阅读说明：本技术 一种纳米骨粘合剂及其制备方法 (Nano bone adhesive and preparation method thereof ) 是由 王楚峰 朱剑熹 于 2021-07-07 设计创作，主要内容包括：一种纳米骨粘合剂及其制备方法,为了避免抗生素和金属银对人体带来的潜在危害,本发明创造性地掺入纳米金属锌/钴赋予骨粘合剂优异的抗菌性能。锌和钴都是人体必需的微量元素,锌在体内与80多种酶的活性有关,许多蛋白质、类固醇激素及甲状腺素的受体的DNA结合区,都有锌参与形成的锌指结构,在转录调控中起重要的作用；钴是维生素B-(12)的重要组成部分,人体缺乏维生素B-(12)时会导致巨幼细胞贫血。因此,纳米金属锌/钴可以在对人体无害的情况下提高骨粘合剂的抗菌性能。(The invention discloses a nano bone adhesive and a preparation method thereof, aiming at avoiding potential harm of antibiotics and metallic silver to human bodies, nano metallic zinc/cobalt is creatively doped to endow the bone adhesive with excellent antibacterial performance. Zinc and cobalt are all essential microelements for human body, zinc is related to the activity of more than 80 enzymes in vivo, and DNA binding regions of receptors of a plurality of proteins, steroid hormones and thyroxine have zinc fingers which are formed by zinc and play an important role in transcriptional regulation; cobalt is vitamin B 12 Is an important component of the human body, and the human body is lack of vitamin B 12 Megaloblastic anemia can result. Therefore, the nano metal zinc/cobalt can improve the antibacterial performance of the bone adhesive under the condition of no harm to human bodies.)

1. A preparation method of a nanometer bone adhesive is characterized in that Si-stabilized alpha-tricalcium phosphate nanometer powder, hydroxyapatite nanometer powder and metal nanometer powder are ground for 30-60min under the condition of 500r/min and 300-;

2.5-5 wt% of Na is prepared by taking double distilled water as solvent₂HPO₄The solution is used as a liquid phase;

mixing the liquid phase and the solid mixture into a container at a liquid-solid mass ratio of 0.5-0.7, and mixing for 100-150s to obtain the pasty bone cement.

2. A method of making according to claim 1, wherein: the dosage of the Si-stabilized alpha-tricalcium phosphate nano powder is 93.2 wt% -96.4 wt%.

3. A method of making according to claim 1, wherein: the dosage of the hydroxyapatite nano powder is 2-3 wt%.

4. A method of making according to claim 1, wherein: the metal nano powder is one or two of nano zinc and nano cobalt.

5. A method of making according to claim 1, wherein: the dosage of the metal nano powder is 1.6-4.8 wt%.

6. A method of making according to claim 1, wherein: the average grain diameter of the metal nano powder is 50 nm.

7. A method of making according to claim 1, wherein: the preparation process of the Si-stabilized alpha-tricalcium phosphate nano powder comprises the following steps: mixing CDHA with amorphous silica with SiO₂/(CDHA+SiO₂) Mixing the materials in a weight ratio of 1.88, carrying out ultrasonic treatment in double distilled water for 20min, and then putting the suspension into a planetary ball mill for treatment for 10h, wherein the ball milling rotating speed is 250 r/min; then drying at 110 ℃ for 24h, and sintering the obtained powder at 1250 ℃ for 2h, wherein the temperature rise rate during sintering is 5 ℃/min.

8. A method of making according to claim 1, wherein: the preparation process of the hydroxyapatite nano powder comprises the following steps: respectively preparing Ca (NO)₃)₂And P₂O₅To Ca (NO) in an alcohol solution of₃)₂The phosphorus-containing solution was added dropwise to the solution (final solution Ca/P ratio 1.67) and after aging at room temperature for 24h, dried at 110 c and then calcified at 700 c for 1 h.

9. A nano bone cement characterized by: the bone cement is prepared by the method of any one of claims 1-8.

Technical Field

The invention relates to the field of nano materials, in particular to a nano bone adhesive and a preparation method thereof.

