CN104071763A - Preparation method of multi-ion bone-like apatite and multi-ion bone-like apatite - Google Patents
Preparation method of multi-ion bone-like apatite and multi-ion bone-like apatite Download PDFInfo
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Abstract
The invention belongs to the field of biomaterials, and especially relates to a preparation method of multi-ion bone-like apatite, and multi-ion bone-like apatite prepared by the preparation method. The apatite is prepared according to the chemical components and ratios of inorganic phase of natural bones, and soluble inorganic salts are taken as the raw material to in-vitro prepare multi-ion doped multi-ion bone-like apatite with a regular or irregular morphology through a self-assembling method or a chemical precipitation method. The apatite has a similar chemical composition as the inorganic phase of natural bones, has similar physical, chemical and biological properties, and can be used to supplement or repair bone tissues, such as dental filling and repairing, bone filling and repairing, and the like.
Description
Technical field
The invention belongs to technical field of biological material, the particularly preparation method of polyion type osteoid apatite, and the polyion type osteoid apatite being obtained by this preparation method.
Background technology
In natural bone, the inorganic phase composition of mineralising is osteoid apatite.Osteoid apatite is that hydroxyapatite (HA) is through Na
+, K
+, Mg
2+, Cl
-, F
-the mixture forming after heterozygosis Deng mineral ion.The molecular formula of HA is Ca
10(PO
4)
6(OH)
2, many ionic radius and Ca
2+, PO
4 3-, OH
-close positively charged ion and negatively charged ion can both enter the nucleating growth of the lattice participation crystal of HA.HA after heterozygosis has just become osteoid apatite, and crystalline structure has also become hexagonal system from original folk prescription crystallographic system.In natural bone, osteoid apatite is the storage vault of mineral ion in organism, is keeping chemical equilibrium with biological fluid.Various mineral ions play a very important role for the normal activities that maintains organism, such as: 1) Na
+, maintain acid base equilibrium in body, contribute to nerve, muscle, the normal operation of blood pressure, the Na in bone
+accounted for 1/3 of whole organism.The people (U.S.) such as Edelman IS find by radioisotope method, within 24 hours, and about 40% Na in bone
+can participate in the middle of metabolic processes.2) K
+, maintain membrane permeability and press, keep muscle irritability, in bone mineralising and Biochemical processes, there is activity.3) Mg
2+, be mainly distributed in cell, can activate the activity of plurality of enzymes in organism.Mg
2+60%～65% is present in bone and tooth, and 27% is present in soft tissue.The people (U.S.) such as Neumann WF find the Mg existing in bone
2+ion has 90% surface at phosphorite crystal.4) Cl
-be maximum negatively charged ion in organism, participate in transmembrane transport, for bone resorption process provides sour environment, activate the activity of osteoclast.5) F
-, a small amount of fluorion can be stablized the crystalline structure of phosphatic rock, prevents the formation of decayed tooth.The people (Portugal) such as Kannan S have studied the HA that has prepared the single hydridization of above-mentioned mineral ion or be total to hydridization, and product is better than the not HA of hydridization on a certain physical and chemical performance.In natural bone, osteoid apatite, in the process of nucleating growth, except being subject to the hybridization affect of mineral ion, is also subject to induction nucleation and the regular growth of some protein molecules in the interior osseous tissue of body.These protein molecules are mainly collagen and noncollagen protein matter, contain numerous polypeptide keys on molecular chain, carboxyl key, organophosphorus, the chemical groups such as sulfydryl, can with body fluid in Ca
2+, Mg
2+, P ion plasma is by the mutual key of electrostatic attraction weak interaction force and be assembled into osteoid apatite.The chemical constitution of osteoid apatite and composition ratio in simulating nature bone of the present invention, utilize self-assembly method or chemical precipitation method to prepare the polyion type osteoid apatite of rule and erose ion doping in vitro.
Summary of the invention
One of object of the present invention is to provide a kind of self-assembly method or chemical precipitation method utilized, in the external method of preparing rule and erose polyion type osteoid apatite, the polyion type osteoid apatite of preparing has the chemical constitution identical with natural bone inorganic phase, similar physical and chemical performance and biology performance, can be directly used in the reparation of body bone tissue.
Two of object of the present invention is to provide a kind of polyion type osteoid apatite being obtained by the preparation method of object one.
