CN108439360A - A kind of preparation method of spherical porous nanometer hydroxyapatite - Google Patents
A kind of preparation method of spherical porous nanometer hydroxyapatite Download PDFInfo
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Abstract
The invention discloses a kind of preparation methods of spherical porous nanometer hydroxyapatite, include the following steps：Prepare reaction solution (NH4)2HPO4Solution, template, salpeter solution and calcium and magnesium solution, by above-mentioned (NH4)2HPO4Solution is first placed in hydro-thermal reaction container, template and calcium and magnesium solution are added under stirring condition, then above-mentioned hydro-thermal reaction container is placed at reaction kettle is 180 DEG C in temperature after reacting 3 10h and is post-processed, solids is placed in crucible again and is placed in tube furnace, it is gradually heating to 500 700 DEG C, calcine natural cooling after 5 10h, i.e., spherical porous nanometer hydroxyapatite；Product made from preparation method through the invention is porous, good fluidity, large specific surface area, non-stimulated and safe.
Description
Technical field
The present invention relates to a kind of preparation methods of hydroxyapatite, and in particular to a kind of spherical porous nano-hydroxy-apatite
The preparation method of stone.
Background technology
Hydroxyapatite (hydroxyapatite, HAP) be vertebrate skeletal and tooth host inorganic mineral at
Point.Artificial synthesized hydroxyapatite have good biocompatibility, bioactivity, osteoconductive and its with natural bone mine
The similitude of object phase component is now widely used in organizational project, the reparation of bone and replacement and dental material etc..
The spherical nano-particles of HAP can not only protect drug molecule from the destruction of vivo environment as pharmaceutical carrier, and
And the modification of ligand molecular surface or functionalization targeted drug can be suitble to act on sick cell or tissue.Relative to aspherical HAP
Particle, HAP micro-sphere materials have many advantages, such as good fluidity, large specific surface area, are not easy to reunite, are easy to absorb in vivo,
Drug release, function absorption and bio-separation medium etc. have broad application prospects.
The report prepared about micron order, submicron order, nano-level sphere and hollow sphere HAP at present, however it is right
Report prepared by spherical porous nano-HAP is less.The study found that the grain size of HAP is smaller, the stretch modulus of bone implant, torsion
Modulus and tensile strength will be higher, and fatigue resistance also can be improved accordingly.Nowadays the preparation method of nanometer hydroxyapatite has
It is a variety of, such as hydro-thermal method, coprecipitation, sol-gel method, microemulsion method, biomineralization method, microwave solid source, method is burnt naturally
Deng.The characteristics of hydro-thermal method produces is that product is reunited less, and epigranular, purity is high, and production cost is low；But existing hydro-thermal legal system
The nanometer hydroxyapatite size obtained is larger, and spheroidal state is not added with, poor fluidity, and as pharmaceutical carrier, there is also larger to change
Into space.
Invention content
The porous nano hydroxyapatite that the purpose of the present invention is to provide a kind of spheroidal states is complete, mobility is good
Preparation method.
To achieve the goals above, the technical solution adopted by the present invention is：
A kind of preparation method of spherical porous nanometer hydroxyapatite specifically includes the following steps：
(1) reaction solution is prepared, including：(NH4)2HPO4Solution, template, salpeter solution and calcium and magnesium solution, wherein described
(NH4)2HPO4A concentration of 0.05-0.3mol/L of solution；A concentration of 2mol/L of the salpeter solution；The calcium and magnesium solution is
Ca(NO3)2.4H2O solution and MgCl2.6H2The mixed liquor of O solution；The wherein described Ca (NO3)2.4H2O solution it is a concentration of
0.01-0.03g/mL, the MgCl2.6H2A concentration of 0.0066-0.0187g/ml of O solution；
(2) by above-mentioned (NH4)2HPO4Solution is first placed in hydro-thermal reaction container, is added template under stirring condition, is waited for
(NH4)2HPO4Solution is uniformly mixed with template, and above-mentioned calcium and magnesium solution is added in continuation under agitation, and above-mentioned nitric acid is used in combination
Solution adjusts pH=5.1, wherein (the NH4)2HPO4The volume ratio of solution and calcium and magnesium solution is 100:167；It then will be above-mentioned
Hydro-thermal reaction container containing reaction solution is placed in reaction kettle, and 180 DEG C are gradually heating in Muffle furnace, and it is 180 DEG C to keep temperature
After lower reaction 3-10h, Temperature fall；
(3) the mixture centrifugation after reaction in step (2) is removed into supernatant, solids centrifuges again wash with distilled water
Supernatant is removed, is recycled 4-8 times, until supernatant PH>7, by the remaining solid object after removal supernatant in the sky no more than 60 DEG C
Compression ring is dried under border；Then it is placed in crucible and is placed in tube furnace, be gradually heating to 500-700 DEG C, calcine nature after 5-10h
It is cooling, solid powder is obtained, i.e., spherical porous nanometer hydroxyapatite.
