High-activity tricalcium phosphate and preparation process thereof

Abstract

The invention belongs to the technical field of chemical engineering, and provides a high-activity tricalcium phosphate and a preparation process thereof, and the preparation process comprises the following steps: centrifuging solutions with the same density at different rotating speeds, and determining the initial rotating speed and time interval of large particle sedimentation according to a centrifugal degree change curve; and carrying out ultrasonic pretreatment on the large-particle sediment, washing with water and absolute ethyl alcohol for multiple times, drying and analyzing the components of the sediment. And then carrying out speed reduction centrifugation on the semi-settled solution after the large particles are settled, measuring parameters of the small particles, and drawing a curve to determine the optimal rotating speed and ending time of the small particle settlement. Finally, washing and drying the small-particle sediments, measuring components, calculating a mass ratio according to a calcium-phosphorus ratio of the beta-TCP precursor, and mixing the large-particle sediments and the small-particle sediments so as to precisely regulate and control sedimentation and mixing; the scheme has remarkable advantages, sedimentation parameters can be accurately determined, sedimentation and mixing of particles can be effectively regulated and controlled, it is ensured that the product meets the calcium-phosphorus ratio expectation of the beta-TCP precursor, the experiment accuracy is high, and the reliability is high.

Description

Technical Field

[0002] The invention belongs to the technical field of compound preparation, in particular to a high-activity tricalcium phosphate and a preparation process thereof. Background Art

[0004] In the traditional preparation process of highly active tricalcium phosphate precursors, due to insufficient control of the particle sedimentation link, it is difficult to accurately determine the sedimentation rate and time of large and small particles, resulting in an unstable calcium-phosphorus ratio, which not only affects the crystallinity and microstructure of the material, but also weakens the bonding effect between the implant material and human tissue in the biomedical field, affecting biocompatibility and bone conductivity. In addition, the traditional method lacks standardized procedures when dealing with sediments, resulting in rough cleaning, drying and component analysis processes, incomplete removal of impurities, and inaccurate determination of chemical composition. When mixing large and small particles, people often rely on experience rather than precise calculation and regulation, which cannot meet the strict requirements of modern high-performance materials for precise chemical stoichiometric ratios. These problems limit the application potential of highly active tricalcium phosphate precursors in hard tissue repair and tissue engineering. It is urgent to optimize the sedimentation process through technological innovation and improve the quality and performance of materials to meet the needs of modern industry and biomedicine for high-performance materials.

[0005] To this end, the present invention provides a high-activity tricalcium phosphate and a preparation process thereof. Summary of the invention

[0007] In order to make up for the deficiencies of the prior art, at least one technical problem raised in the background technology is solved.

[0008] The technical solution adopted by the present invention to solve the technical problem is: a highly active tricalcium phosphate and a preparation process thereof, comprising:

[0009] Step 1: In the same test cycle, centrifuge the same density solution at different speeds; obtain the centrifugation degree M of the same density solution at different speeds at each time point; draw a centrifugation degree change curve based on the change process of the centrifugation degree M over time ti; find the speed corresponding to the curve with the largest slope in the curve, and set it as the initial speed R0 for large particle sedimentation; fit the curve with the logistic function and determine the parameters, calculate the second-order derivative to obtain the curve gentle turning point tturn; set the large particle sedimentation centrifugation time interval to [t0, tturn];

[0010] Step 2: Place the large particle sediment into a dialysis bag; use ultrasound to pre-treat the sediment, place the dialysis bag in flowing deionized water and rinse it three times; after rinsing with water, inject anhydrous ethanol and rinse it repeatedly three times; perform chemical analysis on the dried large particle sediment, and record the calcium content Mca and phosphorus content Mp of the large particle sediment obtained by sedimentation of solutions with different densities;

[0011] Step 3: Centrifuge the semi-sedimentation solution of the same density at a gradually decreasing speed according to the initial speed R0; measure the small particle parameters and calculate the theoretical sedimentation rate and the theoretical end time point using the Stokes formula; record the centrifugal degree of the small particles at different speeds at each time point and draw its change curve; analyze the curve to obtain the first and second optimal speeds, and refine and determine the optimal speed for small particle sedimentation; judge before and after the theoretical end time point tend to obtain the end time of small particle sedimentation;

