rings of the ampoule 2 to overlap, and the needle 42 in the guide tube 4 punctures the ampoule 2; (7) Open the transparent bowl 1 and pour all the liquid in the ampoule 2 into the powder in the transparent bowl 1 through the guide tube 4. The filter plate 43 filters out the glass shards. (8) Use the upper pipe structure of the guide tube 4 to stir and mix the bone cement for 60 seconds. After mixing evenly, the bone cement has a 13-minute operation time and a 18-minute curing time to complete the filling and fixation. Specific Implementation Example 5

[0040] Antibacterial bone cement kit, consisting of bone cement and a sealing protection device.

[0041] Bone cement consists of two parts: powder and liquid. The solid-liquid ratio of the bone cement powder to the liquid is 2g:1mL. The bone cement powder is composed of the following raw materials by mass percentage: 64% polyacrylate and 36% antibacterial contrast agent. The bone cement liquid is composed of the following raw materials by mass percentage: 1.5% N,N-dimethyl-p-toluidine, 0.05% hydroquinone, and 98.45% methyl methacrylate. The antibacterial contrast agent is a 90% barium sulfate / 10% copper oxide complex. The preparation method of the antibacterial developing agent is as follows: (1) Prepare barium nitrate solution and copper nitrate solution of the same concentration (0.29 mol / L); (2) Add the copper nitrate solution to the barium nitrate solution at a volume ratio of 90:10 and mix for 24 hours to obtain a uniform barium nitrate copper mixture. (3) Prepare a 0.17% (w / w) aqueous solution of polyvinyl alcohol (PVA), and then add sodium sulfate to prepare a 0.29 mol / L sodium sulfate / polyvinyl alcohol solution; (4) Add the barium copper mixture to a sodium sulfate / polyvinyl alcohol solution of the same molar concentration. The volume ratio of the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution is 1:1.9. The addition rate is 58 mL / min, the mixing and stirring rate is 800 r / min, and the mixture is stirred for 24 h after the addition is completed to obtain a suspension. (5) Place the precipitate, remove the supernatant, dry it, and then transfer the precipitate to a sintering furnace. Heat it to 884°C at a heating rate of 17°C / min, keep it at that temperature for 2 hours, and then let it cool naturally to room temperature to obtain barium sulfate / copper oxide antibacterial developer with a particle size distribution range of 8~74μm.

[0042] The preparation method of the bone cement kit is as follows: (1) Mix 64% by weight of polyacrylate (containing BPO) with 36% of antibacterial developer evenly, transfer to transparent bowl 1, and seal; (2) Mix 1.5% by weight of N,N-dimethyl-p-toluidine, 0.05% hydroquinone and 98.45% methyl methacrylate evenly, pour into ampoule 2, seal with flame drawing, install protective cap 3 on ampoule 2, and overlap the first protrusion 21 and the second protrusion 31. (3) Place the transparent bowl 1, the ampoule 2 with the protective cap 3 installed, and the guide tube 4 into the blister box and seal it; (4) When using, open the blister pack, take out the transparent bowl 1, ampoule 2 and guide tube 4; (5) Connect the guide tube 4 to the protective cap 3 of the ampoule 2 via a threaded structure; (6) Press down the protective cap 3 and the first protrusion 21 of the three rings of the ampoule 2 to overlap, and the needle 42 in the guide tube 4 punctures the ampoule 2; (7) Open the transparent bowl 1 and pour all the liquid in the ampoule 2 into the powder in the transparent bowl 1 through the guide tube 4. The filter plate 43 filters out the glass shards. (8) Use the upper pipe structure of the guide tube 4 to stir and mix the bone cement for 60 seconds. After mixing evenly, the bone cement has a 13-minute operation time and a 16-minute curing time to complete the filling and fixation.

[0043] Antibacterial bone cement was prepared into Φ12mm×2mm discs. An extract was prepared by adding 5mL of extraction medium (MEM medium containing serum) to 1g of the cement and incubating at 37±1℃ for 24±2 hours. The extract was then used to test the relative cell viability according to the extract test method specified in GB / T16886.5. Figure 13 As shown, the relative cell viability of the sample extract was 87.5%, with no potential cytotoxicity (greater than 70%), and good biocompatibility. Specific Implementation Example 6

[0044] Antibacterial bone cement kit, consisting of bone cement and a sealing protection device.