Background

Bone cement is a medical material used in orthopedic surgery, and is also called bone cement because of its partial physical properties and its solidified appearance and shape rather like white cement for construction and decoration. At present, the medical bone adhesive is a novel fracture fixing material, can ensure that fracture fragments are well restored and fixed, and solves the problems of complicated operation, high cost, susceptibility to infection of affected parts and the like of a plurality of traditional treatments of comminuted fracture due to the advantages of stable performance, simple operation, easy plasticity and the like. Currently, there are mainly 4 types of bone cements commonly used for medical purposes: polymethyl methacrylate (PMMA), alpha-Cyanoacrylate (CAs), Magnesium Phosphate (MP), Calcium Phosphate (CP).

In order to reduce the risk of infection around the human bone prosthesis, a heat stable antibiotic is often injected into the bone cement to form an antibacterial bone cement. However, the potential harm that antibiotics pose to humans is difficult to gauge. Meanwhile, the researchers add metallic silver to the bone cement to improve the antibacterial performance, however, the silver is not a necessary trace element for the human body, and the side effect on the human body is not clear, for example, Hadrup N and the like (organic toxicity of silver, silver nanoparticles and colloidal silver a review) summarize reports about the toxic and side reaction of AgNPs proved by animal experiments, including death, weight reduction, activity reduction, neurotransmitter change, liver enzyme change, heart enlargement, immune injury and the like. In view of this, how to impart excellent antibacterial properties to bone cement without using antibiotics and metallic silver is a problem which is urgently needed to be solved.

Disclosure of Invention

In view of the problems of the prior art, the present invention aims to provide a nano bone cement and a preparation method thereof, wherein the antibacterial performance of the nano bone cement is improved by doping nano metal zinc/cobalt into the bone cement.

A preparation method of a nanometer bone adhesive is characterized in that Si-stabilized alpha-tricalcium phosphate nanometer powder, hydroxyapatite nanometer powder and metal nanometer powder are ground for 30-60min under the condition of 500r/min and 300-;

2.5-5 wt% of Na is prepared by taking double distilled water as solvent₂HPO₄The solution is used as a liquid phase;

mixing the liquid phase and the solid mixture into a container at a liquid-solid mass ratio of 0.5-0.7, and mixing for 100-150s to obtain the pasty bone cement.

Furthermore, the dosage of the Si-stabilized alpha-tricalcium phosphate nano powder is 93.2 wt% -96.4 wt%.

Furthermore, the dosage of the hydroxyapatite nano powder is 2-3 wt%.

Further, the metal nano powder is one or two of nano zinc and nano cobalt.

Furthermore, the dosage of the metal nano powder is 1.6 wt% -4.8 wt%.

Further, the average particle size of the metal nano powder is 50 nm.

Further, the preparation process of the Si-stabilized alpha-tricalcium phosphate nano powder comprises the following steps: mixing CDHA with amorphous silica with SiO₂/(CDHA+SiO₂) Mixing the mixture according to the weight ratio of 1.88, carrying out ultrasonic treatment in double distilled water for 20min, and then putting the suspension into a planetary ball mill for treatment for 10h, wherein the ball milling rotating speed is 250 r/min. Then drying at 110 ℃ for 24h, and sintering the obtained powder at 1250 ℃ for 2h, wherein the temperature rise rate during sintering is 5 ℃/min.

Further, the preparation process of the hydroxyapatite nano powder comprises the following steps: respectively preparing Ca (NO)₃)₂And P₂O₅To Ca (NO) in an alcohol solution of₃)₂The phosphorus-containing solution was added dropwise to the solution (final solution Ca/P ratio 1.67) and after aging at room temperature for 24h, dried at 110 c and then calcified at 700 c for 1 h.

The invention also provides a nano bone adhesive prepared by the method.

In order to avoid potential harm of antibiotics and metallic silver to human bodies, the invention creatively incorporates nano-metallic zinc/cobalt to endow the bone adhesive with excellent antibacterial performance. Zinc and cobalt are all essential microelements for human body, zinc is related to the activity of more than 80 enzymes in vivo, and DNA binding regions of receptors of a plurality of proteins, steroid hormones and thyroxine have zinc fingers which are formed by zinc and play an important role in transcriptional regulation; cobalt is vitamin B₁₂Is an important component of the human body, and the human body is lack of vitamin B₁₂Megaloblastic anemia can result. Therefore, the nano metal zinc/cobalt is doped, so that the antibacterial performance of the bone adhesive can be improved under the condition of no harm to a human body.

Detailed Description

The technical effects of the present invention are demonstrated below by specific examples, but the embodiments of the present invention are not limited thereto.