[0012] Step 4: Wash the small particle sediment three times with water and three times with anhydrous ethanol, and then dry it; determine the calcium content Mca2 and phosphorus content Mp2 of the small particle sediment obtained from the same density solution; determine the calcium-phosphorus ratio of the required β-TCP precursor; calculate the mass ratio of the large particle sediment to the small particle sediment according to the calcium-phosphorus ratio, and mix them according to the mass obtained in proportion;

[0013] As a further technical solution of the present invention, the process of obtaining the centrifugal degree M of the same density solution at different speeds at various time points is as follows:

[0014] Record the amount of precipitate and the turbidity of the supernatant produced by the same density solution at different rotation speeds at the same time point ti; perform ratio processing on the amount of precipitate and the turbidity of the supernatant corresponding to each time point; obtain the centrifugation degree M of the solution corresponding to each rotation speed for the same density solution at different rotation speeds and each time point.

[0015] As a further technical solution of the present invention, the process of fitting the curve with the logistic function and determining the parameters, and obtaining the second-order derivative to obtain the gentle turning point tturn of the curve is:

[0016] The centrifugal degree change curve is analyzed using the logistic Stefan function to fit; where a, b, c are the parameters to be fitted; using the nonlinear least squares method, the parameters a, b, c of the logistic function are fitted according to the recorded time point ti and the centrifugal degree M of the same density solution at different speeds corresponding to the time point; the second-order derivative of the logistic function The turning point tturn where the centrifugal degree change curve R begins to flatten is obtained; wherein the turning point tturn indicates that the time period before the turning point is the effective time period for the sedimentation of large particles; that is, the centrifugal time interval of the large particle sedimentation stage is [t0, tturn].

[0017] As a further technical solution of the present invention, the process of calculating the theoretical sedimentation rate and the theoretical end time point by using the Stokes formula is:

[0018] By formula The sedimentation rate of the semi-sedimented solution with the same density when the small particles are sedimented is calculated; where r is the radius of the small particle, Pk is the density of the small particle, Pf is the density of the solution, and g is the gravitational acceleration. is the dynamic viscosity of the solution;

[0019] According to the sedimentation rate of the semi-sedimented solution at the same density Estimate the theoretical end time point tend corresponding to the completion of sedimentation of small particles in the semi-sedimentation solution at this density.

[0020] As a further technical solution of the present invention, the process of analyzing the curve to obtain the first optimal speed is:

[0021] For a semi-sedimented solution of the same density, obtain a particle centrifugation degree change curve corresponding to small particle centrifugation of the semi-sedimented solution at different speeds within a time window [tturn, tend]; obtain the area of ​​each particle centrifugation degree change curve on the x-axis; compare the obtained small particle centrifugation degree change curve areas on the x-axis; find out the particle centrifugation degree change curve corresponding to the particle centrifugation degree change curve with the largest area on the x-axis; set the speed corresponding to the particle centrifugation degree change curve as the first speed Ropt1 when performing small particle sedimentation on the semi-sedimented solution.

[0022] As a further technical solution of the present invention, the method for obtaining the second optimal speed by analyzing the curve is:

[0023] Obtain the slope k1 of the particle centrifugal degree change curve at the starting time point tturn on the coordinate system, the slope k2 of the particle centrifugal degree change curve at the theoretical end time point tend on the coordinate system, and the slope k3 of the particle centrifugal degree change curve at the highest point in the coordinate system; by Get the average slope of the particle centrifugal degree change curve in the time window [tturn, tend] ; Through the formula Get the standard deviation of the slope of the centrifugal degree change curve of each particle on the coordinate system ;in is the average slope, n is the number of data points recorded in the time window; the particle centrifugal degree change curve with the largest standard deviation is obtained by comparison; the rotation speed corresponding to the particle centrifugal degree change curve is set as the second rotation speed Ropt2.

[0024] As a further technical solution of the present invention, the process of refining and determining the optimal rotation speed for small particle settling is as follows:

[0025] The speed gradient ΔR2 is further refined within the speed range of the first speed Ropt1 and the second speed Rtop2; wherein ΔR2<<ΔR1, and within this range, the particle centrifugation degree change curve whose slope on the coordinate system is the largest is found; the speed corresponding to the particle centrifugation degree change curve is set as the optimal speed for small particle sedimentation.

