CN104192817A - Method for preparing mesoporous hydroxyapatite nanometer particle with high specific surface area by virtue of template method - Google Patents

Method for preparing mesoporous hydroxyapatite nanometer particle with high specific surface area by virtue of template method Download PDF

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CN104192817A
CN104192817A CN201410447297.6A CN201410447297A CN104192817A CN 104192817 A CN104192817 A CN 104192817A CN 201410447297 A CN201410447297 A CN 201410447297A CN 104192817 A CN104192817 A CN 104192817A
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surface area
specific surface
nano particle
mesoporous
high specific
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CN104192817B (en
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黄玉东
李大龙
贺金梅
吴亚东
王芳
程玮璐
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Harbin Institute of Technology
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Harbin Institute of Technology
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Abstract

The invention discloses a method for preparing a mesoporous hydroxyapatite nanometer particle with high specific surface area by virtue of a template method. The method comprises the following steps: firstly, mixing calcium pantothenate, F123 and a certain amount of sym-trimethylbenzene to prepare an emulsion and then dropwise adding a phosphate solution with a certain pH value into the emulsion, heating in a water bath, carrying out reflux reaction and filtering to obtain a precipitate and finally calcining the precipitate in a muffle furnace to remove a template to obtain the hydroxyapatite nanometer particle with a mesoporous structure. The mesoporous hydroxyapatite prepared by the method disclosed by the invention has the characteristics of high specific surface area, large drug loading amount and uniform pore size distribution and is distributed in a spherical nanometer state (the size is less than 100nm). The mesoporous hydroxyapatite serving as a drug carrier can well penetrate through blood vessels and cell walls to reach diseased cells. The entire preparation process is simple and the mesoporous hydroxyapatite can be produced in a large scale.