[0045] Bone cement consists of two parts: powder and liquid. The solid-liquid ratio of the bone cement powder to the liquid is 2g:1mL. The bone cement powder is composed of the following raw materials by mass percentage: 75% polyacrylate and 25% antibacterial contrast agent. The bone cement liquid is composed of the following raw materials by mass percentage: 1.8% N,N-dimethyl-p-toluidine, 0.05% hydroquinone, and 98.15% methyl methacrylate. The antibacterial contrast agent is an 81% barium sulfate / 19% copper oxide complex. The preparation method of the antibacterial developing agent is as follows: (1) Prepare barium nitrate solution and copper nitrate solution of the same concentration (0.07 mol / L); (2) Add copper nitrate solution to barium nitrate solution at a volume ratio of 81:19 and mix for 24 hours to obtain a uniform barium nitrate copper nitrate mixture. (3) Prepare a 0.17% (w / w) aqueous solution of polyvinyl alcohol (PVA), and then add sodium sulfate to prepare a 0.07 mol / L sodium sulfate / polyvinyl alcohol solution; (4) Add the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution of the same molar concentration. The volume ratio of the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution is 1:1.3. The addition rate is 39 mL / min. The mixing and stirring rate is 800 r / min. After the addition is complete, mix for 24 h to obtain a suspension. (5) Place the precipitate, remove the supernatant, dry it, and then transfer the precipitate to a sintering furnace. Heat it to 855°C at a heating rate of 9°C / min, keep it at that temperature for 2 hours, and then let it cool naturally to room temperature to obtain barium sulfate / copper oxide antibacterial developer with a particle size distribution range of 12~85μm.

[0046] The preparation method of the bone cement kit is as follows: (1) Mix 75% by weight of polyacrylate (containing BPO) with 25% of antibacterial developer evenly, transfer to transparent bowl 1, and seal; (2) Mix 1.8% by weight of N,N-dimethyl-p-toluidine, 0.05% hydroquinone and 98.15% methyl methacrylate evenly, pour into ampoule 2, seal with flame drawing, install protective cap 3 on ampoule 2, and overlap the first protrusion 21 and the second protrusion 31. (3) Place the transparent bowl 1, the ampoule 2 with the protective cap 3 installed, and the guide tube 4 into the blister box and seal it; (4) When using, open the blister pack, take out the transparent bowl 1, ampoule 2 and guide tube 4; (5) Connect the guide tube 4 to the protective cap 3 of the ampoule 2 via a threaded structure; (6) Press down the protective cap 3 and the first protrusion 21 of the three rings of the ampoule 2 to overlap, and the needle 42 in the guide tube 4 punctures the ampoule 2; (7) Open the transparent bowl 1 and pour all the liquid in the ampoule 2 into the powder in the transparent bowl 1 through the guide tube 4. The filter plate 43 filters out the glass shards. (8) Use the upper pipe structure of the guide tube 4 to stir and mix the bone cement for 60 seconds. After mixing evenly, the bone cement has an operation time of 11 minutes and a curing time of 15 minutes to complete the filling and fixation.

[0047] Antibacterial bone cement was prepared into Φ12mm×2mm discs. An extract was prepared by adding 5mL of extraction medium (MEM medium containing serum) to 1g of the cement and incubating at 37±1℃ for 24±2 hours. The extract was then used to test the relative cell viability according to the extract test method specified in GB / T16886.5. Figure 7 As shown, the relative cell viability of the sample extract was 89.1%, with no potential cytotoxicity (greater than 70%), and good biocompatibility. Specific Implementation Example 7

[0048] Antibacterial bone cement kit, consisting of bone cement and a sealing protection device.