Preparing CDHA: respectively preparing Ca (NO)₃)₂·4H₂O and P₂O₅In which P is₂O₅The amount of (A) is 1mol, Ca (NO)₃)₂·4H₂The amount of O species was 3 mol. Mixing the two solutions, magnetically stirring for 24h, aging at room temperature for 24h, drying at 110 deg.C for 24h, and calcification at 600 deg.C for 1h to obtain CDHA.

Preparing Si-stabilized alpha-tricalcium phosphate nano powder: mixing the prepared CDHA with amorphous silica in SiO₂/(CDHA+SiO₂) Mixing the mixture according to the weight ratio of 1.88, carrying out ultrasonic treatment in double distilled water for 20min, and then putting the suspension into a planetary ball mill for treatment for 10h, wherein the ball milling rotating speed is 250 r/min. Then drying at 110 ℃ for 24h, and sintering the obtained powder at 1250 ℃ for 2h, wherein the temperature rise rate during sintering is 5 ℃/min.

Preparing hydroxyapatite nano powder: respectively preparing Ca (NO)₃)₂And P₂O₅To Ca (NO) in an alcohol solution of₃)₂Adding a phosphorus-containing solution dropwise into the solution (the Ca/P ratio of the final solution is 1.67), aging at room temperature for 24h, drying at 110 ℃, and then carrying out calcification treatment at 700 ℃ for 1h to obtain the hydroxyapatite nano powder.

The crystallite dimension of the Si-stable alpha-tricalcium phosphate nano powder prepared by the method is 16 +/-1.2 nm, and the crystallite dimension of the hydroxyapatite nano powder is 49 +/-2.9 nm.

Example 1

Carrying out ball milling treatment on 94.8 wt% of Si-stabilized alpha-tricalcium phosphate nano powder, 2 wt% of hydroxyapatite nano powder and 3.2 wt% of metal cobalt nano powder (the average particle size is 50nm) for 30min under the condition of 300r/min to obtain a solid mixture. 2.5 wt% Na is prepared by using double distilled water as solvent₂HPO₄The solution is used as a liquid phase. Mixing the liquid phase and the solid mixture into a syringe at a liquid-solid mass ratio of 0.5, mixing for 150 seconds to obtain a paste, injecting the paste onto the surface of the titanium alloy substrate, and sufficiently solidifying the paste in a protective atmosphere.

Example 2

Grinding 96.4 wt% of Si-stabilized alpha-tricalcium phosphate nano powder, 2 wt% of hydroxyapatite nano powder and 1.6 wt% of metal zinc nano powder (the average particle size is 50nm) for 30min under the condition of 300r/min to obtain a solid mixture. 2.5 wt% Na is prepared by using double distilled water as solvent₂HPO₄The solution is used as a liquid phase. Mixing the liquid phase and the solid mixture into a syringe at a liquid-solid mass ratio of 0.5, mixing for 150 seconds to obtain a paste, injecting the paste onto the surface of the titanium alloy substrate, and sufficiently solidifying the paste in a protective atmosphere.

Example 3

And (3) grinding 93.2 wt% of Si-stabilized alpha-tricalcium phosphate nano powder, 2 wt% of hydroxyapatite nano powder, 3.2 wt% of metal cobalt nano powder (the average particle size is 50nm) and 1.6 wt% of metal zinc nano powder (the average particle size is 50nm) for 30min under the condition of 300r/min to obtain a solid mixture. 2.5 wt% Na is prepared by using double distilled water as solvent₂HPO₄The solution is used as a liquid phase. Mixing the liquid phase and the solid mixture into a syringe at a liquid-solid mass ratio of 0.5, mixing for 150 seconds to obtain a paste, injecting the paste onto the surface of the titanium alloy substrate, and sufficiently solidifying the paste in a protective atmosphere.

Example 4

And (3) grinding 93.2 wt% of Si-stabilized alpha-tricalcium phosphate nano powder, 2 wt% of hydroxyapatite nano powder and 4.8 wt% of metal cobalt nano powder (the average particle size is 50nm) for 30min under the condition of 300r/min to obtain a solid mixture. 2.5 wt% Na is prepared by using double distilled water as solvent₂HPO₄The solution is used as a liquid phase. Mixing the liquid phase and the solid mixture into a syringe at a liquid-solid mass ratio of 0.5, mixing for 150 seconds to obtain a paste, injecting the paste onto the surface of the titanium alloy substrate, and sufficiently solidifying the paste in a protective atmosphere.