Description

Utilize the method for the high specific surface area and mesoporous hydroxyapatite nano particle of template synthesis
Technical field
The present invention relates to a kind of preparation method of mesoporous hydroxyapatite nano particle.
Background technology
Hydroxyapatite (Hydroxyapatite is called for short HAp), its chemical formula is Ca 10(PO 4) 6(OH) 2, be the main inorganic composition of sclerous tissues in mammalian body, very approaching with natural apatite mineral structure, belong to hexagonal system, in people's bone, account for 77%, in dentary, up to 97%, be the main inorganic composition of vertebrates bone and tooth.
Hydroxyapatite is as the chief component composition of natural bone, there is good biocompatibility and higher biological activity, because it contains the necessary calcium of tissue and phosphoric, after implanting, under the effect of body fluid, calcium, the phosphoric material surface that can dissociate, absorbed by body tissue gradually, and carry out Chemical bond with skeleton tissue, there is bone guided, induction bone cell growth, final section or all absorbed by tissue and replace, induce the formation of new bone and provide support for it, it is the biological ceramics that a class can be combined with organism bone tooth completely, it is desirable hard tissue repair, replacement material.Be widely used at present in vertebrae is replaced, bone is damaged reparation, or with the compound material of preparing biological bone such as collagen, chitosan, silk fibroin, poly(lactic acid).
The biological degradability of hydroxyapatite is as the optimal material of drug disposition nano-carrier.Hydroxyapatite is as pharmaceutical carrier, and the effect aspect medicament slow release is to make Plasma Concentration steady, avoids causing because Plasma Concentration is too high toxic side effect, reduces medicine frequency, the conformability that raising patient takes medicine etc.But there is the difficult problem that specific surface area is little, drug loading amount is little in hydroxyapatite nano particle.
Mesoporous material is the material of a class aperture at 2 ~ 50nm, and mesoporous material, owing to having larger specific surface area and pore volume, makes it have wide application potential in fields such as catalysis, absorption, hemostatic agent, sensings.What at present application was maximum is mesoporous silicon material, and the aperture high-sequential of mesoporous silicon nano material, specific surface area is large and be rich in hydroxyl activity group (OH), has been developed to a kind of novel degradable biological consistency pharmaceutical carrier.But mesoporous silicon is because of its difficult degradation, and degraded product is difficult to absorb, and makes its application be subject to larger restriction.
Mesoporous hydroxyapatite is because of its large specific surface area, and drug loading amount is large, simultaneously nano particle because of its size enough little, can be in the vascular system of human body free shuttling, finally can degrade, thereby be considered to a kind of carrier of good medicine.
At present, Chinese scholars adopts hydrothermal method to prepare porous hydroxyapatite, the mesoporous hydroxyapatite that adopts hydrothermal method to prepare, and its surface-area is less, and pore size distribution is inhomogeneous.The mesoporous hydroxyapatite that adopts the template synthesis that cetyl trimethylammonium bromide (CTAB) is template, the nanoparticle of preparation is club shaped structure, and length is in 500nm left and right, and larger nano-scale distributes, and is unfavorable for as pharmaceutical carrier.
Summary of the invention
The object of this invention is to provide that a kind of even aperture distribution, specific surface area are large, the preparation method of biocompatibility and the good mesoporous phosphorite nano particle of biological degradability, this nanoparticle can be applicable to pharmaceutical carrier, and a kind of preparation technology is provided.
The present invention adopts the mesoporous phosphorite nano particle of template synthesis, specifically comprises following step:
One, 1-5g F127 and 15-30g calcium pantothenate monohydrate are dissolved in the deionized water of 100-300g, violent stirring, until obtain clear milk sap, adds the expanding agent sym-trimethylbenzene solution of 10-30 ml, and mixing solutions continues to stir 6-12 hour.
Two, by 5.0-15.0g K 2hPO 43H 2o is dissolved in the deionized water of 50-150g, uses NH 3h 2o reconciles pH to 10-14.
Three, by the K of step 2 preparation 2hPO 4solution is slowly added drop-wise in the F127-calcium pantothenate mixing solutions of step 1 preparation, uniform stirring, and the mode reacting by heating system that adopts water-bath to reflux, control water bath heating temperature is 80-100 DEG C, return time is 24-48h.
Four, by above-mentioned solution filter, extracting waste throw out, vacuum-drying, controlling vacuum-drying temperature is 80-150 DEG C, the vacuum-drying time is 12-24 hour.
Five, dried white precipitate is carried out to low temperature presintering, control calcined temperature is 200-300 DEG C, and the pre-burning time is 2-6 hour.
Six, pre-burned white precipitate high-temperature calcination in retort furnace is removed to template, obtain mesoporous hydroxyapatite nano particle, control calcining temperature is 500-600 DEG C, and calcination time is 6-12 hour.
The present invention is taking triblock copolymer polyoxyethylene-poly-oxypropylene polyoxyethylene (F127) as template, add first expanding agent-sym-trimethylbenzene simultaneously, with template synthesis mesoporous aperture at 3-5nm, diameter is at the mesoporous hydroxyapatite nano particle of 50-100nm.
Tool of the present invention has the following advantages:
1, the mesoporous hydroxyapatite specific surface area of preparation is large, and drug loading amount is large, is a kind of good pharmaceutical carrier.
2, the hydroxyapatite nanometer distributions spherical in shape (size < 100nm) of preparation, even aperture distribution, can pass blood vessel and cell walls well as pharmaceutical carrier, arrives sick cell.