The preparation method of polyion type osteoid apatite of the present invention comprises the following steps:
(1) preparation cationic solution: under temperature is 0 ℃～37 ℃ and well-beaten condition, sodium salt as positively charged ion inorganic salt, sylvite, magnesium salts, mantoquita, zinc salt, molysite, calcium salt and strontium salt are dissolved in and in deionized water, obtain mixed solution, wherein, the Na in mixed solution
+concentration be 0.001～1mol/l, K
+concentration be 0.001～0.01mol/l, Mg
2+concentration be 0.001～0.002mol/l, Cu
2+concentration be 0.0001～0.0004mol/l, Zn
2+concentration be 0.001～0.006mol/l, Fe
3+concentration be 0.001～0.0015mol/l, Ca
2+concentration be 0.0025～2mol/l, Sr
2+concentration be 0.001～0.6mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain cationic solution;
(2) preparation anion solutions: under temperature is 0 ℃～37 ℃ and well-beaten condition, the villaumite as anionic inorganic salt, villiaumite, carbonate, silicate, vitriol and microcosmic salt are dissolved in deionization and obtain mixed solution, wherein, the Cl in mixed solution
-concentration be 0.001～0.2mol/l, F
-concentration be 0.001～0.01mol/l, CO
3 2-concentration be 0.001～0.027mol/l, SiO
3 2-concentration be 0.0001～0.00015mol/l, SO
4 2-concentration be 0.0001～0.0005mol/l, PO
4 3-concentration be 0.002～1.2mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain anion solutions;
(3) according to the volume ratio of anion solutions and cationic solution, be 0.1～90, the cationic solution that step (1) is obtained is added drop-wise in the anion solutions that step (2) obtains and obtains mixed solution according to the flow velocity of 0.1ml/h～5l/h, or the anion solutions that step (2) is obtained is added drop-wise in the cationic solution that step (1) obtains and obtains mixed solution according to the flow velocity of 0.1ml/h～5l/h; Stirring fully mixes them, in the process stirring, with ammoniacal liquor, sodium hydroxide, potassium hydroxide, calcium hydroxide, HCl-Tris damping fluid, phosphate buffered saline buffer or Dulbecco phosphate buffered saline buffer (DPBS), regulates the pH of mixed solution between 6.5～13.5;
(4) pH step (3) being obtained is adjusted between 0 ℃～90 ℃ in the temperature of reaction of the mixed solution between 6.5～13.5, and under the condition of standing or lasting stirring (speed that preferably continues to stir is 50rpm～3000rpm), sustained reaction is 1 hour～7 days; When step (3) is the pH between 6.5～13.5 time that regulates mixed solution with ammoniacal liquor, sodium hydroxide, potassium hydroxide or calcium hydroxide in the process stirring, in the process of standing or lasting stirring, constantly with ammoniacal liquor, sodium hydroxide, potassium hydroxide, calcium hydroxide, HCl-Tris damping fluid, phosphate buffered saline buffer or Dulbecco phosphate buffered saline buffer, regulate the pH of mixed solution between 6.5～13.5; When step (3) is the pH between 6.5～13.5 time that regulates mixed solution with HCl-Tris damping fluid, phosphate buffered saline buffer or Dulbecco phosphate buffered saline buffer in the process stirring, in the process of standing or lasting stirring without regulating again pH; After reaction finishes, obtain white emulsion;
(5) white emulsion step (4) being obtained is separated into solid-liquid two-phase (can white emulsion be separated into solid-liquid two-phase by decompress filter method or centrifugal), the deionized water wash for white solid obtaining (preferably the number of times of washing is 1～5); Then by the white solid obtaining dry (can adopt freeze-drying, high-temperature oven drying method or spray-drying process), obtain polyion type osteoid apatite.
The size of polyion type osteoid apatite prepared by the present invention is 10nm～150 μ m; Be shaped as spherical, semisphere, flowers shape, needle-like, bar-shaped or irregularly shaped.
Described is dissolved in the sodium salt as positively charged ion inorganic salt, sylvite, magnesium salts, mantoquita, zinc salt, molysite, calcium salt and strontium salt in deionized water, preferably according to the order of sodium salt, sylvite, magnesium salts, mantoquita, zinc salt, molysite, calcium salt and strontium salt, is dissolved in deionized water.
Described is dissolved in the villaumite as anionic inorganic salt, villiaumite, carbonate, silicate, vitriol and microcosmic salt in deionization, preferably according to the order of villaumite, villiaumite, carbonate, silicate, vitriol and microcosmic salt, is dissolved in deionization.
