CN104628045A - Large-scale preparation method of controllable-quality clinic-grade magnetic nanoparticles - Google Patents
Large-scale preparation method of controllable-quality clinic-grade magnetic nanoparticles Download PDFInfo
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- CN104628045A CN104628045A CN201510070658.4A CN201510070658A CN104628045A CN 104628045 A CN104628045 A CN 104628045A CN 201510070658 A CN201510070658 A CN 201510070658A CN 104628045 A CN104628045 A CN 104628045A
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Abstract
The invention relates to a large-scale preparation method of controllable-quality clinic-grade magnetic nanoparticles. The organic iron salt and inorganic iron salt are combined, ascorbic acid is added, and a hydrothermal process is utilized to prepare the ferroferric oxide magnetic nanoparticles with small size, favorable water solubility and excellent magnetic properties. Compared with the prior art, the preparation method is simple and quick, and can directly prepare the high-water-solubility magnetic nanoparticles with the average size of 5-8nm; and the magnetic nanoparticles have the advantages of uniform particle size distribution and favorable biocompatibility since carboxyl group (-COOH) and other organic groups are carried on the surface.
Description
Technical field
The present invention relates to the preparation field of nano material, be specifically related to a kind of scale manufacturing technique and quality controlling means of clinical grade magnetic nano-particle.
Background technology
China finds magnetic phenomenon country the earliest, and very early magnetic substance is introduced the treatment field of disease, just has magnetite can the theory of " suppressing hyper-yang to enchance respiration, tranquillizing the mind by relieving convulsion " in Traditional Chinese Medicine.Along with medical technology and the development of magnetic theory in modern times, the application of magneticsubstance in medical science also enters a new developing period.Especially current people constantly deepen the research that nano material is applied in biomedicine, all have a wide range of applications at field nano magnetic materials such as target administration, image checking, tumor thermotherapies.
Prepare magnetic Nano material and have multiple method at present, comprise physical preparation method, as high-energy mechanical ball milling method, physical vaporous deposition; Chemical preparation process, as microemulsion method, high-temperature decomposition etc.But obtained magnetic nano-particle, size, homogeneity, water-soluble etc. in be still difficult to accomplish fully up to expectations.In order to improve the water-soluble of magnetic nano-particle, and giving full play to its application potential at biomedical sector, general needs introduces carboxyl (-COOH), the amino functional group such as (-NH2), sulfydryl (-SH) in magnetic nano particle sub-surface.Carrying difference in functionality group magnetic nano-particle by combining from biologically active substances such as different biomacromolecules, just can show different functional performance.Such as, containing a large amount of amino in antibody protein molecule, can there is linked reaction in amino and carboxyl under certain conditions.Therefore surface carry carboxyl magnetic nano-particle just by the linked reaction of carboxyamino with antibodies together with, form immunomagnetic beads, be applied in the susceptibility that can increase substantially detection technique in immunochromatography detection.
Summary of the invention
Object of the present invention is exactly provide a kind of quality controllable large-scale preparation method of clinical grade magnetic nano-particle to overcome defect that above-mentioned prior art exists.
Object of the present invention can be achieved through the following technical solutions: a kind of quality controllable large-scale preparation method of clinical grade magnetic nano-particle; it is characterized in that; the method selects organic molysite and inorganic molysite to combine; and add xitix, utilize that hydrothermal method preparation size is little, the ferroferric oxide magnetic nano-particles of good water solubility, magnetic property excellence.
Described method specifically comprises the following steps:
(1) take a certain proportion of organic molysite and inorganic molysite, be dissolved in respectively in deionized water, stir with the speed of 200 ~ 500rpm/min and make it fully dissolve;
(2) by two parts of obtained for step (1) solution mixing, continue to stir with the speed of 200 ~ 500rpm/min, make it fully mix;
(3) take a certain amount of xitix, make itself and Fe
3+the mol ratio of ion is 1:3 ~ 9, adds in the mixing solutions that step (2) obtains, continues to stir with the speed of 200 ~ 500rpm/min;
(4) pH value to 9 ~ 12 of mixing solutions that obtain of regulating step (3), continue to stir 5 ~ 30min with the speed of 200 ~ 500rpm/min;
(5) mixing solutions that step (4) obtains is transferred in hydrothermal reaction kettle, with the temperature 4 ~ 15h of 150 ~ 230 DEG C;
(6) solution that step (5) obtains is transferred in dialysis tubing, dialyses 1 ~ 2 day, with postlyophilization, target ferroferric oxide magnetic nano-particles can be obtained.
