CN101935070A - Method for synthesizing superparamagnetic ferroferric oxide nano particle in situ by induction of acrylic acid polymer nano hydrogel - Google Patents
Method for synthesizing superparamagnetic ferroferric oxide nano particle in situ by induction of acrylic acid polymer nano hydrogel Download PDFInfo
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Abstract
The invention relates to a method for synthesizing a superparamagnetic ferroferric oxide nano particle in situ by the induction of acrylic acid polymer nano hydrogel, which comprises the following steps of: with hydroxypropyl cellulose in an aqueous solution as a template, synthesizing biodegradable acrylic acid polymer nano hydrogel at first, wherein the alkali neutralized acrylic acid polymer nano hydrogel contains a great amount of negative -COO<->; adsorbing a great amount of positive Fe<2+> to enter a gel network by the interaction of static electricity; and with a gel particle as a nano reactor, internally synthesizing a ferroferric oxide nano particle in situ. The operating method of the invention is simple, convenient and easy, the prepared ferroferric oxide magnetic nano particle have favorable dispersity and intelligence, and a ferroferric oxide nano crystal has even distribution and high content in the nano hydrogel magnetic nano particle.
Description
Technical field
The invention belongs to the preparation field of superparamagnetism ferriferrous oxide nano-particle, particularly a kind of method of acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle.
Background technology
Bio-imaging has become a frontier that increases fast, and its importance shows basic biology and medical scientific domain.In recent years, owing to uniqueness analysis and diagnosis capability in molecule and cell level, biomedical imaging causes worldwide extensive concern.As a result, the new discipline " molecular imaging " of a kind of binding molecule biology and in-vivo imaging arises at the historic moment.Representational imaging technique comprises computerize X-light tomography shooting (CT), optical imagery, nuclear magnetic resonance, positron emission tomography (PET), single photon emission computed fault imaging (SPECT), and ultra sonic imaging.The interaction of cell function and molecule during these imaging techniques can lively be observed the interior various organs of human body and organize, what is more important, image-forming diagnose can be to the infringement that causes of human body.They can help early diagnosis such as the cancer and the cardiovascular and cerebrovascular diseases of disease.
Nuclear magnetic resonance has been brought into play effect of crucial importance at aspects such as human brain and nervus centralis imaging, assess cardiac function, detection tumour and cardiovascular and cerebrovascular diseases.Although nuclear magnetic resonance itself can present detailed image, because difference time of relaxation of normal tissue and injured tissues is less, the image of therefore normal tissue and injured tissues is difficult to differentiate.In order to address this problem, be known as the image that magnetic compound can help to differentiate normal tissue and injured tissues that has of " contrast medium " (Contrast agent).The contrast medium inductive is strengthened picture intelligence from the interaction of contrast medium with contiguous water proton, promptly is close to the water proton change of time of relaxation.According to the ultimate principle of nuclear magnetic resonance, two kinds of lax patterns are arranged: (1) vertically the horizontal T2 of T1 lax (2) is lax.According to two kinds of lax patterns, contrast medium is divided into T1 and two kinds of contrast medium of T2.The normally paramagnetic mixture of T1 contrast medium, the most representational T1 contrast medium is a Gd coordination compound; The most representational T2 contrast medium is the nanoparticle of the iron oxides of superparamagnetism.
At present, the contrast medium that China uses mostly is import and the homemade gadolinium contrast medium that contains, and still, contains the gadolinium contrast medium and has higher toxic side effect.U.S. food Drug Administration (FDA) sends announcement on the website in May, 2007, require enterprise that all are contained gadolinium nuclear magnetic resonance (MRI) contrast medium (hereinafter to be referred as containing the gadolinium contrast medium) and add a new black surround warning, warning has the Insufficient patient's use of severe renal to contain the gadolinium contrast medium kidney of generation source property system fiber (Nephrogenic SystemicFibrosis, risk NSF) is arranged.State Food and Drug Administration's adverse drug reaction communication on October 29th, 2007 (the 13rd phase) issue " is watched out for and is contained the kidney source property system fiberization that the gadolinium magnetic resonance contrast agent causes ".