Described sodium salt is selected from a kind of in sodium-chlor, SODIUMNITRATE, sodium carbonate, sodium bicarbonate.
Described sylvite is Repone K or saltpetre.
Described magnesium salts is magnesium chloride or magnesium nitrate.
Described mantoquita is selected from a kind of in cupric chloride, copper sulfate, cupric nitrate.
Described zinc salt is zinc nitrate or zinc chloride.
Described molysite is iron nitrate or iron(ic) chloride.
Described calcium salt is selected from a kind of in nitrocalcite, calcium chloride, calcium hydroxide, secondary calcium phosphate, monocalcium phosphate, dicalcium phosphate, lime acetate, calcium carbonate.
Described strontium salt is strontium nitrate or strontium chloride.
Described villaumite is sodium-chlor or Repone K.
Described villiaumite is Sodium Fluoride.
Described carbonate is selected from a kind of in sodium carbonate, sodium bicarbonate, salt of wormwood, saleratus.
Described silicate is water glass.
Described vitriol is sodium sulfate or potassium sulfate.
Described microcosmic salt is selected from a kind of in Secondary ammonium phosphate, dipotassium hydrogen phosphate, Sodium phosphate dibasic, primary ammonium phosphate, potassium primary phosphate, SODIUM PHOSPHATE, MONOBASIC.
The present invention is according to the Chemical Composition of natural bone inorganic phase and ratio, take soluble inorganic salt as raw material, the polyion type bone-like apatite stone material of the rule that employing self-assembly method (standing) or chemical precipitation method (stirring) are manually prepared in vitro or the doping of the polyion of irregular pattern, there is the chemical constitution identical with natural bone inorganic phase, similar physical and chemical performance and biology performance, can be for the filling reparation (as tooth filling and reparation, bone filling and reparation etc.) of osseous tissue.
Accompanying drawing explanation
Fig. 1. the electron micrograph of the spherical polyion type osteoid apatite of the embodiment of the present invention 1.
Fig. 2. the electron micrograph of the hemispherical polyion type osteoid apatite of the embodiment of the present invention 2.
Fig. 3. the electron micrograph of the flowers shape polyion type osteoid apatite of the embodiment of the present invention 3.
Fig. 4. the electron micrograph of the needle-like polyion type osteoid apatite of the embodiment of the present invention 4.
Fig. 5. the electron micrograph of the bar-shaped polyion type osteoid apatite of the embodiment of the present invention 5.
Fig. 6. the electron micrograph of the irregular polyion type osteoid apatite of the embodiment of the present invention 6.
Embodiment
Embodiment 1
(1) preparation cationic solution: under temperature is 0 ℃ and well-beaten condition, sodium-chlor as positively charged ion inorganic salt, Repone K, magnesium chloride, cupric chloride, zinc chloride, iron(ic) chloride, nitrocalcite and strontium nitrate are dissolved in 100ml deionized water and obtain mixed solution according to said sequence, wherein, the Na in mixed solution
+concentration be 1.0mol/l, K
+concentration be 0.01mol/l, Mg
2+concentration be 0.002mol/l, Cu
2+concentration be 0.0004mol/l, Zn
2+concentration be 0.006mol/l, Fe
3+concentration be 0.0015mol/l, Ca
2+concentration be 0.0025mol/l, Sr
2+concentration be 0.001mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain cationic solution;
(2) preparation anion solutions: under temperature is 0 ℃ and well-beaten condition, sodium-chlor as anionic inorganic salt, Sodium Fluoride, sodium bicarbonate, water glass, potassium sulfate and Secondary ammonium phosphate are dissolved in 10ml deionized water and obtain mixed solution according to said sequence, wherein, the Cl in mixed solution
-concentration be 0.001mol/l, F
-concentration be 0.01mol/l, CO
3 2-concentration be 0.027mol/l, SiO
3 2-concentration be 0.00015mol/l, SO
4 2-concentration be 0.0005mol/l, PO
4 3-concentration be 0.002mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain anion solutions;
(3) according to the volume ratio of anion solutions and cationic solution, be 0.1, the cationic solution that step (1) is obtained is added drop-wise in the anion solutions that step (2) obtains and obtains mixed solution according to the flow velocity of 0.1ml/h, or the anion solutions that step (2) is obtained is added drop-wise in the cationic solution that step (1) obtains and obtains mixed solution according to the flow velocity of 0.1ml/h; Stirring fully mixes them, and in the process stirring, with HCl-Tris damping fluid, regulating the pH of mixed solution is 7.4;
(4) temperature of reaction of the mixed solution that pH step (3) being obtained is 7.4 is adjusted to 90 ℃, and under standing condition, sustained reaction is 7 days; After reaction finishes, obtain white emulsion;
(5) white emulsion step (4) being obtained is separated into solid-liquid two-phase by decompress filter method or centrifugal by white emulsion, the white solid obtaining deionized water wash 1 time; Then adopt freeze-drying, high-temperature oven drying method or spray-drying process to be dried the white solid obtaining, obtain size for the polyion type osteoid apatite of 400nm～700nm; Be shaped as spherical; The SEM of product as shown in Figure 1.