Further, the described (NH4)2HPO4A concentration of 0.1mol/L of solution.
Further, the template is one or more kinds of in gelatin, xanthans, sodium alginate or Glucomannan
Aqueous solution.
Further, the template be 0.12%wt aqueous gelatin solution, and institute's gelatin water solution with it is described
(NH4)2HPO4The volume ratio of solution is 23:20.
Further, in the calcium and magnesium solution, the Ca (NO3)2.4H2A concentration of 0.02361g/mL of O solution, it is described
MgCl2.6H2A concentration of 0.01794g/ml of O solution.
Further, in step (2), the NaHCO of 0.01-0.2%wt is added before adjusting pH=5.13Solution, and it is described
NaHCO3Solution and the (NH4)2HPO4The volume ratio of solution is 1-2:20.
Further, in step (3), the calcining temperature-rise period includes following three steps：A) the heating of 5 DEG C/min
Speed, control solids handle 2h in the air environment not higher than 200 DEG C；B) the heating rate of 5 DEG C/min controls solid
Object handles 3-8h in 500-560 DEG C of ar gas environment；C) cooled to room temperature.
Further, in step (3), the calcining temperature-rise period includes following three steps：A) the liter of 5 DEG C/min
Warm speed, control solids handle 2h in the air environment not higher than 200 DEG C；B) the heating rate of 5 DEG C/min, control are solid
Body object handles 3-8h in 560-600 DEG C of ar gas environment；C) cooled to room temperature.
Further, in step (3), the calcining temperature-rise period includes following three steps：A) the liter of 5 DEG C/min
Warm speed, control solids handle 2h in the air environment not higher than 200 DEG C；B) the heating rate of 5 DEG C/min, control are solid
Body object handles 3-8h in 600-700 DEG C of ar gas environment；C) cooled to room temperature.
Compared with prior art, the beneficial effects of the present invention are：
Complete by spherical porous nanometer hydroxyapatite spherical morphology made from the above method, mobility is good, specific surface
Product is big, non-stimulated, safe, the load suitable for biopharmaceutical macromolecular drugs such as protein, polypeptide, immunomodulator, vaccines
Body；In addition it can make full use of its porosity characteristic regulating medicine from the rate of release in carrier inside duct.
Description of the drawings
Fig. 1 is the SEM shape appearance figures of spherical porous nanometer hydroxyapatite in embodiment 3；
Fig. 2 is the TEM detection figures of spherical porous nanometer hydroxyapatite in embodiment 3；
Fig. 3 is the preceding infrared spectrogram with after calcining of the calcining of product containing magnesium；
Fig. 4 is the infrared spectrogram after the calcining of no magnesium product；
Fig. 5 is the XRD spectrum of spherical porous nanometer hydroxyapatite in embodiment 3；
Fig. 6 is the XRD spectrum that spherical porous nanometer hydroxyapatite product is prepared using different templates agent, wherein 1. for
Sodium alginate-hydroxyapatite；2. being glutin-hydroxyapatite；3. being glutin-hydroxyapatite/Mg；
Fig. 7 is spherical porous nanometer hydroxyapatite porosity and N in embodiment 22Adsorption-desorption analysis report；
Fig. 8 is the porosity and N of commercially available medicinal montmorillonite KSF2Adsorption-desorption analysis report.
Specific implementation mode
The present invention is described in detail below in conjunction with the accompanying drawings.