Cause visual darkness to be deepened thereby the nanoparticle T2 contrast medium of the iron oxides of superparamagnetism shortens time of relaxation, be negative sense picture intelligence clearly.Compare with T1 type Gd coordination compound contrast medium, superparamagnetic nanoparticle can improve the relaxation velocity of ambient water proton more effectively, and theoretical and test shows that all the superparamagnetic nanoparticle of nanometer volumetric molar concentration can measure the influence of the relaxation velocity of water proton; And superparamagnetic nanoparticle has good Bc in human body.Ferroferric oxide magnetic nano-particles toxicity is low, has magnetic responsiveness.When diameter reaches its magnetic single domain size, will show superparamagnetism, promptly can in more weak foreign field, produce huge magnetic, and after foreign field was cancelled, the magnetic of particle disappeared thereupon also.The superparamagnetism ferroferric oxide nano granules has potential because having superparamagnetism and biological degradability at cellular segregation, targeted drug release, nuclear magnetic resonance (MRI) and tumour magnetic target thermotherapy biomedical sectors such as (MTH) and uses.
Since the last century the eighties, the nanoparticle of the iron oxides of superparamagnetism has been obtained great progress as the research and the biomedical applications of contrast medium.One of important research direction of MRI contrast medium is contrast medium and the blood pond contrast medium that development has organ, tissue target tropism in the world.According to the nanoparticle of the iron oxides of superparamagnetism and the formed size of thickness of coating, the nanoparticle of this type has different purposes: (1) size range is used for the gi tract imaging between 300nm to the nanoparticle of 3.5 μ m; (2) between the 150nm, the nanoparticle of injection is discharged to kidney and spleen by the reticuloendothelium system to size apace between 60nm, so the nanoparticle of this class size is used for the imaging in kidney and the spleen; (3) size is less than 50nm, the nanoparticle of injection is longer than the nanoparticle of large-size the cycling time in blood, and undersized nanoparticle can pass wall capillaceous, usually absorbed, so the nanoparticle of this class size is used for the imaging in lymphoglandula and the marrow by lymphoglandula and marrow.
The research of the nanoparticle contrast agent of the iron oxides of superparamagnetism is mainly aspect three: (1) strengthens the nanoparticle of the iron oxides of picture intelligence effect; (2) promote nanoparticle dispersive hydrophilic macromolecule coating layer in water; (3) compound of the biologically active that is connected with the polymer coating layer, these compounds are with contrast medium target goal position.The research of the synthetic and performance of the nanoparticle of iron oxides is comparatively ripe, but how the clad nano particle improves the performance of contrast medium and be of many uses, remains the research direction that attracts people's attention.The nanoparticle of iron oxides has hydrophobic surface, owing to interacting to assemble, hydrophobic in water forms big particle even precipitation, equally, in human body, show unstable, therefore, need to adopt aqueous high molecular clad nano particle to make it keep stable in water and in the human body with Bc.Recent two decades comes, numerous in the world scientific research institutions and company have carried out extensively and in depth research and have developed several superparamagnetism magnetite (Fe3O4) nanoparticle contrast agents superparamagnetism magnetite nano particle contrast medium, obtain united States food and drug administration's approval and use.U.S. Advanced Magnetics, Inc. company has taken the lead in inventing magnetite nano particle (diameter 80-150nm) contrast medium of reagent name AMI-25, they have studied the toxicity of AMI-25 from acute toxicity, subacute toxicity and three aspects of mutagenicity, the result shows equal nontoxicity, and AMI-25 has been used for the contrast medium of human body kidney and position, spleen; Other two kinds of contrast medium AMI-121 and AMI-227 have also invented in the said firm, the AMI-121 nanoparticle is directly through being approximately 300nm, coat directly by the siloxanes polymer that 10nm magnetite nano particle forms through being about, in order in water medium, to stablize non-hydrophilic AMI-121 nanoparticle, the thickening material that forms with starch and Mierocrystalline cellulose is as the stablizer of nanoparticle, and this kind contrast medium is by united States food and drug administration's approval human gastrointestinal tract imaging; AMI-227 coats with dextran (dextran) and directly constitutes through the 4-6nm ferriferrous oxide nano-particle, directly through being approximately 20-40nm, by intravenous methods, is used for lymphoglandula position image-forming contrast medium.In addition, contrast medium has been invented by German Bayer company
Directly through being approximately 60nm, it forms by carboxyl dextran (carboxydextran) coated ferriferrous oxide nanoparticle its particle, and is national as human body kidney and position, spleen contrast medium in Europe, Japan, Australia etc.