Embodiment 2
(1) preparation cationic solution: under temperature is 20 ℃ and well-beaten condition, sodium-chlor as positively charged ion inorganic salt, Repone K, magnesium chloride, cupric chloride, zinc chloride, iron(ic) chloride, calcium chloride and strontium nitrate are dissolved in 200ml deionized water and obtain mixed solution according to said sequence, wherein, the Na in mixed solution
+concentration be 1.0mol/l, K
+concentration be 0.01mol/l, Mg
2+concentration be 0.001mol/l, Cu
2+concentration be 0.0001mol/l, Zn
2+concentration be 0.001mol/l, Fe
3+concentration be 0.001mol/l, Ca
2+concentration be 0.0025mol/l, Sr
2+concentration be 0.6mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain cationic solution;
(2) preparation anion solutions: under temperature is 20 ℃ and well-beaten condition, sodium-chlor as anionic inorganic salt, Sodium Fluoride, sodium bicarbonate, water glass, potassium sulfate and Sodium phosphate dibasic are dissolved in 100ml deionized water and obtain mixed solution according to said sequence, wherein, the Cl in mixed solution
-concentration be 0.01mol/l, F
-concentration be 0.001mol/l, CO
3 2-concentration be 0.001mol/l, SiO
3 2-concentration be 0.0001mol/l, SO
4 2-concentration be 0.0001mol/l, PO
4 3-concentration be 0.002mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain anion solutions;
(3) according to the volume ratio of anion solutions and cationic solution, be 0.5, the cationic solution that step (1) is obtained is added drop-wise in the anion solutions that step (2) obtains and obtains mixed solution according to the flow velocity of 5l/h, or the anion solutions that step (2) is obtained is added drop-wise in the cationic solution that step (1) obtains and obtains mixed solution according to the flow velocity of 5l/h; Stirring fully mixes them, and in the process stirring, with Dulbecco phosphate buffered saline buffer (DPBS), regulating the pH of mixed solution is 7.0;
(4) temperature of reaction of the mixed solution that pH step (3) being obtained is 7.0 is adjusted to 60 ℃, and under standing condition, sustained reaction is 3 days; After reaction finishes, obtain white emulsion;
(5) white emulsion step (4) being obtained is separated into solid-liquid two-phase by decompress filter method or centrifugal by white emulsion, the white solid obtaining deionized water wash 5 times; Then adopt freeze-drying, high-temperature oven drying method or spray-drying process to be dried the white solid obtaining, obtaining size is the polyion type osteoid apatite of 10 μ m～100 μ m; Be shaped as semisphere; The SEM of product as shown in Figure 2.