Embodiment 1
A kind of preparation method of spherical porous nanometer hydroxyapatite specifically includes the following steps：
(1) reaction solution is prepared, including：(NH4)2HPO4Solution, template, salpeter solution and calcium and magnesium solution, wherein
(NH4)2HPO4A concentration of 0.05mol/L of solution；Template be 0.12%wt aqueous gelatin solution, and with (NH4)2HPO4It is molten
The volume ratio of liquid is 23:20；A concentration of 2mol/L of salpeter solution；Calcium and magnesium solution is Ca (NO3)2.4H2O solution and
MgCl2.6H2The mixed liquor of O solution, and Ca (NO3) 2.4H2A concentration of 0.01g/mL, MgCl of O solution2.6H2O solution it is dense
Degree is 0.0066g/ml.
(2) by above-mentioned (NH4)2HPO4Solution is first placed in hydro-thermal reaction container, is added template under stirring condition, is waited for
(NH4)2HPO4Solution is uniformly mixed with template, and above-mentioned calcium and magnesium solution is added in continuation under agitation, adds 0.01%
The NaHCO of wt3Solution, and with (NH4)2HPO4The volume ratio of solution is 1:20；It is used in combination above-mentioned salpeter solution to adjust pH=5.1,
Wherein, (NH4)2HPO4The volume ratio of solution and calcium and magnesium solution is 100:167；Then by above-mentioned, the hydro-thermal reaction containing reaction solution is held
Device is placed in reaction kettle, and 180 DEG C are gradually heating in Muffle furnace, and it is Temperature fall at 180 DEG C after reaction 5h to keep temperature；
(3) the mixture centrifugation after reaction in step (2) is removed into supernatant, solids centrifuges again wash with distilled water
Supernatant is removed, is recycled 6 times, until supernatant PH>7, by the remaining solid object after removal supernatant in the air no more than 60 DEG C
It is dried under environment；Then it is placed in crucible and is placed in calcining in tube furnace, temperature reaction process includes following three steps：A)5
DEG C/heating rate of min, control solids handles 2h in the air environment not higher than 200 DEG C；B) the heating speed of 5 DEG C/min
Degree, control solids handle 3h in 500-560 DEG C of ar gas environment；C) cooled to room temperature；Solid powder is obtained, i.e.,
Spherical porous nanometer hydroxyapatite.
By carrying out porosity and N to above-mentioned spherical porous nanometer hydroxyapatite product2Adsorption-desorption is analyzed, and table is compared
Area is 61.7239m2/ g, comparison are less than using nano-HAP sample specific surface area of the identical synthetic method through relatively low heat treatment
20m2/ g, and the medicinal montmorillonite KSF specific surface areas of abundant bio tech ltd of common product Hisense as above are on the market
20-40m2/ g, it can be seen that the spherical porous nanometer hydroxyapatite porous character prepared through the above method is notable, is more suitable for
As pharmaceutical carrier.
Embodiment 2
A kind of preparation method of spherical porous nanometer hydroxyapatite specifically includes the following steps：
(1) reaction solution is prepared, including：(NH4)2HPO4Solution, template, salpeter solution and calcium and magnesium solution, wherein
(NH4)2HPO4A concentration of 0.3mol/L of solution；Template be 0.12%wt xanthan gum solution, and with (NH4)2HPO4It is molten
The volume ratio of liquid is 23:20；A concentration of 2mol/L of salpeter solution；Calcium and magnesium solution is Ca (NO3)2.4H2O solution and
MgCl2.6H2The mixed liquor of O solution, and Ca (NO3) 2.4H2A concentration of 0.03g/mL, MgCl of O solution2.6H2O solution it is dense
Degree is 0.0187g/ml.
