CN106006593A - Simple and efficient preparation method of nano calcium phosphate - Google Patents
Simple and efficient preparation method of nano calcium phosphate Download PDFInfo
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- CN106006593A CN106006593A CN201610331543.0A CN201610331543A CN106006593A CN 106006593 A CN106006593 A CN 106006593A CN 201610331543 A CN201610331543 A CN 201610331543A CN 106006593 A CN106006593 A CN 106006593A
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- C01B25/00—Phosphorus; Compounds thereof
- C01B25/16—Oxyacids of phosphorus; Salts thereof
- C01B25/26—Phosphates
- C01B25/32—Phosphates of magnesium, calcium, strontium, or barium
- C01B25/325—Preparation by double decomposition
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Abstract
A simple and efficient preparation method of nano calcium phosphate comprises steps as follows: A, a calcium salt solution and a phosphate solution are prepared; B, diphosphonate is dissolved in the calcium salt solution, the phosphate solution is dropwise added to the calcium salt solution at the temperature of 37 DEG C, a reaction system is formed, and the pH value of the reaction system is adjusted to 7.0-11.0; the mole ratio of calcium to diphosphonate to phosphorus in the reaction system is (0.50-1.67): (0.01-0.02):1; after titration is completed, the reaction system is continuously stirred for 1-120 min, and the pH value of the reaction system is adjusted to 7.0-11.0; centrifugal washing and filtration are performed, precipitates are re-suspended in absolute ethyl alcohol, and a turbid liquid is obtained; C, a diphosphonate chemical is added to the turbid liquid, nano calcium phosphate slurry is obtained, and the mole ratio of diphosphonate to phosphorus in the nano calcium phosphate slurry is (0.01-0.02):1; the nano calcium phosphate slurry is subjected to ball milling treatment at the rotating speed of 300-600 r/min for 4-12 h and finally dried, and nano calcium phosphate powder is obtained.
Description
Technical field
The invention belongs to technical field of biomedical materials, be specifically related to a kind of simple and effective preparation nanometer phosphoric acid
The method of calcium.
Background technology
Calcium phosphate is the main inorganic composition of body bone and tooth, research find the ultrastructure of bone and tooth be all by
Nano-calcium phosphate is constituted, and nano-calcium phosphate to have skin effect, small-size effect and high reaction activity etc. all
The most special physicochemical property, nano-calcium phosphate attracts wide attention.At present nano-calcium phosphate mainly as
The pharmaceutical carrier of neoplasm targeted therapy and the genophore of medical diagnosis on disease, be simultaneously available for calcium phosphate artificial bone and prop up
The preparation of frame.The calcium phosphate support built has higher mechanical strength and excellent biology performance.Due to
Build calcium phosphate support and need substantial amounts of nano-calcium phosphate, it is therefore desirable to develop efficient, easy nanometer phosphoric acid
Calcium preparation method.
Existing nano-calcium phosphate preparation method is mainly wet method coprecipitation, i.e. by the Ca in solution2+With
PO4 3-Quick coprecipitation reaction is occurred to generate nanoscale calcium phosphate.Owing to its settling velocity is fast, calcium phosphate
Crystal nucleation and growth is difficult to control.Though can be by reducing Ca2+And PO4 3-Reaction density and the method for temperature
Reduce response speed and preferably control its crystal nucleation and growth；But reduce concentration and temperature can affect nanometer
Calcium phosphate productivity.Also the growth of nano-calcium phosphate crystal can be controlled by adding surfactant, but institute
The problem that the surfactant added may bring biocompatibility.Additionally, the calcium phosphate precipitation of Moist chemical synthesis
Dry run is also easily caused and forms the hard agglomeration of chemical bonding between granule (king looks for hall, Li Mei, Liu Zhao
Just etc. the Agglomeration Mechanism of superfine powder and sign and elimination. China's powder technology, 2008,14 (3): 46-51)；
By using lyophilization, the method for supercritical drying can avoid hard aggregation, cause again its preparation cost significantly
Improve.