Above-mentioned ferriferrous oxide nano-particle contrast medium skin just promotes particle to disperse and stable polymer, lacks the molecule ligand with guide effect, therefore, contrast medium in vivo the imaging position mainly by the physiological process of nature guiding.For illness in the positioning body more accurately and carry out early diagnosis and therapy, at first need introduce the ligand (ligand) of biologically active on the nanoparticle macromolecule surface, these cooperate physical efficiencys that the contrast medium guiding illness tissue of q.s or its are carried out image-forming diagnose on every side.
In recent years, the ferriferrous oxide nano-particle contrast medium that the has target in the world research that is used for cancer and cardiovascular and cerebrovascular diseases early diagnosis has obtained major progress.Scientists finds that formed contrast medium can be absorbed fast and effectively by cancer cells by connecting Transferrins,iron complexes (transferring) or folate (folate) on the nanoparticle contrast agent surface, therefore obtains the cancer cells magnetic resonance image (MRI); Diagnosing atherosclerotic, thrombus, three kinds of cardiovascular disorder aspects of myocardial infarction in early days, the ferriferrous oxide nano-particle contrast medium that can lead is used for nuclear magnetic resonance and has brought into play vital role.Be connected with the contrast medium surface as blood vessel bonding molecule-1 (vascularadhesion molecule-1), make to be diagnosed in the atherosclerosis position; (arginine-glycine-aspartate acid peptide RGD) is keyed to the contrast medium surface, can form the magnetic resonance image (MRI) at thrombus position as the ligand arginine-glycine-Dong propylhomoserin peptide of target; The surface has antimyosin (Antimyosin) as the orientable arrival myocardial infarction of the contrast medium of target ligand position, thereby produces magnetic resonance image (MRI).For the reactive chemical functional group who connects biologically active ligand is provided, after deliberation several water-soluble polymer coated ferriferrous oxide nanoparticles with biocompatibility, these polymers comprise dextran (Dextran), carboxyl dextran (Carboxydextran), chitosan (Chitosan), polyoxyethylene glycol (PEG), polyvinyl alcohol (PVA), polyacrylic acid (PAA).As contrast medium, require polymer to coat process and can not introduce any deleterious compound, tensio-active agent, and organic solvent.Usually adopt in polymer aqueous solution co-precipitation original position to coat and polymer coats two kinds of main method of back coating of established ferriferrous oxide nano-particle.The result shows that the nanoparticle of coating not only has satisfactory stability, and can circulate in blood the long time, and further these polymers can provide the reactive chemical functional group who connects biologically active ligand.
At present, method for coating commonly used mainly is divided in the polymer aqueous phase solution and coats ready-made two kinds of methods of ferriferrous oxide nano-particle after the co-precipitation coating and polymer, though can to a certain degree improve the stability and the cycling time in blood thereof of nanoparticle, but still have three subject matters: homogeneity of (1) coated iron oxide content and the homogeneity that coats the nanoparticle that forms; (2) the nanoparticle interphase interaction power of polymer and iron oxides a little less than, so the stability of polymer coated iron oxide is not high; (3) in the nanoparticle of single coating, the content of martial ethiops is not high, causes in some environment of human body, and the picture intelligence that contrast medium forms is unintelligible.
And the employing chitosan gel rubber original position of mentioning among the patent CN101113022A is induced the method for coated ferriferrous oxide nanoparticle, be chitosan gel rubber repeatedly to be immersed in realize in the molysite aqueous solution that original position coats, rather than attract the iron ion original position synthetic by electrostatic interaction in gel particles inside.And chitosan gel rubber is to adopt to contain virose organic crosslinking agent, does not therefore have biocompatibility.Patent CN 101612541A, though also be to coat with polyacrylic acid to be used for the cell DNA separation and purification, the high-temperature decomposition that adopts needs relatively harsher reaction conditions, as high temperature, protective atmosphere etc., and needs through numerous and diverse program such as refluxing, centrifugal.
