CN106115644A - A kind of preparation method of hydroxyapatite structure - Google Patents
A kind of preparation method of hydroxyapatite structure Download PDFInfo
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- CN106115644A CN106115644A CN201610488351.0A CN201610488351A CN106115644A CN 106115644 A CN106115644 A CN 106115644A CN 201610488351 A CN201610488351 A CN 201610488351A CN 106115644 A CN106115644 A CN 106115644A
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- hydroxyapatite structure
- hydroxyapatite
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- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical group [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 title claims abstract description 32
- 239000000679 carrageenan Substances 0.000 claims abstract description 19
- 229920001525 carrageenan Polymers 0.000 claims abstract description 19
- 229940113118 carrageenan Drugs 0.000 claims abstract description 19
- 239000004115 Sodium Silicate Substances 0.000 claims abstract description 18
- 229910052911 sodium silicate Inorganic materials 0.000 claims abstract description 18
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 17
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 17
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 17
- NTHWMYGWWRZVTN-UHFFFAOYSA-N sodium silicate Chemical compound [Na+].[Na+].[O-][Si]([O-])=O NTHWMYGWWRZVTN-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000011575 calcium Substances 0.000 claims abstract description 16
- 235000019795 sodium metasilicate Nutrition 0.000 claims abstract description 16
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000001099 ammonium carbonate Substances 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 235000010418 carrageenan Nutrition 0.000 claims abstract description 13
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims abstract description 13
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims abstract description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims abstract description 7
- 235000012501 ammonium carbonate Nutrition 0.000 claims abstract description 7
- 239000013078 crystal Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 238000005406 washing Methods 0.000 claims abstract description 7
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 5
- 159000000007 calcium salts Chemical class 0.000 claims abstract description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 5
- 239000010452 phosphate Substances 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 7
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 claims description 6
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 6
- 229960002918 doxorubicin hydrochloride Drugs 0.000 claims description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 4
- 239000001110 calcium chloride Substances 0.000 claims description 4
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 4
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 claims description 4
- 229910001634 calcium fluoride Inorganic materials 0.000 claims description 4
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 3
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 3
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 3
- 239000003292 glue Substances 0.000 claims 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 claims 1
- 235000019794 sodium silicate Nutrition 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 6
- 238000011068 loading method Methods 0.000 abstract description 4
- 239000002245 particle Substances 0.000 abstract description 4
- 239000000463 material Substances 0.000 description 13
- 229910052586 apatite Inorganic materials 0.000 description 12
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 12
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 10
- 239000004005 microsphere Substances 0.000 description 7
- 241000446313 Lamella Species 0.000 description 5
- 238000000034 method Methods 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- -1 silicate ion Chemical class 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229910014497 Ca10(PO4)6(OH)2 Inorganic materials 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- ZQBZAOZWBKABNC-UHFFFAOYSA-N [P].[Ca] Chemical compound [P].[Ca] ZQBZAOZWBKABNC-UHFFFAOYSA-N 0.000 description 1
- 230000033558 biomineral tissue development Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001027 hydrothermal synthesis Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000593 microemulsion method Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003980 solgel method Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- 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
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/01—Particle morphology depicted by an image
- C01P2004/03—Particle morphology depicted by an image obtained by SEM
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/30—Particle morphology extending in three dimensions
- C01P2004/32—Spheres
- C01P2004/34—Spheres hollow
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/60—Particles characterised by their size
- C01P2004/64—Nanometer sized, i.e. from 1-100 nanometer
Abstract
The invention provides the preparation method of a kind of hydroxyapatite structure, comprise the following steps: (1) is 1.6～1.7 by Ca:P mol ratio, soluble calcium salt and soluble phosphate are dissolved in water, form Ca2+Being the solution of 0.01～1mol/L, adjusting PH is 4～5；(2) 0.5～the carrageenan of 5% and .5～2% hyaluronic acid is added, 30～40 DEG C of stirrings to dissolving；(3) Ca is added2+1～5% sodium metasilicate or sodium metasilicate hydrate, form solution A；(4) ammonium carbonate or ammonium hydrogen carbonate are dissolved in water, are configured to the solution B that PH is 10～12；(5) solution B is instilled in solution A with the speed of dripping of 0.01～1ml/min, stand 12～24h；(6) centrifugal, take crystal washing, alcohol is washed, is dried, is pulverized.The hydroxyapatite structure that particle diameter is 20～50nm that the present invention can prepare good biocompatibility, drug loading is bigger.