[0026] As a further technical solution of the present invention, the process of determining the theoretical end time point tend to obtain the end time of small particle sedimentation is as follows:

[0027] Set the particle centrifugation threshold a of the semi-sedimented solution with the same density at the end of sedimentation;

[0028] If the particle centrifugal degree Mi is less than the particle centrifugal degree threshold a at the theoretical end time point tend, then the theoretical end time point tend is taken as the end time point of small particle sedimentation completion;

[0029] If the particle centrifugation degree Mi is greater than the particle centrifugation degree threshold a at the theoretical end time point tend, the slope change rate of the centrifugation degree change curve corresponding to the optimal rotation speed for small particle sedimentation is analyzed; the starting time when the slope change rate of the curve remains in the minimum value range is selected as the end time of small particle sedimentation.

[0030] As a further technical solution of the present invention, the process of analyzing the slope change rate of the centrifugal degree change curve corresponding to the optimal rotation speed for the small particle sedimentation is as follows:

[0031] Then observe the slope of the centrifugal degree change curve corresponding to the optimal speed for small particle sedimentation at a small time interval Δt1 after the time point tend, and calculate the rate of change of the curve slope: rate of change = Where kt is the slope of the curve at time t;

[0032] If the rate of change of the slope of the centrifugal degree curve gradually approaches zero in multiple consecutive time intervals; and the rate of change of the slope of the curve continues to remain in a minimum range for a long time, it indicates that the sedimentation of small particles is basically completed.

[0033] As a further technical solution of the present invention, the mass ratio of large particle sediment to small particle sediment is calculated according to the calcium-phosphorus ratio, and the process of mixing the mass according to the ratio is as follows:

[0034] By formula The ratio of the required mass of large particle sedimentation to the required mass of small particle sedimentation is calculated; according to the ratio, the mass Mlarge of large particle sedimentation and the mass Msmall of small particle sedimentation are found within a reasonable range for mixing.

[0035] The beneficial effects of the present invention are as follows: first, the same density solution is centrifuged at different speeds, and the initial speed R0 and time interval of large particle sedimentation are determined according to the change of centrifugal degree. The calcium and phosphorus content of the large particle sediment is measured after ultrasonic, water washing and alcohol washing. Then, the same density semi-sedimentation solution is centrifuged at R0 speed reduction to determine the optimal speed and end time of small particle sedimentation. The small particle sediment is treated in the same way and then the calcium and phosphorus content is measured. Finally, the mass ratio of large and small particle sediments is determined according to the calcium-phosphorus ratio and mixed in proportion, which greatly guarantees the uniformity and stability of the β-TCP precursor components. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The present invention will be further described below in conjunction with the accompanying drawings.

[0038] Figure 1 is a flow chart of the steps of a process for preparing high-activity tricalcium phosphate according to Example 1 of the present invention;

[0039] Figure 2 This is a flow chart of the steps of a process for preparing high-activity tricalcium phosphate described in Example 2 of the present invention. DETAILED DESCRIPTION

[0041] In order to make the technical means, creative features, objectives and effects achieved by the present invention easy to understand, the present invention is further explained below in conjunction with specific implementation methods.

[0042] Example 1

[0043] A high-activity tricalcium phosphate preparation process according to an embodiment of the present invention comprises:

[0044] Ss1: adding a calcium source or a phosphorus source to a mixed solution formed by a surfactant, an organic solvent and water, respectively, and stirring to obtain a calcium source mixed solution and a phosphorus source mixed solution, respectively. The surfactant includes any one of hexadecyltrimethylammonium bromide, polyethylene glycol 600, sodium dodecyl sulfate, sodium lauryl sulfate, and dodecyl dimethyl betaine. The amount of the surfactant added is 1%-40%, and the amount of the organic solvent added is 20%-50%; the organic solvent is selected from any one of tripropylene glycol, 1,2,3-hexanetriol, and 2-methyl-1,3-propanediol.