Nano-hydrogel is meant that diameter is at the tens macromolecule hydrogel microballoons to the hundreds of nanometer, because the surface-area of its minimum size, super large (1 gram diameter is that the total surface area of the Nano microsphere of 100 nanometers is approximately 60 square metres), compare the external environment inductive pucker ﹠ bloat that the nano-hydrogel performance is exceedingly fast with general hydrogel.Potential application with nano-hydrogel of Bc almost spreads all over each great field, as various bacteriums and other the deleterious impurity in identification and removing water and the food, improve the production efficiency of oil, the separation of protein and DNA and purifying, coat and carry gene and biopharmaceutical macromolecular drug and be used for the treatment of cancer and acquired immune deficiency syndrome (AIDS), the matrix of the injectable human tissue engineering of non-operation, coat a large amount of magnetic metal ions and be used for the one-tenth shadow reagent (MRI Contrast Agent) and the nano biological sensor of novel nucleus magnetic resonance, cause world wide internal medicine scholar's strong interest day by day.
Summary of the invention
Technical problem to be solved by this invention provides a kind of method of acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle, working method of the present invention is simple and easy to do, prepared ferroferric oxide magnetic nano-particles has good dispersiveness and intelligent, in the nano-hydrogel magnetic nano-particle, ferroferric oxide nano crystal is evenly distributed and the content height.
The method of a kind of acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle of the present invention comprises:
(1) under the room temperature hydroxypropylcellulose HPC powder is dissolved in deionized water and magnetic agitation 1～5 day, the homogeneous phase solution that is mixed with 1wt%～10wt% is as standby;
(2) the above-mentioned HPC solution that is mixed with of 5～10g, 0.1g linking agent are dissolved in 87.8～93.8g deionized water and magnetic agitation 15～60min together;
(3) add 0.05g initiator, 1～2g acrylic monomer and stir 15～60min at the nitrogen protection lower magnetic force;
(4) temperature of reaction rises to 20～40 ℃ and add 0.05g accelerator initiated polymerization;
(5) the acrylic polymers nano-hydrogel that makes is transferred to pH=6～8 with alkali, and dialysed 1～3 day;
(6) after 1～10 times of the dilution of the acrylic polymers nano-hydrogel after will dialysing, add 0.6～1.5gFeSO
47H
2The O powder stirs the whole night at the nitrogen protection lower magnetic force, and dialysed 1～3 day;
(7) under nitrogen protection, add 0.03～0.12g reductive agent and stir 2h; add 4.49～20.96g ammoniacal liquor; when solution becomes black by green; stopped reaction; take out dialysis 1～3 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of acrylic polymers nano-hydrogel original position coating modification.
The molecular-weight average of the hydroxypropylcellulose in the described step (1) is M
w=1.0 * 10
3～1.0 * 10
6
Linking agent in the described step (2) is N, N '-methylene-bisacrylamide Bis, polyoxyethylene glycol PEG, oxyacetic acid β-ester or (polyethylene glycol-lactic acid-polyoxyethylene glycol) diacrylate.
Initiator in the described step (3) is ammonium persulphate APS or Potassium Persulphate KPS, and acrylic monomer is acrylic or methacrylic acid.
Accelerator in the described step (4) is Tetramethyl Ethylene Diamine TEMED or S-WAT.
Alkali in the described step (5) is sodium hydroxide or potassium hydroxide.
Reductive agent in the described step (7) is a Sodium Nitrite.