3, whole preparation technology is simple, can produce on a large scale.
Brief description of the drawings
Fig. 1 is infrared (FTIR) spectrogram of mesoporous hydroxyapatite nano particle
Fig. 2 is scanning electron microscope (SEM) picture of mesoporous hydroxyapatite nano particle;
Fig. 3 is transmission electron microscope (TEM) picture of mesoporous hydroxyapatite nano particle;
Fig. 4 is the nitrogen absorption/desorption isothermal curve of mesoporous hydroxyapatite nano particle;
Fig. 5 is the BJH graph of pore diameter distribution of mesoporous hydroxyapatite nano particle.
Embodiment
Below in conjunction with accompanying drawing, technical scheme of the present invention is further described; but be not limited to this; every technical solution of the present invention is modified or is equal to replacement, and not departing from the spirit and scope of technical solution of the present invention, all should be encompassed in protection scope of the present invention.
Embodiment 1:
The preparation method of the mesoporous hydroxyapatite nano particle that the present embodiment provides carries out according to the following steps:
One, 2.68g F127 and 17.67g calcium pantothenate monohydrate are dissolved in the deionized water of 100g jointly, violent stirring 2 hours, obtains clear milk sap; 12ml sym-trimethylbenzene solution is joined in above-mentioned mixing solutions, and limit edged stirs, and dropwises rear mixing solutions and continues to stir 6 hours.
Two, by 5.52g K 2hPO 43H 2o is dissolved in the deionized water of 66g, after stirring and dissolving, uses NH 3h 2o reconciles pH to 11.
Three, with separating funnel, by the K of 0.35mol/L 2hPO 4solution is slowly added drop-wise in F127-calcium pantothenate monohydrate mixing solutions, and uniform stirring by mixing solutions heating in water bath to 90 DEG C, refluxes 24 hours after dropwising.
Four, by cooling above-mentioned reacted solution rear suction filtration, extracting waste throw out, vacuum-drying 15 hours at 100 DEG C.
Five, by the pre-burning 2 hours at 250 DEG C in retort furnace of dried white precipitate.
Six, by pre-burned white precipitate in retort furnace 600 DEG C, calcine 8 hours.
Fig. 1 is infrared (FTIR) spectrogram of mesoporous hydroxyapatite nano particle, can see from Fig. 1,563 cm -1and 608 cm -1for PO in hydroxyapatite 4 3-flexural vibration absorb, 1030 cm -1for PO in hydroxyapatite 4 3-stretching vibration absorb, 3400 cm -1for OH in hydroxyapatite -absorption peak.
Fig. 2 is scanning electron microscope (SEM) picture of mesoporous hydroxyapatite nano particle, can see from Fig. 2, and nanoparticle state spherical in shape, diameter is about 100nm.
Fig. 3 is transmission electron microscope (TEM) picture of mesoporous hydroxyapatite nano particle, meso-hole structure as we can see from the figure.
Fig. 4 is the nitrogen absorption/desorption isothermal curve of mesoporous hydroxyapatite nano particle, wherein for the adsorption curve of mesoporous hydroxyapatite nano particle, along with the increase of dividing point, adsorptive capacity increases gradually, illustrates that its specific surface area is larger; for the adsorption curve of hydroxyapatite nano particle, along with the increase of dividing point, adsorptive capacity is substantially unchanged, illustrates that its adsorptive capacity is less, thereby proves to have synthesized the mesoporous hydroxyapatite nano particle of high-specific surface area.
Fig. 5 is the BJH graph of pore diameter distribution of mesoporous hydroxyapatite nano particle, and mesoporous aperture is in 5 nanometer left and right.
Embodiment 2:
The preparation method of the mesoporous hydroxyapatite nano particle that the present embodiment provides carries out according to the following steps:
One, 3.35g F127 and 22.43g calcium pantothenate monohydrate are dissolved in the deionized water of 200g jointly, violent stirring 3 hours, obtains clear milk sap; 16ml sym-trimethylbenzene solution is joined in above-mentioned mixing solutions, and limit edged stirs, and dropwises rear mixing solutions and continues to stir 8 hours.
Two, by 7.13g K 2hPO 43H 2o is dissolved in the deionized water of 130g, and magnetic agitation is used NH after dissolving 3h 2o reconciles pH to 13.
Three, with separating funnel, by the K of 0.30mol/L 2hPO 4solution is slowly added drop-wise in F127-calcium pantothenate monohydrate mixing solutions, and uniform stirring by mixing solutions heating in water bath to 95 DEG C, refluxes 28 hours after dropwising.
Four, by above-mentioned reacted solution suction filtration, obtain white depositions, at 120 DEG C, be dried 18 hours.
Five, by the pre-burning 3 hours at 280 DEG C in retort furnace of dried white precipitate.
Six, by pre-burned white precipitate in retort furnace 650 DEG C, calcine 10 hours.
Embodiment 3:
The preparation method of the mesoporous hydroxyapatite nano particle that the present embodiment provides carries out according to the following steps:
One, 3.92g F127 and 26.62g calcium pantothenate monohydrate are dissolved in the deionized water of 250g jointly, violent stirring 4 hours, obtains clear milk sap; 22ml sym-trimethylbenzene solution is joined in above-mentioned mixing solutions, and limit edged stirs, and dropwises rear mixing solutions and continues to stir 10 hours.
Two, by 11.26g K 2hPO 43H 2o is dissolved in the deionized water of 130g, and magnetic agitation is used NH after dissolving 3h 2o reconciles pH to 12.
Three, with separating funnel, by the K of 0.38mol/L 2hPO 4solution is slowly added drop-wise in F127-calcium pantothenate monohydrate mixing solutions, and uniform stirring by mixing solutions heating in water bath to 98 DEG C, refluxes 32 hours after dropwising.
Four, by cooling above-mentioned reacted solution rear suction filtration, obtain white depositions, at 150 DEG C, be dried 16 hours.
Five, by the pre-burning 4 hours at 300 DEG C in retort furnace of dried white precipitate.
Six, by pre-burned white precipitate in retort furnace 680 DEG C, calcine 12 hours.