(2) by above-mentioned (NH4)2HPO4Solution is first placed in hydro-thermal reaction container, is added template under stirring condition, is waited for
(NH4)2HPO4Solution is uniformly mixed with template, and above-mentioned calcium and magnesium solution is added in continuation under agitation, and above-mentioned nitric acid is used in combination
Solution adjusts pH=5.1, wherein (NH4)2HPO4The volume ratio of solution and calcium and magnesium solution is 100:167；Then by above-mentioned containing anti-
It answers the hydro-thermal reaction container of liquid to be placed in reaction kettle, 180 DEG C is gradually heating in Muffle furnace, it is anti-at 180 DEG C to keep temperature
After answering 5h, Temperature fall；
(3) the mixture centrifugation after reaction in step (2) is removed into supernatant, solids centrifuges again wash with distilled water
Supernatant is removed, is recycled 4 times, until supernatant PH>7, by the remaining solid object after removal supernatant in the air no more than 60 DEG C
It is dried under environment；Then it is placed in crucible and is placed in calcining in tube furnace, temperature reaction process includes following three steps：A)5
DEG C/heating rate of min, control solids handles 2h in the air environment not higher than 200 DEG C；B) the heating speed of 5 DEG C/min
Degree, control solids handle 8h in 560-600 DEG C of ar gas environment；C) cooled to room temperature；Solid powder is obtained, i.e.,
Spherical porous nanometer hydroxyapatite.
By carrying out porosity and N to above-mentioned spherical porous nanometer hydroxyapatite product2Adsorption-desorption is analyzed, and table is compared
Area is 43.4627m2/ g, comparison are less than using nano-HAP sample specific surface area of the identical synthetic method through relatively low heat treatment
20m2/ g, and the medicinal montmorillonite KSF specific surface areas of abundant bio tech ltd of common product Hisense as above are on the market
20-40m2/ g, it can be seen that the spherical porous nanometer hydroxyapatite porous character prepared through the above method is notable, is more suitable for
As pharmaceutical carrier.
Embodiment 3
A kind of preparation method of spherical porous nanometer hydroxyapatite specifically includes the following steps：
(1) reaction solution is prepared, including：(NH4)2HPO4Solution, template, salpeter solution and calcium and magnesium solution, wherein
(NH4)2HPO4A concentration of 0.1mol/L of solution；Template be 0.12%wt sodium alginate aqueous solution, and with (NH4)2HPO4The volume ratio of solution is 23:20；A concentration of 2mol/L of salpeter solution；Calcium and magnesium solution is Ca (NO3)2.4H2O solution and
MgCl2.6H2The mixed liquor of O solution, and Ca (NO3)2.4H2A concentration of 0.02g/mL, MgCl of O solution2.6H2O solution it is dense
Degree is 0.0105g/ml.
(2) by above-mentioned (NH4)2HPO4Solution is first placed in hydro-thermal reaction container, is added template under stirring condition, is waited for
(NH4)2HPO4Solution is uniformly mixed with template, and above-mentioned calcium and magnesium solution is added in continuation under agitation, and above-mentioned nitric acid is used in combination
Solution adjusts pH=5.1, wherein (NH4)2HPO4The volume ratio of solution and calcium and magnesium solution is 100:167；Then by above-mentioned containing anti-
It answers the hydro-thermal reaction container of liquid to be placed in reaction kettle, 180 DEG C is gradually heating to 1 DEG C/min in Muffle furnace, holding temperature is
After 5h being reacted at 180 DEG C, Temperature fall；
(3) the mixture centrifugation after reaction in step (2) is removed into supernatant, solids centrifuges again wash with distilled water
Supernatant is removed, is recycled 8 times, until supernatant PH>7, by the remaining solid object after removal supernatant in the air no more than 60 DEG C
It is dried under environment；Then it is placed in crucible and is placed in calcining in tube furnace, temperature reaction process includes following three steps：A)5
DEG C/heating rate of min, control solids handles 2h in the air environment not higher than 200 DEG C；B) the heating speed of 5 DEG C/min
Degree, control solids handle 5h in 600-700 DEG C of ar gas environment；C) cooled to room temperature；Solid powder is obtained, i.e.,
Spherical porous nanometer hydroxyapatite.
By carrying out porosity and N to above-mentioned spherical porous nanometer hydroxyapatite product2Adsorption-desorption is analyzed, and table is compared
Area is 65.1259m2/ g, comparison is using nano-HAP sample of the identical synthetic method through relatively low heat treatment (being not higher than 500 DEG C)
Specific surface area is less than 20m2/ g, and the medicinal montmorillonite of abundant bio tech ltd of common product Hisense as above on the market
KSF specific surface areas are 20-40m2/ g, it can be seen that the porous spy of spherical porous nanometer hydroxyapatite prepared through the above method
Sign is notable, is more suitable for pharmaceutical carrier.