Principle of the present invention be with hydroxypropylcellulose in the aqueous solution as template, the acrylic polymers nano-hydrogel of synthesizing biological degradable at first, in alkali and after the acrylic polymers nano-hydrogel contain be negative in a large number-COO
-, attract the Fe be positive in a large number by electrostatic interaction
2+Entering gel network inside, is nano-reactor again with the gel particles, and inner original position is synthesized ferriferrous oxide nano-particle, sees Fig. 1 and Fig. 2.The XRD test has characterized the synthetic magnetic nano-particle and has been Fe
3O
4Crystalline structure; Magnetic force test shows synthetic ferriferrous oxide nano-particle of the present invention has superparamagnetism, and its residual magnetization and coercive force all level off to 0.
Beneficial effect
(1) simple, the environmental protection of this method technology, required equipment be simple and easy to, and can realize producing in batches;
(2) Zhi Bei ferroferric oxide magnetic nano-particles not only has biocompatibility but also have superparamagnetism, and on the acrylic polymers side chain-COOH is active big, helps at the further bonding target of magnetic nano particle sub-surface part; This magnetic nano-particle is applicable to biomedical sectors such as magnetic resonance imaging contrast, target medicine carrier, nano-probe.
Description of drawings
Fig. 1 is for the hydroxypropylcellulose being the synoptic diagram that template does not have the synthetic polyacrylic acid nano hydrogel of saponification;
Fig. 2 is the synthetic and coating Fe of polyacrylic acid nano hydrogel original position
3O
4The synoptic diagram of nanocrystal is represented Fe
3O
4Nanocrystal;
Fig. 3 is the XRD photo of the aquagel evoked original position synthetic of polyacrylic acid nano superparamagnetism ferriferrous oxide nano-particle;
Fig. 4 is the magnetic hysteresis loop figure of the aquagel evoked original position synthetic of polyacrylic acid nano superparamagnetism ferriferrous oxide nano-particle;
Fig. 5 is polyacrylic acid nano hydrogel size and size distribution plot, (a) for coating Fe
3O
4Before; (b) for coating back Fe
3O
4
Embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
The present embodiment step is as follows: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 5g2% (wt%) HPC solution and 0.1gBis are dissolved in the 93g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=6 dialysis 2 days with sodium hydroxide; (6) get 10ml polyacrylic acid nano hydrogel solution and be diluted to 100ml, add 0.6gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 1 day; (7) at N
2Protection adds 0.03gNaNO down
2Powder also stirs 2h, then add 5ml ammoniacal liquor, become black until solution by green, take out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polyacrylic acid nano hydrogel original position coating modification, as shown in Figure 3, its main diffraction peak is respectively 2 θ=30.56 °, 35.820 °, 43.56 °, 53.74 °, 57.219 °, 63.08 °, respectively corresponding cube phase Fe
3O
4(220), (311), (400), (422), (511) and (440) crystal face, with the Fe of standard
3O
4Characteristic diffraction peak match, and XRD spectrum peak is strong high and level and smooth.The XRD test has characterized the synthetic magnetic nano-particle and has been Fe
3O
4Crystalline structure; Magnetic force test shows synthetic ferriferrous oxide nano-particle of the present invention has superparamagnetism, and its residual magnetization and coercive force all level off to 0.
Embodiment 2
The present embodiment step is as follows: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 5g2% (wt%) HPC solution and 0.1gBis are dissolved in the 93g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=7 dialysis 2 days with sodium hydroxide; (6) get 10ml polyacrylic acid nano hydrogel solution and be diluted to 100ml, add 0.6gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 1 day; (7) at N
2Protection adds 0.03gNaNO down
2Powder also stirs 2h, then adds 5ml ammoniacal liquor, becomes black until solution by green, takes out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polyacrylic acid nano hydrogel original position coating modification.
Embodiment 3
The present embodiment step is as follows: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 5g2% (wt%) HPC solution and 0.1gBis are dissolved in the 93g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=6 dialysis 2 days with sodium hydroxide; (6) get 20ml polyacrylic acid nano hydrogel solution and be diluted to 100ml, add 1gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 1 day; (7) at N
2Protection adds 0.03gNaNO down
2Powder also stirs 2h, then adds 5ml ammoniacal liquor, becomes black until solution by green, takes out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polyacrylic acid nano hydrogel original position coating modification.