Summary of the invention
It is an object of the invention to provide a kind of simple and effective nano-calcium phosphate preparation method, the product of this kind of method
Rate is high, the nano-calcium phosphate biocompatibility of preparation is high, good stability.
The present invention realizes its goal of the invention and be employed technical scheme comprise that, a kind of simple and effective nano-calcium phosphate
Preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Soluble calcium salt is dissolved in deionized water, obtains calcium salt soln；Soluble phosphate is dissolved in deionized water,
Obtain phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add diphosphonate, make diphosphonate be dissolved in calcium salt molten
In liquid；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln, with
Time make the pH value of reaction system be 7.0-11.0 by pH adjusting agent；After having titrated, calcium in reaction system,
Diphosphonate, the mol ratio of phosphorus are 0.50-1.67:0.01-0.02:1；
Continue stirring 0-120min after having titrated, and make reactant by pH adjusting agent while stirring
The pH value of system is maintained at 7.0-11.0；Stand 3-5 days subsequently, then wash through deionized water and dehydrated alcohol are centrifugal
Wash, filter, then precipitate is resuspended in dehydrated alcohol and obtains suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add biphosphonates to suspension and obtain nano-calcium phosphate slurry, double phosphines in nano-calcium phosphate slurry
Hydrochlorate is 0.01-0.02:1 with the mol ratio of phosphorus；It is 300-600 that nano-calcium phosphate slurry carries out rotary speed again
R/min, the time is the ball-milling treatment of 4-12h, is finally dried by nano-calcium phosphate slurry, obtains nanometer phosphoric acid
Calcium powder body.
The reaction mechanism of the present invention is:
Phosphonyl group in diphosphonate molecule and hydroxyl are all and Ca2+There is relatively strong affinity, receive at Moist chemical synthesis
Add diphosphonate during rice calcium phosphate, other PO can be suppressed4 3-With Ca2+Combination, generationization
Learn peptizaiton, it is to avoid by weak phases such as electrostatic attraction, Van der Waals force and Coulomb forces between nano-calcium phosphate granule
It is soft-agglomerated that interaction is formed, and stops the fast-growth of calcium phosphate crystal so that it is poor growth, PO4 3-Can be with
Ca2+Act on more fully, form more more stable nano-calcium phosphate granule.
During ball-milling treatment, nano-calcium phosphate particle generator machine ex tool activation and rupture, refine, enter
One step enhances the activity of nano-calcium phosphate granule；The diphosphonate simultaneously again added during ball-milling treatment
Molecule also produces above chemical dispersion effect, prevents the soft group of nano-calcium phosphate granule rupturing, refining
Poly-so that it is activity is maintained.And diphosphonate continues to produce chemical dispersion effect in dry run,
Nanoparticle is avoided to be formed by strong interactions such as capillary attraction, hydrogen bond and brilliant bridges in dry run
Serious hard aggregation, and then keep the activity of nano-calcium phosphate granule, it is achieved nano-calcium phosphate efficient, stable
Preparation.
Compared with prior art, the invention has the beneficial effects as follows:
One, by adding diphosphonate, diphosphonate during the Moist chemical synthesis nano-calcium phosphate of B step
Produce chemical dispersion effect, be i.e. avoided that formed between nano-calcium phosphate granule soft-agglomerated；Meanwhile, also make
PO4 3-Energy and Ca2+Act on more fully, form the most more stable nano-calcium phosphate granule, improve and receive
Rice calcium phosphate granules productivity and activity.
By the mechanical activation effect of the ball-milling treatment that C walks, make the nano-calcium phosphate of B step Moist chemical synthesis
Grain ruptures, refines, and further enhancing the activity of nano-calcium phosphate granule；Simultaneously ball-milling treatment during again
The diphosphonate molecule of secondary addition again prevent rupture, the nano-calcium phosphate granule that refines soft-agglomerated, make
Its activity is maintained；And in dry run, diphosphonate also may proceed to produce chemical dispersion effect, keeps away
Exempt from rice corpuscles hard aggregation in dry run, preferably to keep the activity of nano-calcium phosphate granule.