Embodiment 3
(1) preparation cationic solution: under temperature is 10 ℃ and well-beaten condition, sodium-chlor as positively charged ion inorganic salt, Repone K, magnesium chloride, cupric chloride, zinc chloride, iron(ic) chloride, calcium chloride and strontium nitrate are dissolved in 100ml deionized water and obtain mixed solution according to said sequence, wherein, the Na in mixed solution
+concentration be 0.1mol/l, K
+concentration be 0.005mol/l, Mg
2+concentration be 0.0015mol/l, Cu
2+concentration be 0.0003mol/l, Zn
2+concentration be 0.002mol/l, Fe
3+concentration be 0.0012mol/l, Ca
2+concentration be 0.1mol/l, Sr
2+concentration be 0.001mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain cationic solution;
(2) preparation anion solutions: under temperature is 10 ℃ and well-beaten condition, Repone K as anionic inorganic salt, Sodium Fluoride, sodium bicarbonate, water glass, sodium sulfate and dipotassium hydrogen phosphate are dissolved in 9000ml deionized water and obtain mixed solution according to said sequence, wherein, the Cl in mixed solution
-concentration be 0.005mol/l, F
-concentration be 0.005mol/l, CO
3 2-concentration be 0.0015mol/l, SiO
3 2-concentration be 0.0003mol/l, SO
4 2-concentration be 0.0002mol/l, PO
4 3-concentration be 0.5mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain anion solutions;
(3) according to the volume ratio of anion solutions and cationic solution, be 90, the cationic solution that step (1) is obtained is added drop-wise in the anion solutions that step (2) obtains and obtains mixed solution according to the flow velocity of 200ml/h, or the anion solutions that step (2) is obtained is added drop-wise in the cationic solution that step (1) obtains and obtains mixed solution according to the flow velocity of 200ml/h; Stirring fully mixes them, and in the process stirring, with phosphate buffered saline buffer, regulating the pH of mixed solution is 6.5;
(4) temperature of reaction of the mixed solution that pH step (3) being obtained is 6.5 is adjusted to 80 ℃, and under standing condition, sustained reaction is 2 days; After reaction finishes, obtain white emulsion;
(5) white emulsion step (4) being obtained is separated into solid-liquid two-phase by decompress filter method or centrifugal by white emulsion, the white solid obtaining deionized water wash 2 times; Then adopt freeze-drying, high-temperature oven drying method or spray-drying process to be dried the white solid obtaining, obtaining size is the polyion type osteoid apatite of 10 μ m～150 μ m; Be shaped as flowers shape; The SEM of product as shown in Figure 3.
Embodiment 4
(1) preparation cationic solution: under temperature is 37 ℃ and well-beaten condition, sodium-chlor as positively charged ion inorganic salt, Repone K, magnesium chloride, cupric chloride, zinc chloride, iron(ic) chloride, calcium chloride and strontium nitrate are dissolved in 400ml deionized water and obtain mixed solution, wherein, the Na in mixed solution
+concentration be 1.0mol/l, K
+concentration be 0.01mol/l, Mg
2+concentration be 0.002mol/l, Cu
2+concentration be 0.0001mol/l, Zn
2+concentration be 0.002mol/l, Fe
3+concentration be 0.001mol/l, Ca
2+concentration be 0.60mol/l, Sr
2+concentration be 0.3mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain cationic solution;
(2) preparation anion solutions: under temperature is 37 ℃ and well-beaten condition, Repone K as anionic inorganic salt, Sodium Fluoride, sodium bicarbonate, water glass, sodium sulfate and dipotassium hydrogen phosphate are dissolved in 250ml deionized water and obtain mixed solution, wherein, the Cl in mixed solution
-concentration be 0.10mol/l, F
-concentration be 0.006mol/l, CO
3 2-concentration be 0.027mol/l, SiO
3 2-concentration be 0.0001mol/l, SO
4 2-concentration be 0.0004mol/l, PO
4 3-concentration be 0.36mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain anion solutions;
(3) according to the volume ratio of anion solutions and cationic solution, be 0.625, the cationic solution that step (1) is obtained is added drop-wise in the anion solutions that step (2) obtains and obtains mixed solution according to the flow velocity of 500ml/h, or the anion solutions that step (2) is obtained is added drop-wise in the cationic solution that step (1) obtains and obtains mixed solution according to the flow velocity of 500ml/h; Stirring fully mixes them, and in the process stirring, with ammoniacal liquor, regulating the pH of mixed solution is 9.0;
(4) temperature of reaction of the mixed solution that pH step (3) being obtained is 9.0 is adjusted to 25 ℃, continues stirring reaction 1 hour in stir speed (S.S.) under the condition that is 3000rpm; In the process stirring, constantly with ammoniacal liquor, regulate the pH of mixed solution, making pH is 9.0; After reaction finishes, obtain white emulsion;
(5) white emulsion step (4) being obtained is separated into solid-liquid two-phase by decompress filter method or centrifugal by white emulsion, the white solid obtaining deionized water wash 4 times; Then adopt freeze-drying, high-temperature oven drying method or spray-drying process to be dried the white solid obtaining, obtain size for the polyion type osteoid apatite of 10nm～700nm; Be shaped as needle-like; The SEM of product as shown in Figure 4.