[0045] Ss2 adds the phosphorus source mixed solution to the calcium source mixed solution dropwise in an ultrasonic environment, stirring while adding, and uses ammonia water to adjust the pH value of the solution;

[0046] After the Ss3 addition reaction is completed, continue stirring to make the solution fully mixed and allow it to stand for stratification;

[0047] Ss4 separates, washes, dries and roasts the solid to obtain the target product, β-tricalcium phosphate powder;

[0048] Example 2

[0049] like Figure 1 As shown, the present invention further optimizes the separation step in ss4;

[0050] A high-activity tricalcium phosphate preparation process according to an embodiment of the present invention comprises:

[0051] Step 1: In the same test cycle, centrifuge the same density solution at different speeds; obtain the centrifugation degree M of the same density solution at different speeds at each time point; draw a centrifugation degree change curve based on the change process of the centrifugation degree M over time ti; find the speed corresponding to the curve with the largest slope in the curve, and set it as the initial speed R0 for large particle sedimentation; fit the curve with the logistic function and determine the parameters, calculate the second-order derivative to obtain the curve gentle turning point tturn; set the large particle sedimentation centrifugation time interval to [t0, tturn];

[0052] Pour the stationary solutions of different densities into centrifuge tubes respectively; in the same test cycle and under the same conditions, centrifuge at different speeds for the solutions of the same density; record the amount of precipitate and the turbidity of the supernatant produced by the solution of the same density at different speeds at the same time points ti (i=1, 2, 3, ....n); perform ratio processing on the amount of precipitate and the turbidity of the supernatant at each time point; obtain the centrifugation degree M of the solution corresponding to each speed at different speeds and time points for the solution of the same density;

[0053] A two-dimensional rectangular coordinate system is constructed with the time point ti as the X-axis and the centrifugal degree M as the Y-axis; for the same density solution, the centrifugal degree M of the solution at each speed at different time points is marked and connected in the two-dimensional rectangular coordinate system; the centrifugal degree change curve Mt of the same density solution at different speeds is obtained;

[0054] It should be noted that there are multiple centrifugation degree change curves, each corresponding to a specific gradient speed; and for solutions of different densities, respective two-dimensional rectangular coordinate systems need to be constructed;

[0055] Analyze the centrifugal degree curve corresponding to the solution of the same density under different speed conditions;

[0056] For each speed Xi (i=1,2,3,....n), an independent linear regression model is established , where M represents the centrifugal degree of the solution corresponding to each speed Xi at different speeds and time points ti for the same density solution; β 0j is the intercept, which indicates the initial centrifugal degree of the solution at time ti=0 at different speeds Xi; β 1j is the slope, which indicates the average change in the degree of centrifugation M with each unit increase in time point ti at the speed Xi; eij is the random error term, which indicates the deviation between the actual measured value and the value predicted by the linear regression model; and the intercept β 0j and the slope β 1j are the regression coefficients of the linear regression model;

[0057] All the measurement time points n contained in each speed Xi and the corresponding solution centrifugation degree M at this time point are set as the data group corresponding to each speed Xi; for the data group corresponding to each speed Xi, the regression coefficient β in the linear regression model is estimated by the least squares method. 0j and β 1j The value of

[0058] Calculated by the formula ; ; The regression coefficient β 0j and β 1j and the starting time point t0, are substituted into the linear regression model corresponding to each speed Xi and recalculated; the M value obtained by calculation is the slope K0 of the centrifugal degree change curve corresponding to different speeds under the same density solution at the starting time point t0;

[0059] Compare the slopes K0 of the centrifugal degree change curves corresponding to different speeds at the same density at the initial stage; find the centrifugal degree change curve with the largest slope; and set the speed corresponding to the centrifugal degree change curve as the initial speed R0 of the large particle sedimentation stage;

[0060] The centrifugal degree change curve is analyzed using the logistic Stefan function Perform fitting; where a, b, c are the parameters to be fitted;

[0061] For the recorded time point ti and the centrifugal degree M of the same density solution at different speeds corresponding to the time point, by minimizing the objective function Fit the parameters a, b, c of the logistic function; by continuously adjusting the values ​​of a, b, c, S is minimized, thereby obtaining the fitting parameters a, b, c;

[0062] The second derivative of the logistic function Solve to get the turning point where the centrifugal degree curve R begins to flatten out ; Among them, the turning point tturn It means that the time period before the turning point is the effective time period for the sedimentation of large particles; that is, the centrifugal time interval of the large particle sedimentation stage is [t0,t turn ];

[0063] The semi-sedimented solutions and large particle sediments are obtained by subjecting the static solutions with different densities to large particle sedimentation.