In a word, the yield of nano-calcium phosphate prepared by the present invention is big, efficiency is high, active strong, good stability.
Test shows, calcium phosphate granules size is 40～60nm, and Zeta potential is-15.0～16.0mV.
Two, the diphosphonate added is except having good chemical dispersion effect to calcium phosphate, can effectively control to receive
Outside the size of rice calcium phosphate, or a kind new medicine of the antimetabolic osteopathia grown up over nearly 20 years, face
Bed is for treating hypercalcemia and the osteodynia that osteoporosis, scleromalacia and malignant metastatic tumor of bone cause
Disease etc..Therefore, the present invention uses diphosphonate to substitute conventional surfactant, does not only reduce nanometer phosphorus
The biocompatibility of acid calcium, improves the biocompatibility of nano-calcium phosphate on the contrary, also improves nanometer simultaneously
The therapeutical effect of the bone support that calcium phosphate granules makes.
Three, the preparation method of the present invention is carried out under the temperate condition of liquid-phase system, reaction density is higher than existing
Wet method coprecipitation, its preparation method is simple, efficiency is high, beneficially large-scale production.
Further, the soluble calcium salt preparing calcium salt soln addition in step A of the present invention is four liquid glauber salt acid
Calcium (Ca (NO3)2·4H2Or calcium chloride (CaCl O)2)。
Both calcium salts be synthesis synthos conventional calcium salt, dissolubility is good, its anion to product without
Impact, easily removes.
Further, the soluble phosphate preparing phosphate solution addition in step A of the present invention is phosphoric acid
Hydrogen diammonium ((NH4)2HPO4), ammonium dihydrogen phosphate (NH4H2PO4), disodium hydrogen phosphate (Na2HPO4), phosphoric acid
Sodium dihydrogen (NaH2PO4), dipotassium hydrogen phosphate (K2HPO4) or potassium dihydrogen phosphate (KH2PO4)。
These several phosphate are the phosphate that synthesis synthos are conventional, and dissolubility is good, and its cation is to product
Thing, without impact, easily removes.
Further, when synthesizing nano-calcium phosphate in step B of the present invention, calcium with the mixing mol ratio of phosphorus is
0.50-1.67, the nano-calcium phosphate of synthesis includes unformed calcium phosphate (ACP), a water dalcium biphosphate
(MCPM), dicalcium phosphate dehydrate (DCPD), calcium hydrogen phosphate (DCPA), OCP (OCP), hydroxyl phosphorus
Lime stone (HA) and calcium deficiency apatite (CDHA).
Further, in step B of the present invention, available peristaltic pump controls phosphate solution titration calcium exactly
The speed of saline solution.
Further, step B of the present invention regulates the pH value of solution, make pH stable 7.0～10.0
PH value regulator used is: the NH of 0.1～1.0mol/L3·H2O solution.
Ammonia is alkalescence, and the pH that can regulate solution is alkalescence.Ammonia is weak electrolyte simultaneously, can keep away
Exempt from because of OH-Excessive concentration and form Ca (OH) in the product2, and easily remove.
With detailed description of the invention, the present invention is described further below in conjunction with the accompanying drawings.
Accompanying drawing explanation
Fig. 1 is that the X-ray diffractometer (XRD) preparing product in embodiment 3 characterizes collection of illustrative plates；
Fig. 2 is the scanning electron microscopic picture preparing product in embodiment 3；
Fig. 3 is the transmission electron microscope picture that embodiment 4 prepares product；
Fig. 4 is energy disperse spectroscopy (EDS) scanned picture that embodiment 4 prepares product.