Claims (8)

1. utilize a method for the high specific surface area and mesoporous hydroxyapatite nano particle of template synthesis, it is characterized in that described method steps is as follows:
One, 1-5g F127 and 15-30g calcium pantothenate monohydrate are dissolved in the deionized water of 100-300g, violent stirring, until obtain clear milk sap, adds the expanding agent of 10-30 ml, and mixing solutions continues to stir 6-12 hour;
Two, by 5.0-15.0g K 2hPO 43H 2o is dissolved in the deionized water of 50-150g, reconciles pH to 10-14;
Three, by the K of step 2 preparation 2hPO 4solution is slowly added drop-wise in the F127-calcium pantothenate mixing solutions of step 1 preparation, uniform stirring, the mode reacting by heating system that adopts water-bath to reflux;
Four, by above-mentioned solution filter, extracting waste throw out, vacuum-drying;
Five, dried white precipitate is carried out to low temperature presintering;
Six, pre-burned white precipitate high-temperature calcination in retort furnace is removed to template, obtain mesoporous hydroxyapatite nano particle.
2. the method for utilizing the high specific surface area and mesoporous hydroxyapatite nano particle of template synthesis according to claim 1, is characterized in that in described step 1, expanding agent is sym-trimethylbenzene.
3. the method for utilizing the high specific surface area and mesoporous hydroxyapatite nano particle of template synthesis according to claim 1, is characterized in that, in described step 2, using NH 3h 2o reconciles pH to 10-14.
4. the method for utilizing the high specific surface area and mesoporous hydroxyapatite nano particle of template synthesis according to claim 1, is characterized in that in described step 3, water bath heating temperature is 80-100 DEG C, and return time is 24-48h.
5. the method for utilizing the high specific surface area and mesoporous hydroxyapatite nano particle of template synthesis according to claim 1, is characterized in that in described step 4, vacuum-drying temperature is 80-150 DEG C, and the vacuum-drying time is 12-24 hour.
6. the method for utilizing the high specific surface area and mesoporous hydroxyapatite nano particle of template synthesis according to claim 1, is characterized in that in described step 5, calcined temperature is 200-300 DEG C, and the pre-burning time is 2-6 hour.
7. the method for utilizing the high specific surface area and mesoporous hydroxyapatite nano particle of template synthesis according to claim 1, is characterized in that in described step 6, calcining temperature is 500-600 DEG C, and calcination time is 6-12 hour.
8. the method for utilizing the high specific surface area and mesoporous hydroxyapatite nano particle of template synthesis according to claim 1, the mesoporous aperture that it is characterized in that described mesoporous hydroxyapatite nano particle is 3-5nm, diameter is 50-100nm.
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104548108A (en) * 2015-02-02 2015-04-29 哈尔滨工业大学 Preparation method of mesoporous apatite nano drug carrier with pH responsive core-shell structure
CN104587488A (en) * 2015-02-02 2015-05-06 哈尔滨工业大学 Preparation method of mesoporous apatite nano-drug carrier with pH responsiveness and cellular targeting property for hepatoma cell
CN104587473A (en) * 2015-02-02 2015-05-06 哈尔滨工业大学 Preparation method of mesoporous apatite nano-drug carrier with reduction responsiveness and cellular targeting property for hepatoma cell
CN107670494A (en) * 2017-08-23 2018-02-09 石家庄铁道大学 A kind of mesoporous titanium apatite and its preparation method and application
CN108295877A (en) * 2017-09-01 2018-07-20 石家庄铁道大学 A kind of halogenation oxygen bismuth/POROUS TITANIUM hydroxyapatite composite material and its preparation method and application