Embodiment 4
The present embodiment step is as follows: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 5g2% (wt%) HPC solution and 0.1gBis are dissolved in the 93g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=6 dialysis 2 days with sodium hydroxide; (6) get 50ml polyacrylic acid nano hydrogel solution and be diluted to 100ml, add 1.5gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 1 day; (7) at N
2Protection adds 0.03gNaNO down
2Powder also stirs 2h, then adds 5ml ammoniacal liquor, becomes black until solution by green, takes out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polyacrylic acid nano hydrogel original position coating modification.
Embodiment 5
The present embodiment step is as follows: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 5g2% (wt%) HPC solution and 0.1gBis are dissolved in the 93g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=6 dialysis 2 days with sodium hydroxide; (6) get 10ml polyacrylic acid nano hydrogel solution and be diluted to 100ml, add 0.6gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 1 day; (7) at N
2Protection adds 0.06gNaNO down
2Powder also stirs 2h, then adds 5ml ammoniacal liquor, becomes black until solution by green, takes out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polyacrylic acid nano hydrogel original position coating modification.
The present embodiment step is as follows: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 5g2% (wt%) HPC solution and 0.1gBis are dissolved in the 93g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=6 dialysis 2 days with sodium hydroxide; (6) get 10ml polyacrylic acid nano hydrogel solution and be diluted to 100ml, add 0.6gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 1 day; (7) at N
2Protection adds 0.12gNaNO down
2Powder also stirs 2h, then adds 5ml ammoniacal liquor, becomes black until solution by green, takes out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polyacrylic acid nano hydrogel original position coating modification.
Embodiment 7
The present embodiment step is as follows: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 5g2% (wt%) HPC solution and 0.1gBis are dissolved in the 93g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=6 dialysis 2 days with sodium hydroxide; (6) get 10ml polyacrylic acid nano hydrogel solution and be diluted to 100ml, add 0.6gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 1 day; (7) at N
2Protection adds 0.03gNaNO down
2Powder also stirs 2h, then adds 10ml ammoniacal liquor, becomes black until solution by green, takes out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polyacrylic acid nano hydrogel original position coating modification.
Embodiment 8
The present embodiment step is as follows: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 5g2% (wt%) HPC solution and 0.1gBis are dissolved in the 93g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=6 dialysis 2 days with sodium hydroxide; (6) get 10ml polyacrylic acid nano hydrogel solution and be diluted to 100ml, add 0.6gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 1 day; (7) at N
2Protection adds 0.03gNaNO down
2Powder also stirs 2h, then adds 20ml ammoniacal liquor, becomes black until solution by green, takes out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polyacrylic acid nano hydrogel original position coating modification.
Embodiment 9
The present embodiment step is as follows: (1) is with 2g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 98g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 2% (wt%); (2) at ambient temperature, 5g2% (wt%) HPC solution and 0.1gBis are dissolved in the 93g deionized water, stir 15min; (3) add 2g vinylformic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 28 ℃, add the 0.05gTEMED initiated polymerization; (5) the polyacrylic acid nano hydrogel that makes was neutralized to behind the pH=6 dialysis 2 days with sodium hydroxide; (6) get 10ml polyacrylic acid nano hydrogel solution and be diluted to 100ml, add 0.6gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 2 days; (7) at N
2Protection adds 0.03gNaNO down
2Powder also stirs 2h, then adds 20ml ammoniacal liquor, becomes black until solution by green, takes out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polyacrylic acid nano hydrogel original position coating modification.
The present embodiment step is as follows: (1) is with 1g hydroxypropylcellulose (HPC) powder (average M
w=1.0 * 10
5) being dissolved in the 99g deionized water, magnetic agitation 1 day is mixed with the HPC homogeneous phase solution of 1% (wt%); (2) at ambient temperature, 10g1% (wt%) HPC solution and 0.1gBis are dissolved in the 89g deionized water, stir 15min; (3) add 1g methacrylic acid and 0.05gAPS, at N
245min is stirred in protection down; (4) be warming up to 25 ℃, add the 0.05gTEMED initiated polymerization; (5) the polymethyl acrylic acid nano-hydrogel that makes was neutralized to behind the pH=6 dialysis 2 days with sodium hydroxide; (6) get 10ml polymethyl acrylic acid nano-hydrogel solution dilution to 100ml, add 0.6gFeSO
47H
2The O powder is at N
2Protection is stirred the whole night down and was dialysed 1 day; (7) at N
2Protection adds 0.03gNaNO down
2Powder also stirs 2h, then adds 5ml ammoniacal liquor, becomes black until solution by green, takes out dialysis 1 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of polymethyl acrylic acid nano-hydrogel original position coating modification.