Embodiment 5
(1) preparation cationic solution: under temperature is 25 ℃ and well-beaten condition, sodium-chlor as positively charged ion inorganic salt, Repone K, magnesium chloride, cupric chloride, zinc chloride, iron(ic) chloride, nitrocalcite and strontium nitrate are dissolved in 500ml deionized water and obtain mixed solution according to said sequence, wherein, the Na in mixed solution
+concentration be 0.2mol/l, K
+concentration be 0.007mol/l, Mg
2+concentration be 0.002mol/l, Cu
2+concentration be 0.0002mol/l, Zn
2+concentration be 0.006mol/l, Fe
3+concentration be 0.001mol/l, Ca
2+concentration be 0.60mol/l, Sr
2+concentration be 0.2mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain cationic solution;
(2) preparation anion solutions: under temperature is 10 ℃ and well-beaten condition, sodium-chlor as anionic inorganic salt, Sodium Fluoride, sodium bicarbonate, water glass, sodium sulfate and Sodium phosphate dibasic are dissolved in 400ml deionized water and obtain mixed solution according to said sequence, wherein, the Cl in mixed solution
-concentration be 0.1mol/l, F
-concentration be 0.01mol/l, CO
3 2-concentration be 0.01mol/l, SiO
3 2-concentration be 0.0001mol/l, SO
4 2-concentration be 0.0002mol/l, PO
4 3-concentration be 0.36mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain anion solutions;
(3) according to the volume ratio of anion solutions and cationic solution, be 0.8, the cationic solution that step (1) is obtained is added drop-wise in the anion solutions that step (2) obtains and obtains mixed solution according to the flow velocity of 1l/h, or the anion solutions that step (2) is obtained is added drop-wise in the cationic solution that step (1) obtains and obtains mixed solution according to the flow velocity of 1l/h; Stirring fully mixes them, and in the process stirring, with sodium hydroxide, regulating the pH of mixed solution is 13.5;
(4) temperature of reaction of the mixed solution that pH step (3) being obtained is 13.5 is adjusted to 80 ℃, continues stirring reaction 24 hours in stir speed (S.S.) under the condition that is 50rpm; In the process stirring, constantly with sodium hydroxide, regulate the pH of mixed solution, making pH is 13.5; After reaction finishes, obtain white emulsion;
(5) white emulsion step (4) being obtained is separated into solid-liquid two-phase by decompress filter method or centrifugal by white emulsion, the white solid obtaining deionized water wash 3 times; Then adopt freeze-drying, high-temperature oven drying method or spray-drying process to be dried the white solid obtaining, obtain size for the polyion type osteoid apatite of 600nm～10 μ m; Be shaped as bar-shaped; The SEM of product as shown in Figure 5.
Embodiment 6
(1) preparation cationic solution: under temperature is 20 ℃ and well-beaten condition, sodium-chlor as positively charged ion inorganic salt, Repone K, magnesium chloride, cupric chloride, zinc chloride, iron(ic) chloride, nitrocalcite and strontium nitrate are dissolved in 1000ml deionized water and obtain mixed solution according to said sequence, wherein, the Na in mixed solution
+concentration be 1.0mol/l, K
+concentration be 0.01mol/l, Mg
2+concentration be 0.002mol/l, Cu
2+concentration be 0.0001mol/l, Zn
2+concentration be 0.002mol/l, Fe
3+concentration be 0.001mol/l, Ca
2+concentration be 2.0mol/l, Sr
2+concentration be 0.001mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain cationic solution;
(2) preparation anion solutions: under temperature is 20 ℃ and well-beaten condition, Repone K as anionic inorganic salt, Sodium Fluoride, sodium bicarbonate, water glass, sodium sulfate and Secondary ammonium phosphate are dissolved in 500ml deionized water and obtain mixed solution according to said sequence, wherein, the Cl in mixed solution
-concentration be 0.2mol/l, F
-concentration be 0.001mol/l, CO
3 2-concentration be 0.027mol/l, SiO
3 2-concentration be 0.00015mol/l, SO
4 2-concentration be 0.0004mol/l, PO
4 3-concentration be 1.20mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain anion solutions;
(3) according to the volume ratio of anion solutions and cationic solution, be 0.2, the cationic solution that step (1) is obtained is added drop-wise in the anion solutions that step (2) obtains and obtains mixed solution according to the flow velocity of 200ml/h, or the anion solutions that step (2) is obtained is added drop-wise in the cationic solution that step (1) obtains and obtains mixed solution according to the flow velocity of 200ml/h; Stirring fully mixes them, and in the process stirring, with potassium hydroxide, regulating the pH of mixed solution is 10.0;
(4) temperature of reaction of the mixed solution that pH step (3) being obtained is 10.0 is adjusted to 60 ℃, continues stirring reaction 18 hours in stir speed (S.S.) under the condition that is 600rpm; In the process stirring, constantly with potassium hydroxide, regulate the pH of mixed solution, making pH is 10.0; After reaction finishes, obtain white emulsion;
(5) white emulsion step (4) being obtained is separated into solid-liquid two-phase by decompress filter method or centrifugal by white emulsion, the white solid obtaining deionized water wash 3 times; Then adopt freeze-drying, high-temperature oven drying method or spray-drying process to be dried the white solid obtaining, obtain being shaped as erose polyion type osteoid apatite; The SEM of product as shown in Figure 6; The result of product ultimate analysis is as shown in table 1.