Detailed description of the invention
Embodiment 1
A kind of simple and effective nano-calcium phosphate preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Four water-calcium nitrate is dissolved in deionized water, obtains calcium salt soln；By ammonium dihydrogen phosphate (NH4H2PO4) be dissolved in
Deionized water, obtains phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add neridronic acid sodium, make neridronic acid sodium be dissolved in calcium
In saline solution；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln,
Simultaneously by the NH of pH adjusting agent 0.1mol/L4OH solution, the pH value making reaction system is 7.0；
After having titrated, in reaction system, calcium, neridronic acid sodium, the mol ratio of phosphorus are 0.5:0.01:1；
Stirring 30min is continued after having titrated, and by pH adjusting agent 0.1mol/L while stirring
NH4OH solution makes the pH value of reaction system be maintained at 7.0；Stand 3 days subsequently, then through deionized water
With dehydrated alcohol centrifuge washing, filter, then precipitate is resuspended in dehydrated alcohol and obtains suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add neridronic acid sodium to suspension and obtain nano-calcium phosphate slurry, how nano-calcium phosphate slurry founds phosphine
Acid sodium is 0.01:1 with the mol ratio of phosphorus；It is 300r/min that nano-calcium phosphate slurry carries out rotary speed again,
Time is the ball-milling treatment of 4h, is finally dried by nano-calcium phosphate slurry, obtains nano-calcium phosphate powder body,
Nano-calcium phosphate is mainly composed of calcium superphosphate (MCPM).
Embodiment 2
A kind of simple and effective nano-calcium phosphate preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Four water-calcium nitrate is dissolved in deionized water, obtains calcium salt soln；By ammonium dihydrogen phosphate (NH4H2PO4) be dissolved in
Deionized water, obtains phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add olpadronic acid sodium, make olpadronic acid sodium be dissolved in calcium
In saline solution；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln,
Simultaneously by the NH of pH adjusting agent 0.1mol/L4OH solution, the pH value making reaction system is 8.0；
After having titrated, in reaction system, calcium, olpadronic acid sodium, the mol ratio of phosphorus are 1:0.01:1；
Stirring 120min is continued after having titrated, and by pH adjusting agent 0.1mol/L while stirring
NH4OH solution makes the pH value of reaction system be maintained at 8.0；Stand 4 days subsequently, then through deionized water
With dehydrated alcohol centrifuge washing, filter, then precipitate is resuspended in dehydrated alcohol and obtains suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add olpadronic acid sodium to suspension and obtain nano-calcium phosphate slurry, handkerchief phosphine difficult to understand in nano-calcium phosphate slurry
Acid sodium is 0.01:1 with the mol ratio of phosphorus；It is 400r/min that nano-calcium phosphate slurry carries out rotary speed again,
Time is the ball-milling treatment of 6h, is finally dried by nano-calcium phosphate slurry, obtains nano-calcium phosphate powder body,
Nano-calcium phosphate is mainly composed of dicalcium phosphate dehydrate (DCPD).
Embodiment 3
A kind of simple and effective nano-calcium phosphate preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Four water-calcium nitrate is dissolved in deionized water, obtains calcium salt soln；By disodium hydrogen phosphate (Na2HPO4) be dissolved in
Deionized water, obtains phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add Alendronate sodium, make Alendronate sodium be dissolved in calcium
In saline solution；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln,
Simultaneously by the NH of pH adjusting agent 1.0mol/L4OH solution, the pH value making reaction system is 11.0；
After having titrated, in reaction system, calcium, Alendronate sodium, the mol ratio of phosphorus are 1.67:0.02:1；
Stirring 30min is continued after having titrated, and by pH adjusting agent 1.0mol/L while stirring
NH4OH solution makes the pH value of reaction system be maintained at 11.0；Stand 5 days subsequently, then through deionization
Water and dehydrated alcohol centrifuge washing, filter, then precipitate be resuspended in dehydrated alcohol and obtain suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add Alendronate sodium to suspension and obtain nano-calcium phosphate slurry, A Lun phosphine in nano-calcium phosphate slurry
Acid sodium is 0.02:1 with the mol ratio of phosphorus；It is 600r/min that nano-calcium phosphate slurry carries out rotary speed again,
Time is the ball-milling treatment of 12h, is finally dried by nano-calcium phosphate slurry, obtains nano-calcium phosphate powder body.