Description
[technical field]
The present invention relates to biomineralization field, particularly relate to the preparation method of a kind of hydroxyapatite structure.
[background technology]
Hydroxyapatite (Ca10(PO4)6(OH)2) it is the host inorganic constituent of vertebrate skeletal and tooth, have
Good biocompatibility, is widely used in reparation and the replacement of biological hard tissue clinically, and filling, ear such as Cranial defect are little
Bone is replaced and vertebrae replacement etc..Meanwhile, hydroxyapatite also has good chemical stability and outstanding absorption property, and
And medicine can be realized controlled release, with many medicines or albumen all Fails To Responds, therefore it is situated between in catalyst carrier, bio-separation
Matter, especially the most of great interest in fields such as slow releasing carrier of medication.
Natural hydroxyapatite is present in the sclerous tissues such as human body and the skeleton of animal, tooth with needle form, and people
The hydroxyapatite shape of work synthesis has bar-shaped, needle-like, lamellar and spherical etc..There is fragility in irregular needle-like and lamellar morphology
Height, poor mechanical property, the easy shortcomings such as inflammation that introduce in human body, and the spherical nanometer hydroxyapatite that particle diameter is 2-50nm
Microsphere, for the form such as needle-like and lamellar, has good mobility, the shape of rule, affinity good, at organism
The advantages such as interior easily absorption.But, the drug loading of hydroxyapatite micro-sphere depends on interior porosity and the hollow knot of microsphere
Structure.At present, the preparation method of hydroxyapatite micro-sphere hydro-thermal method again, nebulization, sol-gel process, template, microemulsion method etc.,
But, utilizing these methods to prepare porous hydroxyapatite microsphere and more bother, post processing is the most comparatively laborious, easily forms impurity
Residual, affects the quality of porous microsphere.
[summary of the invention]
For the problems referred to above of the prior art, the present invention provides the preparation method of a kind of hydroxyapatite structure, it is possible to
Prepare good biocompatibility, the hydroxyapatite structure that particle diameter is 20～50nm that drug loading is bigger.
The technical scheme is that
The preparation method of a kind of hydroxyapatite structure, it is characterised in that comprise the following steps:
(1) according to the ratio that Ca:P mol ratio is 1.6～1.7, soluble calcium salt and soluble phosphate are dissolved in water, join
It is set to Ca2+Concentration is the solution of 0.01～1mol/L, and regulation PH is 4～5；
(2) adding carrageenan and hyaluronic acid in the solution of step (1) gained, the addition of described carrageenan is step
(1) the 0.5～5% of solution quality, the addition of described hyaluronic acid is the 0.5～2% of step (1) solution quality, 30～
Under the conditions of 40 DEG C, stirring is to dissolving；
(3) in the solution of step (2) gained, add sodium metasilicate or sodium metasilicate hydrate, form solution A；Described partially
The addition of sodium silicate or sodium metasilicate hydrate is Ca in step (1)2+The 1～5% of molal quantity；A small amount of Si leads in the solution
Cross aspects such as changing the dissolubility of apatite, surface chemistry and material morphology and improve structure and the pattern of Apatite materials；
(4) ammonium carbonate or ammonium hydrogen carbonate are dissolved in water, are configured to the solution B that PH is 10～12；
(5) solution B is instilled in solution A with the speed of dripping of 0.01～1ml/min, stand 12～24h；
(6) mixture of step (5) gained is centrifuged, takes crystal washing, alcohol washes, is dried, pulverizes.
Preferably, one or more during above-mentioned soluble calcium salt refers to calcium fluoride, calcium chloride, calcium nitrate.
Preferably, above-mentioned soluble phosphate refers to sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate
One or more.
Preferably, above-mentioned carrageenan is lambda-carrageenan.The helical structure of lambda-carrageenan is to the structure of Apatite materials and shape
Looks have certain regulating and controlling effect.
Preferably, the molecular weight of above-mentioned hyaluronic acid is 1,000,000～2,200,000.Hyaluronic acid contains substantial amounts of hydroxyl and carboxylic
Base, has extremely strong hydrophilic, and to Ca2+There is bigger affinity, and there is good viscoelasticity, crystallization can be controlled
During raw material migrate and migration rate, structure and the pattern that can regulate Apatite materials have certain regulating and controlling effect.