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101143718A (en) * 2007-08-30 2008-03-19 天津大学 Method for preparing crystallinity controllable nano hydroxyapatite powder
CN102583286A (en) * 2011-01-11 2012-07-18 沈阳药科大学 Porous hydroxyapatite and preparation method and application thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101143718A (en) * 2007-08-30 2008-03-19 天津大学 Method for preparing crystallinity controllable nano hydroxyapatite powder
CN102583286A (en) * 2011-01-11 2012-07-18 沈阳药科大学 Porous hydroxyapatite and preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
FANYAN ZENG ET AL.: "Preparation of pore expanded mesoporous hydroxyapatite via auxiliary solubilizing template method", 《COLLOIDS AND SURFACES A: PHYSICOCHEMICAL AND ENGINEERING ASPECTS》, vol. 441, 16 October 2013 (2013-10-16), pages 737 - 743, XP028793806, DOI: doi:10.1016/j.colsurfa.2013.10.028 *
Y.F.ZHAO ET AL.: "Triblock co-polymer templating synthesis of mesostructured hydroxyapatite", 《MICROPOROUS AND MESOPOROUS MATERIALS》, vol. 87, 19 September 2005 (2005-09-19), pages 110 - 117, XP027704964 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104548108A (en) * 2015-02-02 2015-04-29 哈尔滨工业大学 Preparation method of mesoporous apatite nano drug carrier with pH responsive core-shell structure
CN104587488A (en) * 2015-02-02 2015-05-06 哈尔滨工业大学 Preparation method of mesoporous apatite nano-drug carrier with pH responsiveness and cellular targeting property for hepatoma cell
CN104587473A (en) * 2015-02-02 2015-05-06 哈尔滨工业大学 Preparation method of mesoporous apatite nano-drug carrier with reduction responsiveness and cellular targeting property for hepatoma cell
CN104548108B (en) * 2015-02-02 2017-06-20 哈尔滨工业大学 A kind of preparation method of the mesoporous apatite nano-medicament carrier of pH responses core shell structure
CN104587488B (en) * 2015-02-02 2017-10-03 哈尔滨工业大学 A kind of preparation method of the mesoporous apatite nano-medicament carrier to liver cancer cells with pH responses and cell-targeting
CN107670494A (en) * 2017-08-23 2018-02-09 石家庄铁道大学 A kind of mesoporous titanium apatite and its preparation method and application
CN107670494B (en) * 2017-08-23 2020-03-17 石家庄铁道大学 Mesoporous titanium apatite and preparation method and application thereof
CN108295877A (en) * 2017-09-01 2018-07-20 石家庄铁道大学 A kind of halogenation oxygen bismuth/POROUS TITANIUM hydroxyapatite composite material and its preparation method and application
CN108295877B (en) * 2017-09-01 2020-07-21 石家庄铁道大学 Bismuth oxyhalide/porous titanium hydroxyapatite composite material and preparation method and application thereof

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