Example 5

93.2 wt% of Si-stabilized alpha-tricalcium phosphate nano powder, 2 wt% of hydroxyapatite nano powder and 4.8 wt% of metallic zinc nano powder (average grain diameter is 50)nm) and ball grinding treatment is carried out for 30min under the condition of 300r/min to obtain a solid mixture. 2.5 wt% Na is prepared by using double distilled water as solvent₂HPO₄The solution is used as a liquid phase. Mixing the liquid phase and the solid mixture into a syringe at a liquid-solid mass ratio of 0.5, mixing for 150 seconds to obtain a paste, injecting the paste onto the surface of the titanium alloy substrate, and sufficiently solidifying the paste in a protective atmosphere.

Example 6

Grinding 96.4 wt% of Si-stabilized alpha-tricalcium phosphate nano powder, 2 wt% of hydroxyapatite nano powder and 1.6 wt% of metal cobalt nano powder (the average particle size is 50nm) for 30min under the condition of 300r/min to obtain a solid mixture. 2.5 wt% Na is prepared by using double distilled water as solvent₂HPO₄The solution is used as a liquid phase. Mixing the liquid phase and the solid mixture into a syringe at a liquid-solid mass ratio of 0.5, mixing for 150 seconds to obtain a paste, injecting the paste onto the surface of the titanium alloy substrate, and sufficiently solidifying the paste in a protective atmosphere.

Example 7

Carrying out ball milling treatment on 94.8 wt% of Si-stabilized alpha-tricalcium phosphate nano powder, 2 wt% of hydroxyapatite nano powder and 3.2 wt% of metal zinc nano powder (the average particle size is 50nm) for 30min under the condition of 300r/min to obtain a solid mixture. 2.5 wt% Na is prepared by using double distilled water as solvent₂HPO₄The solution is used as a liquid phase. Mixing the liquid phase and the solid mixture into a syringe at a liquid-solid mass ratio of 0.5, mixing for 150 seconds to obtain a paste, injecting the paste onto the surface of the titanium alloy substrate, and sufficiently solidifying the paste in a protective atmosphere.

Example 8

And (3) grinding 93.2 wt% of Si-stabilized alpha-tricalcium phosphate nano powder, 2 wt% of hydroxyapatite nano powder, 3.2 wt% of metal zinc nano powder (the average particle size is 50nm) and 1.6 wt% of metal cobalt nano powder (the average particle size is 50nm) for 30min under the condition of 300r/min to obtain a solid mixture. 2.5 wt% Na is prepared by using double distilled water as solvent₂HPO₄The solution is used as a liquid phase. Mixing the liquid phase and the solid at a ratio of 0.5 by mass of the liquid to the solidThe mixture was mixed in a syringe for 150 seconds to obtain a paste, and then the paste was injected onto the surface of the titanium alloy substrate to sufficiently solidify the paste in a protective atmosphere.

Next, we tested the antibacterial performance of each of the above samples, and the specific method was: concentration of the selected bacterial liquid is 4X 10⁶The bacterial liquid for test (cfu/ml) of Staphylococcus aureus was added to the surface of the sample in an amount of 0.2ml, and the mixture was treated at 37 ℃ and RH>Culturing for 48h under 90% conditions, then taking out a sample, counting viable bacteria, and obtaining the antibacterial rate through counting. Each sample was subjected to 5 parallel tests, and bone cement without metal nanopowder was used as a control group. Wherein, the formula for calculating the antibacterial rate is as follows:

R(％)＝(A-B)/A×100

in the formula: r represents the antibacterial rate;

a represents the average number of recovered bacteria in the control group;

b represents the average number of recovered bacteria of the samples in examples.

TABLE 1 antimicrobial Rate for each of the samples of examples 1-8

Numbering	Antibacterial ratio/%)
		Example 1	75.4
Example 2	59.8
		Example 3	96.3
Example 4	86.1
		Example 5	79.3
Example 6	65.0
		Example 7	70.9
Example 8	83.5

The antibacterial property can be endowed by doping the nano metal zinc/cobalt into the bone cement, and when the dosage of the zinc and the cobalt meets the specific conditions (example 3), the antibacterial rate is as high as 96.3 percent.

The above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and variations can be made without departing from the technical principle of the present invention, and these modifications and variations should also be regarded as the protection scope of the present invention.