[0064] Step 2: Place the large particle sediment into a dialysis bag; use ultrasound to pre-treat the sediment, place the dialysis bag in flowing deionized water and rinse it three times; after rinsing with water, inject anhydrous ethanol and rinse it repeatedly three times; perform chemical analysis on the dried large particle sediment, and record the calcium content Mca and phosphorus content Mp of the large particle sediment obtained by sedimentation of solutions with different densities;

[0065] Put the large particle sediment into the dialysis bag; at the beginning of the first water washing, introduce ultrasonic treatment to wash the large particle sediment for pretreatment; wherein the ultrasonic frequency, time and power are determined according to the properties of the large particles and the type of impurities, such as setting the ultrasonic frequency to 30-40kHz, the time to 5-10 minutes, and the power to 200-300W for specific large particles; then put the dialysis bag into the ultrasonic cleaner for ultrasonication;

[0066] After the ultrasonic treatment, the formal water washing operation begins; the dialysis bag is placed in a large amount of flowing deionized water to allow the deionized water to fully flush the large particle sediment in the dialysis bag; after continuous flushing for a period of time, replace it with new deionized water for another flush; the large particles in the dialysis bag are repeatedly washed three times; the large particle sediment after the washing is measured,

[0067] After three water washing processes, the dialysis bag is rinsed with anhydrous ethanol; anhydrous ethanol is slowly injected into the dialysis bag to allow large particle sediment to fully contact with anhydrous ethanol, and impurities in the large particle sediment are removed by gently shaking the dialysis bag; the ethanol containing impurities is discharged from the dialysis bag; new anhydrous ethanol is injected into the dialysis bag, and the anhydrous ethanol washing is repeated three times; after the washing is completed, the large particle sediment is left on the filter paper, and placed in a fume hood to dry naturally or dried using an infrared lamp or a hot air drying oven to remove the residual anhydrous ethanol;

[0068] Conduct chemical analysis on the dried large-particle sediment; determine and record the calcium content Mca1 and phosphorus content Mp1 of each small-particle sediment;

[0069] Step 3: Centrifuge the semi-sedimentation solution of the same density at a gradually decreasing speed according to the initial speed R0; measure the small particle parameters and calculate the theoretical sedimentation rate and the theoretical end time point using the Stokes formula; record the centrifugal degree of the small particles at different speeds at each time point and draw its change curve; analyze the curve to obtain the first and second optimal speeds, and refine and determine the optimal speed for small particle sedimentation; judge before and after the theoretical end time point tend to obtain the end time of small particle sedimentation;

[0070] The initial speed R0 in the large particle sedimentation is gradually reduced by a preset speed difference ΔR1; after each speed reduction, the semi-sedimented solution of the same density is centrifuged at the reduced speed; wherein ΔR1 is a speed difference value predetermined according to the experimental equipment and the solution properties;

[0071] The radius r and density Pk of the small particles are measured by X-ray diffraction; the dynamic viscosity of the solution is measured by capillary viscometer. ;

[0072] By formula The sedimentation rate of the semi-sedimented solution with the same density when the small particles are sedimented is calculated; where r is the radius of the small particle, Pk is the density of the small particle, Pf is the density of the solution, and g is the gravitational acceleration. is the dynamic viscosity of the solution; according to the sedimentation rate of the semi-sedimented solution at the same density Estimate the theoretical end time point tend corresponding to the completion of sedimentation of small particles in the semi-sedimentation solution at this density;

[0073] Record the amount of precipitate generated by the semi-precipitated solution of the same density at different speeds and the turbidity of the supernatant at the same time points; perform ratio processing on the amount of solution precipitate generated by the semi-precipitated solution of the same density at different speeds at each time point and the turbidity of the supernatant to obtain the centrifugal degree Mi of the small particles of the solution at each speed at each time point for the semi-precipitated solution of the same density; draw the particle centrifugal degree change curve Mit;

[0074] For the semi-sediment solution of the same density, in the time window [t turn , tend]; obtain the area of ​​each particle centrifugal degree change curve on the x-axis; compare the obtained small particle centrifugal degree change curve on the x-axis; find the particle centrifugal degree change curve corresponding to the particle centrifugal degree change curve with the largest area on the x-axis; set the speed corresponding to the particle centrifugal degree change curve as the first speed Ropt1 when the semi-sedimentation solution is subjected to small particle sedimentation;