[0049] Bone cement consists of two parts: powder and liquid. The solid-liquid ratio of the bone cement powder to the liquid is 2g:1mL. The bone cement powder is composed of the following raw materials by mass percentage: 89% polyacrylate and 11% antibacterial contrast agent. The bone cement liquid is composed of the following raw materials by mass percentage: 1.9% N,N-dimethyl-p-toluidine, 0.05% hydroquinone, and 98.05% methyl methacrylate. The antibacterial contrast agent is a 68% barium sulfate / 32% copper oxide complex. The preparation method of the antibacterial developing agent is as follows: (1) Prepare barium nitrate solution and copper nitrate solution of the same concentration (0.31 mol / L); (2) Add the copper nitrate solution to the barium nitrate solution at a volume ratio of 68:32 and mix for 24 hours to obtain a uniform barium nitrate copper mixture. (3) Prepare a 0.61% (w / w) aqueous solution of polyvinyl alcohol (PVA), and then add sodium sulfate to prepare a 0.31 mol / L sodium sulfate / polyvinyl alcohol solution; (4) Add the barium copper mixture to a sodium sulfate / polyvinyl alcohol solution of the same molar concentration. The volume ratio of the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution is 1:2.1. The addition rate is 29 mL / min. The mixing and stirring rate is 800 r / min. After the addition is complete, mix for 24 h to obtain a suspension. (5) Place the precipitate, remove the supernatant, dry it, and then transfer the precipitate to a sintering furnace. Heat it to 897°C at a heating rate of 23°C / min, keep it at that temperature for 2 hours, and then let it cool naturally to room temperature to obtain barium sulfate / copper oxide antibacterial developer with a particle size distribution range of 15~74μm.

[0050] The preparation method of the bone cement kit is as follows: (1) Mix 89% by weight of polyacrylate (containing BPO) with 11% of antibacterial developer evenly, transfer to transparent bowl 1, and seal; (2) Mix 1.9% by weight of N,N-dimethyl-p-toluidine, 0.05% hydroquinone and 98.05% methyl methacrylate evenly, pour into ampoule 2, seal with flame drawing, install protective cap 3 on ampoule 2, and overlap the first protrusion 21 and the second protrusion 31. (3) Place the transparent bowl 1, the ampoule 2 with the protective cap 3 installed, and the guide tube 4 into the blister box and seal it; (4) When using, open the blister pack, take out the transparent bowl 1, ampoule 2 and guide tube 4; (5) Connect the guide tube 4 to the protective cap 3 of the ampoule 2 via a threaded structure; (6) Press down the protective cap 3 and the first protrusion 21 of the three rings of the ampoule 2 to overlap, and the needle 42 in the guide tube 4 punctures the ampoule 2; (7) Open the transparent bowl 1 and pour all the liquid in the ampoule 2 into the powder in the transparent bowl 1 through the guide tube 4. The filter plate 43 filters out the glass shards. (8) Use the upper pipe structure of the guide tube 4 to stir and mix the bone cement for 60 seconds. After mixing evenly, the bone cement has a 10-minute operation time and a 14-minute curing time to complete the filling and fixation.

[0051] In the description of this invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. The terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance. Furthermore, unless otherwise explicitly specified and limited, the terms "installed," "connected," and "linked" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances. Moreover, the terms “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0052] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. An antibacterial bone cement, characterized in that: Bone cement consists of two parts: powder and liquid. The powder includes polyacrylate and an antibacterial contrast agent, while the liquid includes N,N-dimethyl-p-toluidine, hydroquinone, and methyl methacrylate. The antibacterial contrast agent is a barium sulfate / copper oxide complex.

2. The antibacterial bone cement according to claim 1, characterized in that, The solid-liquid ratio of the bone cement powder and liquid is (1-3) g: 1 mL; The bone cement powder is composed of the following raw materials by weight percentage: 60%~90% polyacrylate and 10%~40% antibacterial contrast agent; The liquid bone cement is composed of the following raw materials in the indicated mass percentages: N,N-dimethyl-p-toluidine 0.5%~5%, hydroquinone 0.05%~2%, and methyl methacrylate 93%~99.45%.

3. The antibacterial bone cement according to claim 1, characterized in that, The antibacterial developing agent comprises copper oxide in a mass percentage of 10% to 50%, and barium sulfate in a mass percentage of 50% to 90%.

4. The antibacterial bone cement according to claim 1, characterized in that, The method for preparing the antibacterial developing agent is as follows: (1) Prepare barium nitrate solution and copper nitrate solution of the same concentration from 0.02 mol / L to 0.34 mol / L; (2) Add the copper nitrate solution to the barium nitrate solution at a volume ratio of 50~95:5~50 and mix for 2h-24h to obtain a uniform barium nitrate copper mixture. (3) Prepare a 0.01%~0.65% (w / w) polyvinyl alcohol aqueous solution, and then add sodium sulfate to prepare a 0.02 mol / L~0.34 mol / L sodium sulfate / polyvinyl alcohol solution; (4) Add the barium copper mixture to a sodium sulfate / polyvinyl alcohol solution of the same molar concentration. The volume ratio of the barium copper mixture to the sodium sulfate / polyvinyl alcohol solution is 1:1~2.