Table 1
。
Claims (10)
1. a preparation method for polyion type osteoid apatite, is characterized in that, described preparation method comprises the following steps:
(1) preparation cationic solution: under temperature is 0 ℃～37 ℃ and well-beaten condition, sodium salt as positively charged ion inorganic salt, sylvite, magnesium salts, mantoquita, zinc salt, molysite, calcium salt and strontium salt are dissolved in and in deionized water, obtain mixed solution, wherein, the Na in mixed solution
+concentration be 0.001～1mol/l, K
+concentration be 0.001～0.01mol/l, Mg
2+concentration be 0.001～0.002mol/l, Cu
2+concentration be 0.0001～0.0004mol/l, Zn
2+concentration be 0.001～0.006mol/l, Fe
3+concentration be 0.001～0.0015mol/l, Ca
2+concentration be 0.0025～2mol/l, Sr
2+concentration be 0.001～0.6mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain cationic solution;
(2) preparation anion solutions: under temperature is 0 ℃～37 ℃ and well-beaten condition, the villaumite as anionic inorganic salt, villiaumite, carbonate, silicate, vitriol and microcosmic salt are dissolved in deionization and obtain mixed solution, wherein, the Cl in mixed solution
-concentration be 0.001～0.2mol/l, F
-concentration be 0.001～0.01mol/l, CO
3 2-concentration be 0.001～0.027mol/l, SiO
3 2-concentration be 0.0001～0.00015mol/l, SO
4 2-concentration be 0.0001～0.0005mol/l, PO
4 3-concentration be 0.002～1.2mol/l; Filter paper or filter-cloth filtering by the mixed solution obtaining through 0< aperture≤0.45 μ m, obtain anion solutions;
(3) according to the volume ratio of anion solutions and cationic solution, be 0.1～90, the cationic solution that step (1) is obtained is added drop-wise in the anion solutions that step (2) obtains and obtains mixed solution according to the flow velocity of 0.1ml/h～5l/h, or the anion solutions that step (2) is obtained is added drop-wise in the cationic solution that step (1) obtains and obtains mixed solution according to the flow velocity of 0.1ml/h～5l/h; Stirring fully mixes them, in the process stirring, with ammoniacal liquor, sodium hydroxide, potassium hydroxide, calcium hydroxide, HCl-Tris damping fluid, phosphate buffered saline buffer or Dulbecco phosphate buffered saline buffer, regulates the pH of mixed solution between 6.5～13.5;
(4) pH step (3) being obtained is adjusted between 0 ℃～90 ℃ in the temperature of reaction of the mixed solution between 6.5～13.5, and under the condition of standing or lasting stirring, sustained reaction is 1 hour～7 days; When step (3) is the pH between 6.5～13.5 time that regulates mixed solution with ammoniacal liquor, sodium hydroxide, potassium hydroxide or calcium hydroxide in the process stirring, in the process of standing or lasting stirring, constantly with ammoniacal liquor, sodium hydroxide, potassium hydroxide, calcium hydroxide, HCl-Tris damping fluid, phosphate buffered saline buffer or Dulbecco phosphate buffered saline buffer, regulate the pH of mixed solution between 6.5～13.5; When step (3) is the pH between 6.5～13.5 time that regulates mixed solution with HCl-Tris damping fluid, phosphate buffered saline buffer or Dulbecco phosphate buffered saline buffer in the process stirring, in the process of standing or lasting stirring without regulating again pH; After reaction finishes, obtain white emulsion;
(5) white emulsion step (4) being obtained is separated into solid-liquid two-phase, the white solid deionized water wash obtaining; Then the white solid obtaining is dry, obtain polyion type osteoid apatite.