Claims (7)
1. the method for an acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle comprises:
(1) under the room temperature hydroxypropylcellulose HPC powder is dissolved in deionized water and magnetic agitation 1～5 day, the homogeneous phase solution that is mixed with 1wt%～10wt% is as standby;
(2) the above-mentioned HPC solution that is mixed with of 5～10g, 0.1g linking agent are dissolved in 87.8～93.8g deionized water and magnetic agitation 15～60min together;
(3) add 0.05g initiator, 1～2g acrylic monomer and stir 15～60min at the nitrogen protection lower magnetic force;
(4) temperature of reaction rises to 20～40 ℃ and add 0.05g accelerator initiated polymerization;
(5) the acrylic polymers nano-hydrogel that makes is transferred to pH=6～8 with alkali, and dialysed 1～3 day;
(6) after 1～10 times of the dilution of the acrylic polymers nano-hydrogel after will dialysing, add 0.6～1.5g FeSO
47H
2The O powder stirs the whole night at the nitrogen protection lower magnetic force, and dialysed 1～3 day;
(7) under nitrogen protection, add 0.03～0.12g reductive agent and stir 2h; add 4.49～20.96g ammoniacal liquor; when solution becomes black by green; stopped reaction; take out dialysis 1～3 day, can obtain the superparamagnetism ferriferrous oxide nano-particle of acrylic polymers nano-hydrogel original position coating modification.
2. the method for a kind of acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle according to claim 1 is characterized in that: the molecular-weight average of the hydroxypropylcellulose in the described step (1) is M
w=1.0 * 10
3～1.0 * 10
6
3. the method for a kind of acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle according to claim 1, it is characterized in that: the linking agent in the described step (2) is N, N '-methylene-bisacrylamide Bis, polyoxyethylene glycol PEG, oxyacetic acid β-ester or (polyethylene glycol-lactic acid-polyoxyethylene glycol) diacrylate.
4. the method for a kind of acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle according to claim 1, it is characterized in that: the initiator in the described step (3) is ammonium persulphate APS or Potassium Persulphate KPS, and acrylic monomer is acrylic or methacrylic acid.
5. the method for a kind of acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle according to claim 1 is characterized in that: the accelerator in the described step (4) is Tetramethyl Ethylene Diamine TEMED or S-WAT.
6. the method for a kind of acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle according to claim 1 is characterized in that: the alkali in the described step (5) is sodium hydroxide or potassium hydroxide.
7. the method for a kind of acrylic polymers nano-hydrogel evoked original position synthesis of super-paramagnetism ferriferrous oxide nano-particle according to claim 1 is characterized in that: the reductive agent in the described step (7) is a Sodium Nitrite.
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| Publication number | Priority date | Publication date | Assignee | Title |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6123681A (en) * | 1998-03-31 | 2000-09-26 | Global Vascular Concepts, Inc. | Anti-embolism stocking device |
| CN101612541A (en) * | 2009-07-17 | 2009-12-30 | 江南大学 | The preparation of polyacrylic acid coated ferroferric oxide magnetic nano-particles and application thereof |
-
2010
- 2010-09-17 CN CN2010102846435A patent/CN101935070B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6123681A (en) * | 1998-03-31 | 2000-09-26 | Global Vascular Concepts, Inc. | Anti-embolism stocking device |
| CN101612541A (en) * | 2009-07-17 | 2009-12-30 | 江南大学 | The preparation of polyacrylic acid coated ferroferric oxide magnetic nano-particles and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 《化工装备技术》 19981231 张平亮 粒子复合化技术及其装置 全文 1-7 第19卷, 第3期 2 * |
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