3. The addition rate is (12.5~62.5) mL / min. The mixing and stirring rate is (200~900) r / min. After the addition is complete, mix for (12~48) h to obtain a suspension. (5) Place the precipitate, remove the supernatant, dry it, and then transfer the precipitate to a sintering furnace. Heat it to (700~900)℃ at a heating rate of (7.0~35.0)℃ / min, keep it at that temperature for (2~6h), and then cool it naturally to room temperature to obtain barium sulfate / copper oxide antibacterial developer with a particle size distribution range of (2~108)μm.

5. An antibacterial bone cement kit comprising the antibacterial bone cement as described in any one of claims 1-4, characterized in that: The product includes the bone cement and a sealing and protective device. The sealing and protective device includes a blister box, a transparent bowl, an ampoule, a protective cap, and a guide tube. The transparent bowl is the inner packaging for the powder, the ampoule is the inner packaging for the liquid, and the upper part is equipped with a protective cap. The blister box is the middle packaging. The transparent bowl, ampoule, protective cap, and guide tube are packaged together in the blister box.

6. The antibacterial bone cement kit according to claim 5, characterized in that: The blister box includes a blister film, the transparent bowl includes a blister film, the upper end of the ampoule has N+1 first protrusions, where N>1, the lower end of the protective cap has N+1 second protrusions, the protective cap is detachably mounted on the ampoule, the upper end of the protective cap has an internal thread structure for connecting the guide tube, the guide tube is a long pointed tube structure with a hollow tube in the middle and an external thread structure at the lower end for connecting the protective cap, and the guide tube has a needle filter structure inside.

7. The antibacterial bone cement kit according to claim 6, characterized in that: The needle filter structure includes a needle and a filter plate, and the filter plate is provided with filter plate holes.

8. The antibacterial bone cement kit according to claim 6, characterized in that: The transparent bowl is made of polypropylene, the blister film is made of Tyvek, and the ampoule is made of borosilicate glass. The first protrusions are spaced (5-10) mm apart, with a width of (2-4) mm and a height of (2-5) mm. The protective cap is made of polypropylene. The second protrusions are spaced (5-10) mm apart, with a width of (2-4) mm and a height of (2-5) mm. The connection between the ampoule and the protective cap is such that the lower N turns of the second protrusion on the protective cap coincide with the upper N turns of the first protrusion on the ampoule, where N > 1.

9. The antibacterial bone cement kit according to claim 8, characterized in that: The filter plate in the guide tube has a hole diameter of (0.05~0.48) mm and a thickness of (1~5) mm. The upper end of the guide tube is a cylindrical structure with an outer diameter of (6-10) mm and an inner diameter of (4-6) mm. The blister box contains one bowl groove, one guide tube groove, and one ampoule bottle groove.

10. A method for preparing a bone cement kit using the antibacterial bone cement as described in any one of claims 1-4, characterized in that: (1) Mix a measured amount of polyacrylate with the antibacterial developer evenly, transfer to a transparent bowl, and seal with plastic; (2) Mix a measured amount of N,N-dimethyl-p-toluidine, hydroquinone, and methyl methacrylate evenly, pour the mixture into an ampoule, seal it with a flame-drawn seal, install the protective cap onto the ampoule, with N convex rings overlapping and N greater than 1; (3) Place the transparent bowl, the ampoule with the protective cap, and the guide tube into the blister pack and seal it. (4) When using, open the blister pack, take out the transparent bowl, ampoule, and guide tube; (5) Connect the guide tube to the ampoule cap using a threaded connection; (6) Press down the protective cap and make it coincide with the first protrusion of the N+1 ring of the ampoule. The needle in the guide tube punctures the ampoule. (7) Open the transparent bowl and pour all the liquid in the ampoule into the powder in the transparent bowl through the guide tube. Filter out the glass shards with the filter plate. (8) Use the upper end of the guide tube to mix the bone cement for 15s~60s. After mixing evenly, the bone cement has an operation time of 5min~18min and a curing time of 15min~30min to complete the filling and fixation.

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