Preferably, in above-mentioned steps (1), Ca:P mol ratio is 1.65～1.67, and suitable calcium-phosphorus ratio can reduce impurity
Occur.
Preferably, in above-mentioned steps (2), the addition of carrageenan is the 0.5～2% of step (1) solution quality, hyalomitome
Addition is step (1) solution quality the 0.5～1% of acid.
Preferably, the product mean diameter of above-mentioned preparation method is 20～50nm.
Preferably, the product porosity of above-mentioned preparation method is 70～85%.
Preferably, the product of above-mentioned preparation method is that every 10mg loads 12～15 μ g/ml to the load capacity of doxorubicin hydrochloride.
The present invention has a following useful technique effect:
1) present invention can prepare the porous hydroxyapatite micro-sphere structure that mean diameter is 10～20nm, and porosity is 70
～85%, good biocompatibility, drug loading are bigger；2) present invention carrageenan, hyaluronic acid, silicate ion are to hydroxy-apatite
The structure of stone, pattern, particle diameter regulate and control, and can generate the specification spherical junctions with a large amount of hole assembled by lamella
Structure, and whole process is not added with any harmful organic solvent and little molecule poisonous, use is all to biology
The composition that body is harmless, increases the probability that class skeleton HAP is formed；3) raw material of the present invention is easy to get, and technique is simple, and the production cycle is relatively
Short, preparation condition is gentle, substantially reduces the response time, improves preparation efficiency, and post processing is simple, without any residual, material
Biocompatibility good.
[accompanying drawing explanation]
Fig. 1 is the stereoscan photograph of embodiment one.
[detailed description of the invention]
Below in conjunction with specific embodiment, the present invention is described further.
Embodiment provided below also is not used to limit the scope that the present invention is contained, and described step is not to use
To limit its execution sequence.Those skilled in the art combine existing common knowledge and are the present invention conspicuously improved, also fall
Within entering the protection domain of application claims.
Embodiment one
The preparation method of a kind of hydroxyapatite structure, comprises the following steps:
(1) it is the ratio of 1.67 according to Ca:P mol ratio, calcium fluoride and disodium hydrogen phosphate is dissolved in water, is configured to Ca2+Dense
Degree is the solution of 0.5mol/L, and regulation PH is 4～5；
(2) in the solution of step (1) gained, lambda-carrageenan and molecular weight is 1,800,000～2,200,000 hyaluronic acid are added,
The addition of described carrageenan is the 2% of step (1) solution quality, and the addition of described hyaluronic acid is step (1) solution matter
The 1.5% of amount, under the conditions of 30～40 DEG C, stirring is to dissolving；
(3) in the solution of step (2) gained, add sodium metasilicate, form solution A；The addition of described sodium metasilicate is
Ca in step (1)2+The 3% of molal quantity；A small amount of Si is in the solution by changing the dissolubility of apatite, surface chemistry and material shape
The aspects such as looks improve structure and the pattern of Apatite materials；
(4) ammonium carbonate or ammonium hydrogen carbonate are dissolved in water, are configured to the solution B that PH is 10～12；
(5) solution B is instilled in solution A with the speed of dripping of 0.5ml/min, stand 12～24h；
(6) mixture of step (5) gained is centrifuged, takes crystal washing, alcohol washes, is dried, pulverizes.
What the product lamella of above-mentioned preparation method assembled has the specification spherical structure of a large amount of hole, as it is shown in figure 1,
Mean diameter is 38nm, and porosity is 75%, and the load capacity to doxorubicin hydrochloride is that every 10mg loads 13.35 μ g/ml.
Embodiment two
The preparation method of a kind of hydroxyapatite structure, comprises the following steps:
(1) it is the ratio of 1.65 according to Ca:P mol ratio, calcium chloride and dipotassium hydrogen phosphate is dissolved in water, is configured to Ca2+Dense
Degree is the solution of 0.1mol/L, and regulation PH is 4～5；
(2) in the solution of step (1) gained, lambda-carrageenan and molecular weight is 1,800,000～2,200,000 hyaluronic acid are added,
The addition of described carrageenan is the 1% of step (1) solution quality, and the addition of described hyaluronic acid is step (1) solution matter
The 1% of amount, under the conditions of 30～40 DEG C, stirring is to dissolving；
(3) in the solution of step (2) gained, add sodium metasilicate, form solution A；The addition of described sodium metasilicate is
Ca in step (1)2+The 2% of molal quantity；A small amount of Si is in the solution by changing the dissolubility of apatite, surface chemistry and material shape
The aspects such as looks improve structure and the pattern of Apatite materials；
(4) ammonium carbonate or ammonium hydrogen carbonate are dissolved in water, are configured to the solution B that PH is 10～12；
(5) solution B is instilled in solution A with the speed of dripping of 0.1ml/min, stand 12～24h；
(6) mixture of step (5) gained is centrifuged, takes crystal washing, alcohol washes, is dried, pulverizes.
