Preparation process of novel composite bone cement with biological activity

Abstract

The invention relates to the technical field of biomedical materials, in particular to a preparation process of novel composite bone cement with biological activity, which comprises the following steps: calcining calcium phosphate in a calcining furnace at 800-1000 DEG C for 3 hours, cooling to 20 DEG C, grinding the calcium phosphate by using a grinding machine until the diameter is less than 100 mu m, and drying to obtain the novel composite bone cement with biological activity. Calcium phosphate micro powder is obtained; by fusing the calcium phosphate, the nano-hydroxyapatite, the bioglass and the collagen, the material has a mechanical support function of an inorganic phase and biological activity of an organic phase, the nano-hydroxyapatite is extremely similar to human bone minerals and can promote osteoblast attachment and growth, and the collagen constructs a bionic microenvironment and accelerates new bone formation, so that the material can be used for treating osteoporosis. The bone repair efficiency is obviously improved.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, in particular to a preparation process of a novel composite bone cement with biological activity. Background Art

[0002] Bone glue is a biomaterial widely used in orthopedic surgery, primarily for bone defect repair, fracture fixation, artificial joint fixation, and vertebral reshaping. Although traditional polymethyl methacrylate (PMMA) bone glue has high mechanical strength, its bioinertness, lack of bone inductivity, and heat release during curing can lead to damage to surrounding tissues and pose a long-term risk of poor integration with the host skeleton. In recent years, calcium phosphate-based bone glue (CPC) has attracted widespread attention due to its excellent biocompatibility, degradability, and chemical composition similar to natural bone. However, pure calcium phosphate bone glue has problems such as brittleness, uncontrollable curing time, and lack of bioactive factors, which limit its application in load-bearing bone repair. In addition, the mechanical properties and bone integration ability of traditional bone glue still need to be improved to meet the clinical needs for rapid bone regeneration and long-term stability. Summary of the Invention

[0003] The purpose of the present invention is to provide a novel process for preparing composite bone cement with biological activity to solve the problems raised in the above background technology.

[0004] The technical solution of the present invention is: a preparation process of a novel composite bone cement with biological activity, comprising the following preparation methods: The calcium phosphate is placed in a calcining furnace and calcined at a temperature of 800-1000°C for 3 hours, then cooled to 20°C, and then ground into a particle diameter of less than 100 μm using a grinder to obtain calcium phosphate powder; The nano-hydroxyapatite was placed in a vacuum drying oven at a temperature between 60°C and 80°C, and dried for 4-6 hours. After drying, anhydrous ethanol was added at a ratio of 1:10, and ultrasonically dispersed for 45-60 minutes using an ultrasonic disperser to obtain nano-hydroxyapatite powder. Grinding the bioglass using a ball mill to a diameter of less than 5 μm to obtain bioglass powder; Then, dissolve the collagen in 0.05-0.1 mol / L acetic acid solution and stir evenly to obtain a collagen solution; Calcium phosphate micropowder, nano-hydroxyapatite micropowder, bioglass micropowder, dispersant, and initiator were added into a three-dimensional motion mixer in a ratio of 60:20:15:4:1, and stirred and mixed at a speed of 45 r / min for 45 minutes to obtain a composite bone cement powder.

[0005] Preferably, the collagen solution and the accelerator are added to a stirrer and stirred for 15 minutes to fully mix them to obtain a composite bone cement solution.

[0006] Preferably, the nano-hydroxyapatite powder and the composite bone cement liquid are mixed in a ratio of 3:1, poured into a blender and stirred for 30 seconds to fully mix, and then poured into a mold for plasticization.

[0007] Preferably, when the calcium phosphate is calcined in the calcining furnace, the heating rate is controlled to be 5-10°C / min.

[0008] Preferably, the grinder is an air flow grinder.

[0009] Preferably, the accelerator is N-dimethyl-p-toluidine, and the added amount is 0.5-1% of the mass of the collagen solution.

[0010] Preferably, the mold needs to be sterilized with high pressure steam at 121° C. for 30 minutes before use, and before pouring the mixed material, the inner surface of the mold needs to be evenly coated with a layer of medical grade release agent.

[0011] The present invention provides a novel process for preparing a bioactive composite bone cement by improving the process. Compared with the prior art, the present invention has the following improvements and advantages: First: The present invention combines calcium phosphate, nanohydroxyapatite, bioglass and collagen, so that the material has the mechanical support function of the inorganic phase and the biological activity of the organic phase. Nanohydroxyapatite is very similar to human bone mineral and can promote the attachment and growth of osteoblasts. Collagen constructs a bionic microenvironment, accelerates new bone formation, and significantly improves bone repair efficiency.

[0012] Second, the present invention adjusts the ratio of the initiator and the accelerator so that the composite bone cement can quickly solidify at room temperature while maintaining an appropriate operating time, which is convenient for clinical shaping. The three-dimensional motion mixing ensures uniform distribution of the powder. Combined with the ultrasonically treated nanoparticles, the final product has an appropriate porosity after solidification, and has both compressive strength and degradation adjustability to meet the needs of different bone defect repairs. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The present invention will be further explained below in conjunction with the accompanying drawings and examples: Figure 1 It is a flow chart of the raw material pretreatment process of the present invention; Figure 2 This is a flow chart for preparing the composite bone cement powder / liquid of the present invention; Figure 3 It is a molding and post-processing flow chart of the present invention. DETAILED DESCRIPTION