The nano-calcium phosphate that this example prepares is mainly composed of hydroxyapatite (HA), and its XRD figure composes such as Fig. 1,
All samples diffraction maximum position is consistent with hydroxyapatite standard card, illustrates that the addition of diphosphonate will not shadow
Ring the thing phase composition of hydroxyapatite.Owing to diphosphonate can suppress hydroxylapatite crystal, therefore prepare
Hydroxylapatite crystal degree is relatively low, causes hydroxyapatite (3 0 0) crystallographic plane diffraction peak intensity relatively low, it is impossible to from
Figure is directly differentiated, therefore uses Gauss curve fitting method to isolate (3 0 0) crystallographic plane diffraction peak, and utilize Scherrer
Formula calculates the crystallite dimension (D of (3 0 0) and (0 0 2) crystal face(300)And D(002)) it is respectively 23.7nm and 18.9
Nm, in nanometer range.
Fig. 2 is the scanning electron microscopic picture of the nano-calcium phosphate that this example prepares, and Fig. 2 shows the nanometer phosphoric acid prepared
Calcium is needle bar shape, and length is in 30～100nm scopes, and diameter is in 10～30nm scopes.
Embodiment 4
A kind of simple and effective nano-calcium phosphate preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Calcium chloride is dissolved in deionized water, obtains calcium salt soln；By sodium dihydrogen phosphate (NaH2PO4) be dissolved in from
Sub-water, obtains phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add Alendronate sodium, make Alendronate sodium be dissolved in calcium
In saline solution；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln,
Simultaneously by the NH of pH adjusting agent 1.0mol/L4OH solution, the pH value making reaction system is 9.0；
After having titrated, in reaction system, calcium, Alendronate sodium, the mol ratio of phosphorus are 1.67:0.01:1；
Stirring 30min is continued after having titrated, and by pH adjusting agent 1.0mol/L while stirring
NH4OH solution makes the pH value of reaction system be maintained at 9.0；Stand 4 days subsequently, then through deionized water
With dehydrated alcohol centrifuge washing, filter, then precipitate is resuspended in dehydrated alcohol and obtains suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add Alendronate sodium to suspension and obtain nano-calcium phosphate slurry, A Lun phosphine in nano-calcium phosphate slurry
Acid sodium is 0.01:1 with the mol ratio of phosphorus；It is 600r/min that nano-calcium phosphate slurry carries out rotary speed again,
Time is the ball-milling treatment of 12h, is finally dried by nano-calcium phosphate slurry, obtains nano-calcium phosphate powder body.
The calcium phosphate that this example prepares is mainly composed of hydroxyapatite (HA), its transmission electron microscope picture such as Fig. 3.
Fig. 3 shows, adds Alendronate sodium and mechanical activation processes, and aggregate structure is broken, and prepares the pin of thing
Rod-like nano calcium phosphate structure is relatively decentralized.
Fig. 4 is the EDX scanned picture that this example prepares thing, and Ca element and P element are from hydroxyl as seen from Figure 4
Base apatite, Ti element is from substrate.Synthesis and mechanical activation all add Alendronate sodium when processing, but
Addition is less, and therefore Fig. 4 only demonstrates fainter Na element spectral peak, but provable Alendronate sodium
Do exist in prepared thing.
Embodiment 5
A kind of simple and effective nano-calcium phosphate preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Calcium chloride is dissolved in deionized water, obtains calcium salt soln；By dipotassium hydrogen phosphate (K2HPO4) it is dissolved in deionization
Water, obtains phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add risedronate sodium, make risedronate sodium be dissolved in calcium
In saline solution；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln,
Simultaneously by the NH of pH adjusting agent 1.0mol/L4OH solution, the pH value making reaction system is 7.0；
After having titrated, in reaction system, calcium, risedronate sodium, the mol ratio of phosphorus are 1.5:0.01:1；
Stirring 60min is continued after having titrated, and by pH adjusting agent 1.0mol/L while stirring
NH4OH solution makes the pH value of reaction system be maintained at 9.0；Stand 4 days subsequently, then through deionized water
With dehydrated alcohol centrifuge washing, filter, then precipitate is resuspended in dehydrated alcohol and obtains suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add risedronate sodium to suspension and obtain nano-calcium phosphate slurry, profit plug phosphine in nano-calcium phosphate slurry
Acid sodium is 0.01:1 with the mol ratio of phosphorus；It is 400r/min that nano-calcium phosphate slurry carries out rotary speed again,
Time is the ball-milling treatment of 10h, is finally dried by nano-calcium phosphate slurry, obtains nano-calcium phosphate powder body,
Calcium phosphate is mainly composed of unformed calcium phosphate (ACP).