[0075] Get the starting time point t turn The slope k1 of the particle centrifugal degree change curve in the coordinate system and the theoretical end time point t end The slope k2 of the particle centrifugal degree change curve on the coordinate system and the slope k3 of the particle centrifugal degree change curve at the highest point in the coordinate system; Get the average slope of the particle centrifugal degree change curve in the time window [tturn, tend] ; Through the formula Get the standard deviation of the slope of the centrifugal degree change curve of each particle on the coordinate system ;in is the average slope, n is the number of data points recorded in the time window; a particle centrifugal degree change curve with the largest standard deviation is obtained by comparison; and the speed corresponding to the particle centrifugal degree change curve is set as the second speed Ropt2;

[0076] Further refine the speed gradient ΔR2 within the speed interval of the first speed Ropt1 and the second speed Rtop2; wherein ΔR2<<ΔR1, and find the particle centrifugal degree change curve with the largest slope on the coordinate system within this interval; the speed corresponding to the particle centrifugal degree change curve is set as the optimal speed for small particle sedimentation;

[0077] When the semi-sedimentation solution of the same density is subjected to small particle sedimentation at the optimal speed, the trend of the particle centrifugal degree change curve Mit on the coordinate system before and after the theoretical end time point tend corresponding to the completion of sedimentation is analyzed;

[0078] Set the particle centrifugation threshold a of the semi-sedimented solution with the same density at the end of sedimentation;

[0079] If the particle centrifugal degree Mi is less than the particle centrifugal degree threshold a at the theoretical end time point tend, then the theoretical end time point tend is taken as the end time point of small particle sedimentation completion;

[0080] If the particle centrifugal degree Mi at the theoretical end time point tend> the particle centrifugal degree threshold a; then observe the slope of the centrifugal degree change curve corresponding to the optimal speed for small particle sedimentation at a small time interval Δt1 after the time point tend, and calculate the rate of change of the curve slope: rate of change = Where kt is the slope of the curve at time t;

[0081] If the slope change rate of the centrifugal degree change curve gradually approaches zero in a plurality of consecutive time intervals; and the slope change rate of the curve always remains within a minimum value range for a long time, it indicates that the small particle sedimentation is basically completed; then the starting time when the slope change rate of the curve remains within the minimum value range is selected as the end time of the small particle sedimentation;

[0082] The semi-sedimented solution obtained after the large particles of the solutions with different densities are subjected to small particle sedimentation again to obtain small particle sediment;

[0083] Step 4: Wash the small particle sediment three times with water and three times with anhydrous ethanol, and then dry it; determine the calcium content Mca2 and phosphorus content Mp2 of the small particle sediment obtained from the same density solution; determine the calcium-phosphorus ratio of the required β-TCP precursor; calculate the mass ratio of the large particle sediment to the small particle sediment according to the calcium-phosphorus ratio, and mix them according to the mass obtained in proportion;

[0084] Put the small particle sediment into a Buchner funnel, immerse the small particle sediment with deionized water and stir gently with a glass rod; then turn on the switch of the funnel to let water and impurities flow into the beaker so that the small particle sediment is intercepted by the filter paper; the deionized water washing process needs to be repeated 2 to 3 times; after the small particle sediment is washed with water, wash it again three times with anhydrous ethanol; after each washing, turn on the funnel switch to let the ethanol flow out and retain the small particle sediment; after washing, leave the small particle sediment on the filter paper and place it in a fume hood to dry naturally or use an infrared lamp or a hot air drying oven to dry it to remove the residual anhydrous ethanol;

[0085] Conduct chemical analysis on the dried small particle sediment; determine and record the calcium content Mca2 and phosphorus content Mp2 of each small particle sediment;

[0086] Determine the required calcium-phosphorus ratio X of the β-TCP precursor; by the formula The ratio of the required mass of large particle sedimentation to the required mass of small particle sedimentation is calculated; according to the ratio, the mass Mlarge of large particle sedimentation and the mass Msmall of small particle sedimentation are found within a reasonable range for mixing;

[0087] The technical scheme of the embodiment of the present invention is: first centrifuge the same density solution at different speeds, and determine the initial speed R0 and time interval of large particle sedimentation according to the change of centrifugal degree. The large particle sediment is measured for calcium and phosphorus content after ultrasound, water washing and alcohol washing. Then the same density semi-sedimentation solution is centrifuged at R0 speed reduction to determine the optimal speed and end time of small particle sedimentation. The small particle sediment is also processed and the calcium and phosphorus content is measured. Finally, the mass ratio of large and small particle sediments is determined according to the calcium-phosphorus ratio and mixed in proportion, which greatly guarantees the uniformity and stability of the β-TCP precursor component.