Described organic molysite comprises and is not limited to ironic citrate, ferric acetyl acetonade, Iron Dextran, Ferrous Gluconate.
Described inorganic molysite comprises and is not limited to ferrous sulfate, ferric sulfate, iron protochloride, iron(ic) chloride.
From above-mentioned organic molysite and inorganic molysite, respectively selecting a kind, making the addition of organic molysite described in step (1) and inorganic molysite for making Fe
2+and Fe
3+mol ratio 1:1 ~ 4.
Step (4) adopts the sodium hydroxide solution of 0.4 ~ 5M to regulate the pH concentration of mixing solutions.
Traditional single dispersing high-quality magnetic nano-particle synthesis yardstick is mostly in milligram rank, if improve synthesis yardstick, subject matter is that magnetic nano-particle particle diameter, pattern and magnetic intensity can not get effective control, and the synthetic method that the present invention proposes carries out pattern and dispersed control mainly through atom/molecule yardstick to presoma, namely adopt organic molysite and inorganic molysite as presoma simultaneously, and add xitix, thus ensure that presoma dispersion, assembling, thermal decomposition process and the final forming process of magnetic particle.Only use inorganic molysite as presoma compared to traditional method, organic molysite not only provides reaction necessary iron ion, the mode of its organic ion negatively charged ion also by chemical bonding under hydrothermal reaction condition is connected to magnetic particle surface, improves the water-soluble and functional of magnetic particle.And xitix is also known as vitamins C, be the requisite nutrient substances of other many animals such as human body, mainly play a kind of oxidation resistant effect in vivo.Xitix is introduced reaction system, and under high-temperature water heat condition, xitix plays the effect of reductive agent, makes part Fe
3+ion is reduced to Fe
2+ion, contributes to the formation of ferroferric oxide magnetic nano-particles; Also make magnetic nano particle sub-surface connect upper carboxyl by chemical bonding simultaneously, further enhancing the water-soluble and functional of magnetic nano-particle.Gram level yardstick mass-producing synthesis high-quality magnetic nano-particle needs to improve consolidating of hydro-thermal reaction system and contains; traditional preparation technology's solid content is all relatively less (<1%); and present method is solid containing at present can about >5%; synthesis yardstick significantly improves, and the particle diameter of magnetic nano-particle, pattern, dispersiveness and magnetic intensity can be effectively controlled.
Compared with prior art, the present invention has following characteristics:
1. preparation is simple, quick, synthesis yardstick is large, only a small amount of several reagent need be used to obtain.
2. can directly obtain water-soluble good magnetic nano-particle, without the need to subsequent operationss such as phase inversions.
3. obtained ferroferric oxide magnetic nano-particles mean sizes is 5 ~ 8nm, and even particle size distribution.
4. the organic groups such as carboxyl (-COOH) are carried on surface, good biocompatibility.
Accompanying drawing explanation
Fig. 1 is the transmission electron microscope picture of ferroferric oxide magnetic nano-particles;
Fig. 2 is the high-resolution-ration transmission electric-lens picture of ferroferric oxide magnetic nano-particles;
Fig. 3 is the Fourier transform infrared spectroscopy spectrogram of ferroferric oxide magnetic nano-particles.
Embodiment
Below in conjunction with the drawings and specific embodiments, the present invention is described in detail.
The hydro-thermal preparation of embodiment 1 ferroferric oxide magnetic nano-particles
(1) take ironic citrate and ferrous sulfate that mol ratio is 1:2, be dissolved in 20mL deionized water respectively, stir with the speed of 400rpm/min and make it fully dissolve.
(2) by two parts of obtained for step (1) solution mixing, continue to stir with the speed of 400rpm/min, make it fully mix.
(3) take 0.1g xitix, add in the mixing solutions that step (2) obtains, continue to stir with the speed of 400rpm/min.
(4) the mixed solution and dripping concentration obtained to step (3) is the sodium hydroxide solution of 0.4M, regulates the pH value to 10 of this mixing solutions, continues to stir 10min with the speed of 400rpm/min.