What the product lamella of above-mentioned preparation method assembled has the specification spherical structure of a large amount of hole, and mean diameter is
45nm, porosity is 80%, and the load capacity to doxorubicin hydrochloride is that every 10mg loads 14.36 μ g/ml.
Embodiment three
The preparation method of a kind of hydroxyapatite structure, comprises the following steps:
(1) it is the ratio of 1.6 according to Ca:P mol ratio, calcium nitrate and sodium dihydrogen phosphate is dissolved in water, is configured to Ca2+Concentration
For the solution of 0.01mol/L, regulation PH is 4～5；
(2) in the solution of step (1) gained, lambda-carrageenan and molecular weight is 1,000,000～1,500,000 hyaluronic acid are added,
The addition of described carrageenan is the 0.5% of step (1) solution quality, and the addition of described hyaluronic acid is step (1) solution
The 0.5% of quality, under the conditions of 30～40 DEG C, stirring is to dissolving；
(3) in the solution of step (2) gained, add sodium metasilicate, form solution A；The addition of described sodium metasilicate is
Ca in step (1)2+The 1% of molal quantity；A small amount of Si is in the solution by changing the dissolubility of apatite, surface chemistry and material shape
The aspects such as looks improve structure and the pattern of Apatite materials；
(4) ammonium carbonate or ammonium hydrogen carbonate are dissolved in water, are configured to the solution B that PH is 10～12；
(5) solution B is instilled in solution A with the speed of dripping of 0.01ml/min, stand 12～24h；
(6) mixture of step (5) gained is centrifuged, takes crystal washing, alcohol washes, is dried, pulverizes.
What the product lamella of above-mentioned preparation method assembled has the specification spherical structure of a large amount of hole, and mean diameter is
50nm, porosity is 85%, and the load capacity to doxorubicin hydrochloride is that every 10mg loads 15 μ g/ml.
Embodiment four
The preparation method of a kind of hydroxyapatite structure, comprises the following steps:
(1) it is the ratio of 1.7 according to Ca:P mol ratio, calcium fluoride, calcium chloride, potassium dihydrogen phosphate is dissolved in water, is configured to
Ca2+Concentration is the solution of 1mol/L, and regulation PH is 4～5；
(2) in the solution of step (1) gained, lambda-carrageenan and molecular weight is 1,000,000～1,800,000 hyalomitome are added
Acid, the addition of described carrageenan is the 5% of step (1) solution quality, and the addition of described hyaluronic acid is step (1) solution
The 2% of quality, under the conditions of 30～40 DEG C, stirring is to dissolving；
(3) in the solution of step (2) gained, add sodium metasilicate hydrate, form solution A；Described sodium metasilicate is hydrated
The addition of thing is Ca in step (1)2+The 5% of molal quantity；A small amount of Si is in the solution by changing the dissolubility of apatite, surface
The aspects such as chemistry and material morphology improve structure and the pattern of Apatite materials；
(4) ammonium carbonate or ammonium hydrogen carbonate are dissolved in water, are configured to the solution B that PH is 10～12；
(5) solution B is instilled in solution A with the speed of dripping of 1ml/min, stand 12～24h；
(6) mixture of step (5) gained is centrifuged, takes crystal washing, alcohol washes, is dried, pulverizes.
What the product lamella of above-mentioned preparation method assembled has the specification spherical structure of a large amount of hole, and mean diameter is
20nm, porosity is 70%, and the load capacity to doxorubicin hydrochloride is that every 10mg loads 12 μ g/ml.