[0088] Example 3

[0089] The high-activity tricalcium phosphate described in the present invention is prepared by the high-activity tricalcium phosphate preparation process described in Examples 1 and 2 above.

[0090] The above shows and describes the basic principles, main features and advantages of the present invention. It should be understood by those skilled in the art that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A process for preparing highly active tricalcium phosphate, characterized in that: include: Step 1: Within the same test cycle, centrifuge the same density solution at different speeds; Obtain the centrifugal degree M of the same density solution at different speeds at each time point; According to the change process of centrifugal degree M over time ti, a centrifugal degree change curve is drawn; the speed corresponding to the curve with the largest slope in the curve is found, and it is set as the initial speed R0 for large particle sedimentation; the logistic function is used to fit the curve and determine the parameters, and the second-order derivative is calculated to obtain the gentle turning point tturn of the curve; the centrifugal time interval for large particle sedimentation is set as [t0, tturn]; Step 2: Place the large particle sediment into a dialysis bag; use ultrasound to pre-treat the sediment, place the dialysis bag in flowing deionized water and rinse it three times; after rinsing with water, inject anhydrous ethanol and rinse it repeatedly three times; perform chemical analysis on the dried large particle sediment, and record the calcium content Mca and phosphorus content Mp of the large particle sediment obtained by sedimentation of solutions with different densities; Step 3: Centrifuge the semi-sedimentation solution of the same density at a gradually decreasing speed according to the initial speed R0; measure the small particle parameters and calculate the theoretical sedimentation rate and the theoretical end time point using the Stokes formula; record the centrifugal degree of the small particles at different speeds at each time point and draw its change curve; Analyze the curve to obtain the first and second optimal speeds, and refine the optimal speed for small particle sedimentation; judge before and after the theoretical end time point tend to obtain the end time of small particle sedimentation; Step 4: Wash the small particle sediment three times with water, three times with anhydrous ethanol, and then dry; Determine the calcium content Mca2 and phosphorus content Mp2 of the small particle precipitate obtained from the same density solution; determine the required calcium-phosphorus ratio of the β-TCP precursor; calculate the mass ratio of the large particle precipitate to the small particle precipitate based on the calcium-phosphorus ratio, and mix them according to the mass obtained in proportion.

2. A process for preparing highly active tricalcium phosphate according to claim 1, characterized in that: The process of obtaining the centrifugation degree M of the same density solution at different speeds at each time point is as follows: Record the amount of precipitate and the turbidity of the supernatant produced by the same density solution at different speeds at the same time point ti; perform ratio processing on the amount of precipitate and the turbidity of the supernatant corresponding to each time point; The centrifugation degree M of the solution corresponding to each rotation speed is obtained for the same density solution at different rotation speeds and at various time points.

3. A high-activity tricalcium phosphate preparation process according to claim 1, characterized in that: The process of fitting the curve with the logistic function and determining the parameters, and obtaining the second-order derivative to obtain the gentle turning point tturn of the curve is: The centrifugal degree change curve is analyzed using the logistic Stefan function to fit; where a, b, c are the parameters to be fitted; using the nonlinear least squares method, the parameters a, b, c of the logistic function are fitted according to the recorded time point ti and the centrifugal degree M of the same density solution at different speeds corresponding to the time point; the second-order derivative of the logistic function Solve to get the turning point t where the centrifugal degree change curve R begins to flatten out turn ; Among them, the turning point t turn It means that the time period before the turning point is the effective time period for the sedimentation of large particles; that is, the centrifugal time interval of the large particle sedimentation stage is [t0,t turn ].