(5) mixing solutions that step (4) obtains is transferred in hydrothermal reaction kettle, with the temperature 10h of 200 DEG C.
(6) solution that step (5) obtains is transferred in dialysis tubing, dialyses 2 days, with postlyophilization, target ferroferric oxide magnetic nano-particles can be obtained.
As shown in Figure 1, high-resolution-ration transmission electric-lens picture as shown in Figure 2, can find out that obtained ferroferric oxide magnetic nano-particles mean sizes is 5 ~ 8nm to the transmission electron microscope picture of gained ferroferric oxide magnetic nano-particles, and even particle size distribution.
The Fourier transform infrared spectroscopy spectrogram of gained ferroferric oxide magnetic nano-particles as shown in Figure 3, can be found out, 1631cm
-1and 1385cm
-1the absorption peak of position can be classified as the flexible and symmetrical stretching vibration of the unsymmetrically of carboxylic acid ion, and surface magnetism nanoparticle surface carries the organic groups such as carboxyl (-COOH), good biocompatibility.
Embodiment 2
A quality controllable large-scale preparation method for clinical grade magnetic nano-particle, specifically comprises the following steps:
(1) take a certain proportion of ferric acetyl acetonade and iron protochloride, be dissolved in 10mL deionized water respectively, stir with the speed of 200rpm/min and make it fully dissolve;
(2) by two parts of obtained for step (1) solution mixing, Fe is made
2+and Fe
3+mol ratio 1:1, continue to stir with the speed of 200rpm/min, make it fully mix;
(3) take a certain amount of xitix, make itself and Fe
3+the mol ratio of ion is 1:3, adds in the mixing solutions that step (2) obtains, continues to stir with the speed of 200rpm/min;
(4) pH value to 9 of the mixing solutions adopting the sodium hydroxide solution regulating step (3) of 0.4M to obtain, continues to stir 5min with the speed of 200rpm/min;
(5) mixing solutions that step (4) obtains is transferred in hydrothermal reaction kettle, with the temperature 4h of 150 DEG C;
(6) solution that step (5) obtains is transferred in dialysis tubing, dialyses 1 ~ 2 day, with postlyophilization, target ferroferric oxide magnetic nano-particles can be obtained.
Embodiment 3
A quality controllable large-scale preparation method for clinical grade magnetic nano-particle, specifically comprises the following steps:
(1) take a certain proportion of Ferrous Gluconate and ferric sulfate, be dissolved in 25mL deionized water respectively, stir with the speed of 500rpm/min and make it fully dissolve;
(2) by two parts of obtained for step (1) solution mixing, Fe is made
2+and Fe
3+mol ratio 1:4, continue to stir with the speed of 500rpm/min, make it fully mix;
(3) take a certain amount of xitix, make itself and Fe
3+the mol ratio of ion is 1:9, adds in the mixing solutions that step (2) obtains, continues to stir with the speed of 500rpm/min;
(4) pH value to 12 of the mixing solutions adopting the sodium hydroxide solution regulating step (3) of 5M to obtain, continues to stir 30min with the speed of 500rpm/min;
(5) mixing solutions that step (4) obtains is transferred in hydrothermal reaction kettle, with the temperature 15h of 230 DEG C;
(6) solution that step (5) obtains is transferred in dialysis tubing, dialyses 1 ~ 2 day, with postlyophilization, target ferroferric oxide magnetic nano-particles can be obtained.
Claims (6)
1. the quality controllable large-scale preparation method of a clinical grade magnetic nano-particle; it is characterized in that; the method selects organic molysite and inorganic molysite to combine; and add xitix, utilize that hydrothermal method preparation size is little, the ferroferric oxide magnetic nano-particles of good water solubility, magnetic property excellence.