Embodiment 6
A kind of simple and effective nano-calcium phosphate preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Calcium chloride is dissolved in deionized water, obtains calcium salt soln；By potassium dihydrogen phosphate (KH2PO4) it is dissolved in deionization
Water, obtains phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add ibandronic acid sodium, make ibandronic acid sodium be dissolved in calcium
In saline solution；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln,
Simultaneously by the NH of pH adjusting agent 1.0mol/L4OH solution, the pH value making reaction system is 9.0；
After having titrated, in reaction system, calcium, ibandronic acid sodium, the mol ratio of phosphorus are 1.33:0.01:1；
Stirring 30min is continued after having titrated, and by pH adjusting agent 1.0mol/L while stirring
NH4OH solution makes the pH value of reaction system be maintained at 7.0；Stand 3 days subsequently, then through deionized water
With dehydrated alcohol centrifuge washing, filter, then precipitate is resuspended in dehydrated alcohol and obtains suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add ibandronic acid sodium to suspension and obtain nano-calcium phosphate slurry, her this phosphine in nano-calcium phosphate slurry
Acid sodium is 0.01:1 with the mol ratio of phosphorus；It is 400r/min that nano-calcium phosphate slurry carries out rotary speed again,
Time is the ball-milling treatment of 10h, is finally dried by nano-calcium phosphate slurry, obtains nano-calcium phosphate powder body,
Nano-calcium phosphate is mainly composed of OCP (OCP).
Embodiment 7
A kind of simple and effective nano-calcium phosphate preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Four water-calcium nitrate is dissolved in deionized water, obtains calcium salt soln；By diammonium phosphate ((NH4)2HPO4) molten
In deionized water, obtain phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add Alendronate sodium, make Alendronate sodium be dissolved in calcium
In saline solution；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln,
Simultaneously by the NH of pH adjusting agent 1.0mol/L4OH solution, the pH value making reaction system is 7.0；
After having titrated, calcium, diammonium phosphate ((NH in reaction system4)2HPO4), the mol ratio of phosphorus be 1:0.01:1；
Stirring 30min is continued after having titrated, and by pH adjusting agent 1.0mol/L while stirring
NH4OH solution makes the pH value of reaction system be maintained at 7.0；Stand 4 days subsequently, then through deionized water
With dehydrated alcohol centrifuge washing, filter, then precipitate is resuspended in dehydrated alcohol and obtains suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add ibandronic acid sodium to suspension and obtain nano-calcium phosphate slurry, her this phosphine in nano-calcium phosphate slurry
Acid sodium is 0.01:1 with the mol ratio of phosphorus；It is 400r/min that nano-calcium phosphate slurry carries out rotary speed again,
Time is the ball-milling treatment of 10h, is finally dried by nano-calcium phosphate slurry, obtains nano-calcium phosphate powder body,
Nano-calcium phosphate is mainly composed of a water calcium hydrogen phosphate (DCPA).
Embodiment 8
A kind of simple and effective nano-calcium phosphate preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Four water-calcium nitrate is dissolved in deionized water, obtains calcium salt soln；By diammonium phosphate ((NH4)2HPO4) molten
In deionized water, obtain phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add Alendronate sodium, make Alendronate sodium be dissolved in calcium
In saline solution；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln,
Simultaneously by the NH of pH adjusting agent 1.0mol/L4OH solution, the pH value making reaction system is 10.0；
After having titrated, calcium, diammonium phosphate ((NH in reaction system4)2HPO4), the mol ratio of phosphorus be
1.6:0.01:1；
Stirring 30min is continued after having titrated, and by pH adjusting agent 1.0mol/L while stirring
NH4OH solution makes the pH value of reaction system be maintained at 8.0；Stand 4 days subsequently, then through deionized water
With dehydrated alcohol centrifuge washing, filter, then precipitate is resuspended in dehydrated alcohol and obtains suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add ibandronic acid sodium to suspension and obtain nano-calcium phosphate slurry, her this phosphine in nano-calcium phosphate slurry
Acid sodium is 0.01:1 with the mol ratio of phosphorus；It is 400r/min that nano-calcium phosphate slurry carries out rotary speed again,
Time is the ball-milling treatment of 10h, is finally dried by nano-calcium phosphate slurry, obtains nano-calcium phosphate powder body,
Calcium phosphate is mainly composed of calcium-deficient apatite (CDHA).