4. A process for preparing highly active tricalcium phosphate according to claim 1, characterized in that: The process of calculating the theoretical sedimentation rate and the theoretical end time point using the Stokes formula is: By formula The sedimentation rate of the semi-sedimented solution with the same density when the small particles are sedimented is calculated; where r is the radius of the small particle, Pk is the density of the small particle, Pf is the density of the solution, and g is the gravitational acceleration. is the dynamic viscosity of the solution; According to the sedimentation rate of the semi-sedimented solution at the same density Estimate the theoretical end time point tend corresponding to the completion of sedimentation of small particles in the semi-sedimentation solution at this density.

5. A process for preparing highly active tricalcium phosphate according to claim 1, characterized in that: The process of analyzing the curve to obtain the first optimal speed is: For the semi-sedimented solution of the same density, in the time window [t turn , tend]; obtain the area of ​​each particle centrifugation degree change curve on the x-axis; compare the areas of the obtained small particle centrifugation degree change curves on the x-axis; find the particle centrifugation degree change curve corresponding to the particle centrifugation degree change curve with the largest area on the x-axis; set the speed corresponding to the particle centrifugation degree change curve as the first speed Ropt1 when the semi-sedimentation solution is subjected to small particle sedimentation.

6. A process for preparing highly active tricalcium phosphate according to claim 5, characterized in that: The method for obtaining the second optimal speed by analyzing the curve is as follows: Get the starting time point t turn The slope k1 of the particle centrifugal degree change curve in the coordinate system and the theoretical end time point t end The slope k2 of the particle centrifugal degree change curve on the coordinate system and the slope k3 of the particle centrifugal degree change curve at the highest point in the coordinate system; Get the average slope of the particle centrifugal degree change curve in the time window [tturn, tend] ; Through the formula Get the standard deviation of the slope of the centrifugal degree change curve of each particle on the coordinate system ;in is the average slope, n is the number of data points recorded in the time window; the particle centrifugal degree change curve with the largest standard deviation is obtained by comparison; the rotation speed corresponding to the particle centrifugal degree change curve is set as the second rotation speed Ropt2.

7. A process for preparing highly active tricalcium phosphate according to claim 1, characterized in that: The process of refining and determining the optimal rotation speed for small particle settling is as follows: The speed gradient ΔR2 is further refined within the speed range of the first speed Ropt1 and the second speed Rtop2; wherein ΔR2<<ΔR1, and within this range, the particle centrifugation degree change curve whose slope on the coordinate system is the largest is found; the speed corresponding to the particle centrifugation degree change curve is set as the optimal speed for small particle sedimentation.

8. A process for preparing highly active tricalcium phosphate according to claim 1, characterized in that: The process of determining the theoretical end time point tend to obtain the end time of small particle settling is as follows: Set the particle centrifugation threshold a of the semi-sedimented solution with the same density at the end of sedimentation; If the particle centrifugal degree Mi is less than the particle centrifugal degree threshold a at the theoretical end time point tend, then the theoretical end time point tend is taken as the end time point of small particle sedimentation completion; If the particle centrifugal degree Mi at the theoretical end time point tend> the particle centrifugal degree threshold a; then observe the slope of the centrifugal degree change curve corresponding to the optimal speed for small particle sedimentation at a small time interval Δt1 after the time point tend, and calculate the rate of change of the curve slope: rate of change = Where kt is the slope of the curve at time t; If the slope change rate of the centrifugal degree change curve gradually approaches zero in multiple consecutive time intervals; and the slope change rate of the curve continues to remain in a minimum range for a long time, it indicates that the small particle sedimentation is basically completed; the starting time when the slope change rate of the curve remains in the minimum range is selected as the end time of small particle sedimentation.

9. A process for preparing highly active tricalcium phosphate according to claim 1, characterized in that: The process of calculating the mass ratio of large particle sediment to small particle sediment according to the calcium-phosphorus ratio and obtaining the mass according to the ratio for mixing is as follows: By formula The ratio of the required mass of large particle sedimentation to the required mass of small particle sedimentation is calculated; according to the ratio, the mass Mlarge of large particle sedimentation and the mass Msmall of small particle sedimentation are found within a reasonable range for mixing.

10. A highly active tricalcium phosphate, characterized in that: The high-activity tricalcium phosphate is prepared by the preparation process described in any one of claims 1 to 9.

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