The spherical porous nanometer hydroxyapatite further prepared to embodiment 3 is scanned Electronic Speculum, transmission electron microscope, red
External spectrum and XRD analysis are as shown in attached drawing 1-5.
It is apparent that prepared product morphology is spherical shape HAP particles from attached drawing 1, can be seen that particle in conjunction with attached drawing 2
Grain size is about 20-60nm, and sphere structure is complete.
Referring to infrared (FTIR) spectrum analyses of attached drawing 3-4, from attached drawing 3 as can be seen that 560cm-1、605cm-1、 1024cm-1、1078cm-1The absorption peak at place is PO4 3-Characteristic absorption peak, wherein 560cm-1Corresponding PO4 3-γ 4 vibration absorption peak,
1025cm-1Corresponding PO4 3-γ 3 vibration absorption peak, 2935cm-1For-CH2Stretching vibration peak, 1422cm-1For CO3 2-'s
Characteristic absorption peak, the two peaks illustrate that gelatin has doping to enter, 3435cm-1For OH-1Characteristic absorption peak；By product in 600-
It is as shown in Fig. 3 that 5h is calcined at 700 DEG C, it can be found that 2934cm-1The absorption peak at place, which is split, is divided into 2912cm-1And 2835cm-1,
It is the antisymmetry and symmetrical stretching vibration absorption peak of methyl and methylene, illustrates that product still contains carbon after calcining.This be because
After heat treatment for the nano-HAP solids that is prepared using gelatin or sodium alginate as template agent, solids appearance is in different journeys
The grey black of degree, and 2 θ values are that the intensity in 10~20 ranges is relatively high in corresponding XRD diagram, are carbonized with template agent in sample
Correlation, the presence of carbon have the load conducive to oil-soluble medicine.
Referring to attached drawing 5, diffraction peak intensity is high from collection of illustrative plates, magnesium ion known to sharp and narrow and symmetrical etc. features and calcium from
Son co-precipitation forms nanometer hydroxyapatite, and crystallization degree is high, is not the simple blend of a variety of precipitations, is adding appropriate magnesium salts
Synthetic system in, be conducive to synthesizing spherical porous nano hydroxyapatite (n-HAP), illustrate be nucleated derivant magnesium salts change
Crystal nucleation and growth mechanism not only influence size, the pattern of n-HAP, but also the collection of illustrative plates of XRD is significantly different；It further illustrates
It is changed using the Mechanism of kernel-forming and growth of n-HAP after magnesium salts.
Referring to attached drawing 6, wherein be 1. sodium alginate-hydroxyapatite；2. being glutin-hydroxyapatite；3. being gelatin-
Hydroxyapatite/Mg.Comparison is with reference to Ca10(PO4)6(OH)2The standard PDF cards of (JCPDS, NO.74-0566), it can be seen that 1.
2. each diffraction maximum is corresponded with the standard spectrogram of hydroxyapatite substantially in the XRD spectrum after two kinds of product calcinings, illustrate institute
Product obtained be HAP, be located at 2 θ=31.765 °, 32.896 °, 32.194 °, 25.882 °, 49.489 °, 46.693 °,
Diffraction maximum at 34.062 °, 39.790 ° is that HAP is located at (211) respectively, (300), (112), (002), (213), (222),
(202), the characteristic diffraction peak of (130) crystal face.Compared with gelatine system (2.), gelatine system obtains sodium alginate system (1.)
Uniform corynebacterium hydroxyapatite XRD spectra and standard card (JCPDS, NO.74-0566) it is corresponding preferable, and peak shape is sharp
Clearly；Sodium alginate system occur compared with standard card it is small move to left, be system in sodium alginate in the reaction be used as crystalline substance
Caused by body growth regulator.