Claims (5)
1. a simple and effective nano-calcium phosphate preparation method, the steps include:
A, prepare calcium salt soln and phosphate solution:
Soluble calcium salt is dissolved in deionized water, obtains calcium salt soln；Soluble phosphate is dissolved in deionized water,
Obtain phosphate solution；
B, Moist chemical synthesis nano-calcium phosphate:
Under magnetic agitation effect, in calcium salt soln, add diphosphonate, make diphosphonate be dissolved in calcium salt molten
In liquid；Again under 37 DEG C of temperature conditionss, phosphate solution is instilled formation reaction system in calcium salt soln, with
Time make the pH value of reaction system be 7.0-11.0 by pH adjusting agent；Calcium in reaction system, diphosphonate,
The mol ratio of phosphorus is 0.50～1.67:0.01～0.02:1；
After having titrated, continue stirring 0～120min, and made instead by pH adjusting agent while stirring
The pH value answering system is maintained at 7.0～11.0；Stand 3-5 days subsequently, then through deionized water and dehydrated alcohol
Centrifuge washing, filters, then precipitate is resuspended in dehydrated alcohol and obtains suspension；
C, mechanical activation combine chemical dispersion and prepare nano-calcium phosphate:
Add biphosphonates to suspension and obtain nano-calcium phosphate slurry, double phosphines in nano-calcium phosphate slurry
Hydrochlorate is 0.01～0.02:1 with the mol ratio of phosphorus；Again nano-calcium phosphate slurry being carried out rotary speed is
300～600r/min, the time is the ball-milling treatment of 4～12h, is finally dried by nano-calcium phosphate slurry, to obtain final product
Nano-calcium phosphate powder body.
Nano-calcium phosphate preparation method the most according to claim 1, it is characterised in that；Described step A
Soluble calcium salt be four water-calcium nitrate (Ca (NO3)2·4H2Or calcium chloride (CaCl O)2)。
Nano-calcium phosphate preparation method the most according to claim 1, it is characterised in that；Described step A
Soluble phosphate be diammonium phosphate ((NH4)2HPO4), disodium hydrogen phosphate (Na2HPO4), phosphoric acid hydrogen two
Potassium (K2HPO4), sodium dihydrogen phosphate (NaH2PO4), potassium dihydrogen phosphate (KH2PO4) or ammonium dihydrogen phosphate
(NH4H2PO4)。
Nano-calcium phosphate preparation method the most according to claim 1, it is characterised in that；Described step B
In the NH that pH value regulator is 0.1～1.0mol/L4OH solution.
Nano-calcium phosphate preparation method the most according to claim 1, it is characterised in that；Described step B
Middle diphosphonate is Alendronate sodium, neridronic acid sodium, olpadronic acid sodium, risedronate sodium or ibandronic acid
Sodium.
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| CN111138186A (en) * | 2020-01-09 | 2020-05-12 | 山东大学 | α tricalcium phosphate biological ceramic material and preparation method thereof |
| CN112499607A (en) * | 2020-10-29 | 2021-03-16 | 南京师范大学 | Preparation method of nano calcium phosphate for enrichment of polyphosphate peptide and identification of phosphorylation sites, product and application thereof |
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| CN114349786A (en) * | 2021-12-28 | 2022-04-15 | 中国科学院上海硅酸盐研究所 | Alendronate calcium ultralong nanowire and preparation method and application thereof |
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