Claims (10)
1. the preparation method of a hydroxyapatite structure, it is characterised in that comprise the following steps:
(1) according to the ratio that Ca:P mol ratio is 1.6～1.7, soluble calcium salt and soluble phosphate are dissolved in water, are configured to
Ca2+Concentration is the solution of 0.01～1mol/L, and regulation PH is 4～5；
(2) adding carrageenan and hyaluronic acid in the solution of step (1) gained, the addition of described carrageenan is step (1)
The 0.5～5% of solution quality, the addition of described hyaluronic acid is the 0.5～2% of step (1) solution quality, at 30～40 DEG C
Under the conditions of, stirring is to dissolving；
(3) in the solution of step (2) gained, add sodium metasilicate or sodium metasilicate hydrate, form solution A；Described metasilicic acid
The addition of sodium or sodium metasilicate hydrate is Ca in step (1)2+The 1～5% of molal quantity；
(4) ammonium carbonate or ammonium hydrogen carbonate are dissolved in water, are configured to the solution B that PH is 10～12；
(5) solution B is instilled in solution A with the speed of dripping of 0.01～1ml/min, stand 12～24h；
(6) mixture of step (5) gained is centrifuged, takes crystal washing, alcohol washes, is dried, pulverizes.
The preparation method of hydroxyapatite structure the most according to claim 1, it is characterised in that described soluble calcium salt refers to
One or more in calcium fluoride, calcium chloride, calcium nitrate.
The preparation method of hydroxyapatite structure the most according to claim 1, it is characterised in that described soluble phosphate
Refer to sodium dihydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate one or more.
The preparation method of hydroxyapatite structure the most according to claim 1, it is characterised in that described carrageenan is λ-card
Draw glue.
The preparation method of hydroxyapatite structure the most according to claim 1, it is characterised in that dividing of described hyaluronic acid
Son amount is 1,000,000～2,200,000.
The preparation method of hydroxyapatite structure the most according to claim 1, it is characterised in that Ca in described step (1):
P mol ratio is 1.65～1.67.
The preparation method of hydroxyapatite structure the most according to claim 1, it is characterised in that card in described step (2)
Drawing addition is step (1) solution quality the 0.5～2% of glue, the addition of hyaluronic acid is step (1) solution quality
0.5～1%.
The preparation method of hydroxyapatite structure the most according to claim 1, it is characterised in that the product of described preparation method
Product mean diameter is 20～50nm.
The preparation method of hydroxyapatite structure the most according to claim 1, it is characterised in that the product of described preparation method
Product porosity is 70～85%.
The preparation method of hydroxyapatite structure the most according to claim 1, it is characterised in that described preparation method
Product is that every 10mg loads 12～15 μ g/ml to the load capacity of doxorubicin hydrochloride.
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| CN101891175A (en) * | 2010-07-08 | 2010-11-24 | 中国科学院上海硅酸盐研究所 | Enamel-shaped hydroxyapatite and preparation method and application thereof |
| US20110066242A1 (en) * | 2007-02-12 | 2011-03-17 | The Trustees Of Columbia University In The City Of New York | Biomimmetic nanofiber scaffold for soft tissue and soft tissue-to-bone repair, augmentation and replacement |
| CN103086339A (en) * | 2013-02-18 | 2013-05-08 | 中国人民解放军南京军区南京总医院 | Porous hydroxyapatite flower-like microspheres and preparation method thereof |
| CN103738932A (en) * | 2013-12-13 | 2014-04-23 | 苏州大学 | Nano-hydroxyapatite and preparation method thereof |
| CN104944399A (en) * | 2015-06-16 | 2015-09-30 | 西南科技大学 | Preparation method for hydroxyapatite microspheres |
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| US20110066242A1 (en) * | 2007-02-12 | 2011-03-17 | The Trustees Of Columbia University In The City Of New York | Biomimmetic nanofiber scaffold for soft tissue and soft tissue-to-bone repair, augmentation and replacement |
| CN101186286A (en) * | 2007-11-29 | 2008-05-28 | 同济大学 | Method for preparing ordered porous hydroxyapatite material |
| CN101891175A (en) * | 2010-07-08 | 2010-11-24 | 中国科学院上海硅酸盐研究所 | Enamel-shaped hydroxyapatite and preparation method and application thereof |
| CN103086339A (en) * | 2013-02-18 | 2013-05-08 | 中国人民解放军南京军区南京总医院 | Porous hydroxyapatite flower-like microspheres and preparation method thereof |
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| CN104944399A (en) * | 2015-06-16 | 2015-09-30 | 西南科技大学 | Preparation method for hydroxyapatite microspheres |
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