2. preparation method according to claim 1, it is characterized in that: described is dissolved in the sodium salt as positively charged ion inorganic salt, sylvite, magnesium salts, mantoquita, zinc salt, molysite, calcium salt and strontium salt in deionized water, is to be dissolved in deionized water according to the order of sodium salt, sylvite, magnesium salts, mantoquita, zinc salt, molysite, calcium salt and strontium salt;
Described is dissolved in the villaumite as anionic inorganic salt, villiaumite, carbonate, silicate, vitriol and microcosmic salt in deionization, is to be dissolved in deionization according to the order of villaumite, villiaumite, carbonate, silicate, vitriol and microcosmic salt.
3. preparation method according to claim 1 and 2, is characterized in that: described sodium salt is selected from a kind of in sodium-chlor, SODIUMNITRATE, sodium carbonate, sodium bicarbonate; Described sylvite is Repone K or saltpetre; Described magnesium salts is magnesium chloride or magnesium nitrate; Described mantoquita is selected from a kind of in cupric chloride, copper sulfate, cupric nitrate; Described zinc salt is zinc nitrate or zinc chloride; Described molysite is iron nitrate or iron(ic) chloride; Described calcium salt is selected from a kind of in nitrocalcite, calcium chloride, calcium hydroxide, secondary calcium phosphate, monocalcium phosphate, dicalcium phosphate, lime acetate, calcium carbonate; Described strontium salt is strontium nitrate or strontium chloride.
4. preparation method according to claim 1 and 2, is characterized in that: described villaumite is sodium-chlor or Repone K; Described villiaumite is Sodium Fluoride; Described carbonate is selected from a kind of in sodium carbonate, sodium bicarbonate, salt of wormwood, saleratus; Described silicate is water glass; Described vitriol is sodium sulfate or potassium sulfate; Described microcosmic salt is selected from a kind of in Secondary ammonium phosphate, dipotassium hydrogen phosphate, Sodium phosphate dibasic, primary ammonium phosphate, potassium primary phosphate, SODIUM PHOSPHATE, MONOBASIC.
5. preparation method according to claim 1, is characterized in that: the speed of described lasting stirring is 50rpm～3000rpm.
6. preparation method according to claim 1, is characterized in that: it is to adopt decompress filter method or centrifugal that the described white emulsion that step (4) is obtained is separated into solid-liquid two-phase.
7. preparation method according to claim 1, is characterized in that: described dry be to adopt freeze-drying, high-temperature oven drying method or spray-drying process.
8. preparation method according to claim 1, is characterized in that: being shaped as of described polyion type osteoid apatite is spherical, semisphere, flowers shape, needle-like, bar-shaped or irregularly shaped, and size is 10nm～150 μ m.
9. a polyion type osteoid apatite, is characterized in that: according to the preparation method described in claim 1～8 any one, prepare.
10. polyion type osteoid apatite according to claim 9, it is characterized in that: described polyion type osteoid apatite has the chemical constitution identical with natural bone inorganic phase, similar physical and chemical performance and biology performance, for the filling reparation of body bone tissue.
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| CN110791653A (en) * | 2019-11-11 | 2020-02-14 | 浙江工商大学 | Method for extracting copper by using hydroxyapatite-containing waste |
| CN114159622A (en) * | 2021-12-03 | 2022-03-11 | 清华大学 | Mineralized collagen nano-particles doped with active elements and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108478876A (en) * | 2018-04-27 | 2018-09-04 | 南充市中心医院 | A kind of vascularization promoting bone tissue engineering scaffold and its preparation method and application |
| CN108478876B (en) * | 2018-04-27 | 2020-12-18 | 南充市中心医院 | Vascularization promoting bone tissue engineering scaffold and preparation method and application thereof |
| CN109432487A (en) * | 2018-12-29 | 2019-03-08 | 广州贝奥吉因生物科技有限公司 | A kind of bone wax and its preparation method and application with Bone Defect Repari function |
| CN109432487B (en) * | 2018-12-29 | 2021-08-13 | 广州贝奥吉因生物科技有限公司 | Bone wax with bone repair function and preparation method and application thereof |
| CN110791653A (en) * | 2019-11-11 | 2020-02-14 | 浙江工商大学 | Method for extracting copper by using hydroxyapatite-containing waste |
| CN114159622A (en) * | 2021-12-03 | 2022-03-11 | 清华大学 | Mineralized collagen nano-particles doped with active elements and preparation method thereof |
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