With reference to Ca19.68Mg0.12H1.8(PO4)13.8The standard card of (JCPDS, NO.79-2186), it can be seen that 3. product is forged
Mainly with Mg in XRD spectrum after burning2+The compound Ca of doping19.68Mg0.12H1.8(PO4)13.8Form exists, and illustrates Mg2+
In compound be used as nucleating agent, be located at 2 θ=31.221 °, 34.604 °, 27.985 °, 53.303 °, 47.291 °, 32.663 ° points
It is not that the compound is located at (0210), (220), (214), (1010), (2020), the characteristic diffraction peak of (128) crystal face, and produce
Object spectrogram peak and Ca19.68Mg0.12H1.8(PO4)13.8(JCPDS, NO.79-2186) standard card is small compared to generation to move to left.It is right
The TEM of attached drawing 2 is answered to scheme, it can be seen that HAP products obtained by glutin-hydroxyapatite/Mg systems are nanometer porous spherical HAP.
Embodiment 4
A kind of preparation method of spherical porous nanometer hydroxyapatite specifically includes the following steps：
(1) reaction solution is prepared, including：(NH4)2HPO4Solution, template, salpeter solution and calcium and magnesium solution, wherein
(NH4)2HPO4A concentration of 0.2mol/L of solution；Template is the aqueous solution of the sodium alginate and Glucomannan of 0.12%wt,
And with (NH4)2HPO4The volume ratio of solution is 23:20；A concentration of 2mol/L of salpeter solution；Calcium and magnesium solution is Ca (NO3)2.4H2O solution and MgCl2.6H2The mixed liquor of O solution, and Ca (NO3)2.4H2A concentration of 0.02361g/mL of O solution,
MgCl2.6H2A concentration of 0.01794g/ml of O solution.
(2) by above-mentioned (NH4)2HPO4Solution is first placed in hydro-thermal reaction container, is added template under stirring condition, is waited for
(NH4)2HPO4Solution is uniformly mixed with template, and above-mentioned calcium and magnesium solution is added in continuation under agitation, adds 0.2%wt
NaHCO3Solution, and with (NH4)2HPO4The volume ratio of solution is 1:20 and with above-mentioned salpeter solution adjust pH=5.1,
In, (NH4)2HPO4The volume ratio of solution and calcium and magnesium solution is 100:167；Then the hydro-thermal reaction container containing reaction solution by above-mentioned
It is placed in reaction kettle, 180 DEG C is gradually heating to 1 DEG C/min in Muffle furnace, it is at 180 DEG C after reaction 5h, certainly to keep temperature
So cooling；
(3) the mixture centrifugation after reaction in step (2) is removed into supernatant, solids centrifuges again wash with distilled water
Supernatant is removed, is recycled 6 times, until supernatant PH>7, by the remaining solid object after removal supernatant in the air no more than 60 DEG C
It is dried under environment；Then it is placed in crucible and is placed in calcining in tube furnace, temperature reaction process includes following three steps：A)5
DEG C/heating rate of min, control solids handles 2h in the air environment not higher than 200 DEG C；B) the heating speed of 5 DEG C/min
Degree, control solids handle 3h in 560-600 DEG C of ar gas environment；C) cooled to room temperature；Solid powder is obtained, i.e.,
Spherical porous nanometer hydroxyapatite.
By carrying out porosity and N to above-mentioned spherical porous nanometer hydroxyapatite product2Adsorption-desorption is analyzed, and table is compared
Area is 55.1015m2/ g, comparison is using nano-HAP sample of the identical synthetic method through relatively low heat treatment (being not higher than 500 DEG C)
Specific surface area is less than 20m2/ g, and the medicinal montmorillonite of abundant bio tech ltd of common product Hisense as above on the market
KSF specific surface areas are 20-40m2/ g, it can be seen that the porous spy of spherical porous nanometer hydroxyapatite prepared through the above method
Sign is notable, is more suitable for pharmaceutical carrier.
The foregoing is merely the preferred embodiment of the present invention, are not intended to restrict the invention, for people in the art
For member, the invention may be variously modified and varied.All any modifications in spirit of that invention and principle, made are equal
Replace, improve etc., it should all be included in the protection scope of the present invention.