2. the quality controllable large-scale preparation method of a kind of clinical grade magnetic nano-particle according to claim 1, it is characterized in that, described method specifically comprises the following steps:
(1) take a certain proportion of organic molysite and inorganic molysite, be dissolved in respectively in deionized water, stir with the speed of 200 ~ 500rpm/min and make it fully dissolve;
(2) by two parts of obtained for step (1) solution mixing, continue to stir with the speed of 200 ~ 500rpm/min, make it fully mix;
(3) take a certain amount of xitix, make itself and Fe
3+the mol ratio of ion is 1:3 ~ 9, adds in the mixing solutions that step (2) obtains, continues to stir with the speed of 200 ~ 500rpm/min;
(4) pH value to 9 ~ 12 of mixing solutions that obtain of regulating step (3), continue to stir 5 ~ 30min with the speed of 200 ~ 500rpm/min;
(5) mixing solutions that step (4) obtains is transferred in hydrothermal reaction kettle, with the temperature 4 ~ 15h of 150 ~ 230 DEG C;
(6) solution that step (5) obtains is transferred in dialysis tubing, dialyses 1 ~ 2 day, with postlyophilization, target ferroferric oxide magnetic nano-particles can be obtained.
3. the quality controllable large-scale preparation method of a kind of clinical grade magnetic nano-particle according to claim 2, is characterized in that, described organic molysite comprises and is not limited to ironic citrate, ferric acetyl acetonade, Iron Dextran, Ferrous Gluconate.
4. the quality controllable large-scale preparation method of a kind of clinical grade magnetic nano-particle according to claim 2, is characterized in that, described inorganic molysite comprises and is not limited to ferrous sulfate, ferric sulfate, iron protochloride, iron(ic) chloride.
5. the quality controllable large-scale preparation method of a kind of clinical grade magnetic nano-particle according to claim 2, is characterized in that, the organic molysite described in step (1) and the addition of inorganic molysite are for making Fe
2+and Fe
3+mol ratio 1:1 ~ 4.
6. the quality controllable large-scale preparation method of a kind of clinical grade magnetic nano-particle according to claim 2, is characterized in that, step (4) adopts the sodium hydroxide solution of 0.4 ~ 5M to regulate the pH concentration of mixing solutions.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105641717A (en) * | 2016-01-21 | 2016-06-08 | 上海交通大学 | Hyperstable monodisperse fluorescent magnetic nano probe and preparation and application thereof |
| CN105931774A (en) * | 2016-05-06 | 2016-09-07 | 西北师范大学 | Method for preparing ferroferric oxide/graphene oxide-like magnetic nanocomposite by taking ferrous gluconate as single raw material |
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| CN101665271A (en) * | 2009-09-23 | 2010-03-10 | 西北大学 | Preparation method of single metal-doped modified clustered nanometer ferroferric oxide hydrogen storage material |
| CN102275998A (en) * | 2011-05-30 | 2011-12-14 | 北京理工大学 | Preparation method of magnetic Fe3O4 nanoparticles and application thereof in adsorption and separation of heavy metal ions |
| CN104058465A (en) * | 2014-07-21 | 2014-09-24 | 济南大学 | Ferroferric oxide hollow polyhedral particle and preparation method thereof |
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- 2015-02-10 CN CN201510070658.4A patent/CN104628045A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004359505A (en) * | 2003-06-05 | 2004-12-24 | Bridgestone Corp | Method for manufacturing magnetic nanoparticle, and magnetic nanoparticle |
| CN101665271A (en) * | 2009-09-23 | 2010-03-10 | 西北大学 | Preparation method of single metal-doped modified clustered nanometer ferroferric oxide hydrogen storage material |
| CN102275998A (en) * | 2011-05-30 | 2011-12-14 | 北京理工大学 | Preparation method of magnetic Fe3O4 nanoparticles and application thereof in adsorption and separation of heavy metal ions |
| CN104058465A (en) * | 2014-07-21 | 2014-09-24 | 济南大学 | Ferroferric oxide hollow polyhedral particle and preparation method thereof |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105641717A (en) * | 2016-01-21 | 2016-06-08 | 上海交通大学 | Hyperstable monodisperse fluorescent magnetic nano probe and preparation and application thereof |
| CN105641717B (en) * | 2016-01-21 | 2019-01-18 | 上海交通大学 | The overstable monodispersed fluorescence magnetic nano-probe of one kind and its preparation and application |
| CN105931774A (en) * | 2016-05-06 | 2016-09-07 | 西北师范大学 | Method for preparing ferroferric oxide/graphene oxide-like magnetic nanocomposite by taking ferrous gluconate as single raw material |
| CN105931774B (en) * | 2016-05-06 | 2018-04-13 | 西北师范大学 | The method that ferroso-ferric oxide/class graphene oxide magnetic nanometer composite material is prepared using ferrous gluconate as single raw material |
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