[0014] The present invention is described in detail below, clearly and completely describing the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0015] The present invention provides a novel composite bone cement preparation process with biological activity through improvement. The technical solution of the present invention is: like Figure 1 - Figure 3 As shown, a novel preparation process of a bioactive composite bone cement includes the following preparation methods: The calcium phosphate is placed in a calcining furnace and calcined at a temperature of 800-1000°C for 3 hours, then cooled to 20°C, and then ground into a particle diameter of less than 100 μm using a grinder to obtain calcium phosphate powder; The nano-hydroxyapatite was placed in a vacuum drying oven at a temperature between 60°C and 80°C, and dried for 4-6 hours. After drying, anhydrous ethanol was added at a ratio of 1:10, and ultrasonically dispersed for 45-60 minutes using an ultrasonic disperser to obtain nano-hydroxyapatite powder. Grinding the bioglass using a ball mill to a diameter of less than 5 μm to obtain bioglass powder; Then, dissolve the collagen in 0.05-0.1 mol / L acetic acid solution and stir evenly to obtain a collagen solution; Calcium phosphate micropowder, nano-hydroxyapatite micropowder, bioglass micropowder, dispersant, and initiator were added into a three-dimensional motion mixer in a ratio of 60:20:15:4:1, and stirred and mixed at a speed of 45 r / min for 45 minutes to obtain a composite bone cement powder.

[0016] Furthermore, the collagen solution and the accelerator are added to a stirrer and stirred for 15 minutes to fully mix them to obtain a composite bone cement liquid. The accelerator is fully stirred to evenly disperse the collagen solution, accelerate the subsequent curing reaction, and ensure rapid molding of the bone cement.

[0017] Furthermore, nano-hydroxyapatite powder and composite bone cement liquid are mixed in a ratio of 3:1, then poured into a blender and stirred for 30 seconds to fully mix them, and then poured into a mold for plasticization. Precise proportioning and rapid stirring ensure that the two phases are fully integrated, so that the bone cement has a uniform structure during plasticization, which is conducive to shaping into a shape that meets the requirements.

[0018] Furthermore, when calcium phosphate is calcined in a calcining furnace, the heating rate is controlled at 5-10°C / min. The stable heating rate prevents the calcium phosphate from cracking or abnormal crystal form due to sudden temperature changes, thereby ensuring its chemical structure stability and biological activity.

[0019] Furthermore, the grinder is an air flow grinder, which achieves efficient crushing through high-speed air flow collision, and can obtain calcium phosphate micropowder with smaller particle size and uniform distribution, thereby improving the strength and toughness of bone cement.

[0020] Furthermore, the accelerator is N-dimethyl-p-toluidine, and the added amount is 0.5-1% of the mass of the collagen solution. The precise amount of accelerator can not only accelerate the cross-linking and curing of collagen, but also avoid the toxicity risk caused by excessive addition, thereby ensuring the safety and effectiveness of bone cement.

[0021] Furthermore, the mold needs to be sterilized with high-pressure steam at 121°C for 30 minutes before use, and before pouring the mixed material, a layer of medical-grade release agent needs to be evenly applied to the inner surface of the mold to sterilize and eliminate bacteria and other microorganisms on the mold surface, reducing the risk of postoperative infection; the release agent facilitates the demolding of bone cement, ensures a smooth surface after molding, and reduces irritation to human tissue.

[0022] The above description is intended to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is intended to conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A process for preparing a novel composite bone cement having biological activity, characterized in that: The invention comprises the following preparation methods: The calcium phosphate is placed in a calcining furnace and calcined at a temperature of 800-1000°C for 3 hours, then cooled to 20°C, and then ground into a particle diameter of less than 100 μm using a grinder to obtain calcium phosphate powder; The nano-hydroxyapatite was placed in a vacuum drying oven at a temperature between 60°C and 80°C, and dried for 4-6 hours. After drying, anhydrous ethanol was added at a ratio of 1:10, and ultrasonically dispersed for 45-60 minutes using an ultrasonic disperser to obtain nano-hydroxyapatite powder. Grinding the bioglass using a ball mill to a diameter of less than 5 μm to obtain bioglass powder; Then, dissolve the collagen in 0.05-0.1 mol / L acetic acid solution and stir evenly to obtain a collagen solution; Calcium phosphate micropowder, nano-hydroxyapatite micropowder, bioglass micropowder, dispersant, and initiator were added into a three-dimensional motion mixer in a ratio of 60:20:15:4:1, and stirred and mixed at a speed of 45 r / min for 45 minutes to obtain a composite bone cement powder.

2. The process for preparing a novel composite bone cement with biological activity according to claim 1, characterized in that: The collagen solution and the accelerator were added into a stirrer and stirred for 15 minutes to fully mix them, thereby obtaining a composite bone cement solution.

3. The process for preparing a novel composite bone cement with biological activity according to claim 1, characterized in that: Nano-hydroxyapatite powder and composite bone cement liquid were mixed in a ratio of 3:1, poured into a blender and stirred for 30 seconds to fully mix, and then poured into a mold for plasticization.

4. The process for preparing a novel composite bone cement with biological activity according to claim 1, characterized in that: When the calcium phosphate is calcined in the calcining furnace, the heating rate is controlled to be 5-10°C / min.

5. The process for preparing a novel composite bone cement with biological activity according to claim 1, characterized in that: The grinder is an air flow grinder.

6. The process for preparing a novel composite bone cement with biological activity according to claim 2, characterized in that: The accelerator is N-dimethyl-p-toluidine, and the added amount is 0.5-1% of the mass of the collagen solution.

7. The process for preparing a novel composite bone cement with biological activity according to claim 3, characterized in that: The mold needs to be sterilized with high-pressure steam at 121°C for 30 minutes before use, and before pouring the mixed material, the inner surface of the mold needs to be evenly coated with a layer of medical-grade release agent.

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