Claims (9)
1. a kind of preparation method of spherical porous nanometer hydroxyapatite, which is characterized in that include the following steps：
(1) reaction solution (NH is prepared4)2HPO4Solution, template, salpeter solution and calcium and magnesium the solution, wherein (NH4)2HPO4It is molten
A concentration of 0.05-0.3mol/L of liquid；A concentration of 2mol/L of the salpeter solution；The calcium and magnesium solution is Ca (NO3)2.4H2O
Solution and MgCl2.6H2The mixed liquor of O solution；The wherein described Ca (NO3)2.4H2A concentration of 0.01-0.03g/mL of O solution, institute
State MgCl2.6H2A concentration of 0.0066-0.0187g/ml of O solution；
(2) (the NH by described in4)2HPO4Solution is placed in hydro-thermal reaction container, and the template is added under stirring condition and is mixed equal
Even, the calcium and magnesium solution is added in continuation under agitation, is used in combination the salpeter solution to adjust pH=5.1, wherein described
(NH4)2HPO4The volume ratio of solution and calcium and magnesium solution is 100:167；Then by above-mentioned, the hydro-thermal reaction container containing reaction solution is placed in
In reaction kettle, 180 DEG C are gradually heating in Muffle furnace, it is Temperature fall at 180 DEG C after reaction 3-10h to keep temperature；
(3) the mixture centrifugation after reaction in step (2) is removed into supernatant, solids centrifuges in removal again wash with distilled water
Clear liquid recycles 4-8 times, until supernatant PH>7, by the remaining solid object after removal supernatant in the air environment no more than 60 DEG C
Lower drying；Then it is placed in crucible and is placed in tube furnace, be gradually heating to 500-700 DEG C, calcine natural cooling after 5-10h,
Solid powder is obtained, i.e., spherical porous nanometer hydroxyapatite.
2. a kind of preparation method of spherical porous nanometer hydroxyapatite as described in claim 1, which is characterized in that described
(NH4)2HPO4A concentration of 0.1mol/L of solution.
3. a kind of preparation method of spherical porous nanometer hydroxyapatite as described in claim 1, which is characterized in that the template
Agent is aqueous solution one or more kinds of in gelatin, xanthans, sodium alginate or Glucomannan.
4. a kind of preparation method of nanometer hydroxyapatite spherical porous as described in claim 1 or 3, which is characterized in that described
Template is the aqueous gelatin solution of 0.12%wt, and institute's gelatin water solution and the (NH4)2HPO4The volume ratio of solution is 23:
20。
5. a kind of preparation method of spherical porous nanometer hydroxyapatite as described in claim 1, which is characterized in that the calcium and magnesium
In solution, the Ca (NO3)2.4H2A concentration of 0.02361g/mL of O solution, the MgCl2.6H2O solution it is a concentration of
0.01794g/ml。
6. a kind of preparation method of spherical porous nanometer hydroxyapatite as described in claim 1, which is characterized in that step (2)
In, the NaHCO of 0.01-0.2%wt is added before adjusting pH=5.13Solution, and the NaHCO3Solution and the (NH4)2HPO4
The volume ratio of solution is 1-2:20.
7. a kind of preparation method of spherical porous nanometer hydroxyapatite as described in claim 1, which is characterized in that step (3)
In, the calcining temperature-rise period includes following three steps：A) the heating rate of 5 DEG C/min controls the solids not high
2h is handled in 200 DEG C of air environment；B) the heating rate of 5 DEG C/min controls argon gas of the solids at 500-560 DEG C
3-8h is handled in environment；C) cooled to room temperature.
8. a kind of preparation method of spherical porous nanometer hydroxyapatite as described in claim 1, which is characterized in that step (3)
In, the calcining temperature-rise period includes following three steps：A) the heating rate of 5 DEG C/min controls the solids not high
2h is handled in 200 DEG C of air environment；B) the heating rate of 5 DEG C/min controls argon gas of the solids at 560-600 DEG C
3-8h is handled in environment；C) cooled to room temperature.
9. a kind of preparation method of spherical porous nanometer hydroxyapatite as described in claim 1, which is characterized in that step (3)
In, the calcining temperature-rise period includes following three steps：A) the heating rate of 5 DEG C/min controls the solids not high
2h is handled in 200 DEG C of air environment；B) the heating rate of 5 DEG C/min controls argon gas of the solids at 600-700 DEG C
3-8h is handled in environment；C) cooled to room temperature.
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