CN102923782B - Preparation method and biological application of T1-T1 synergistic effect gadolinium chelate manganous-manganic oxide nano particle - Google Patents
Preparation method and biological application of T1-T1 synergistic effect gadolinium chelate manganous-manganic oxide nano particle Download PDFInfo
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- 239000002105 nanoparticle Substances 0.000 title claims abstract description 76
- 229910052688 Gadolinium Inorganic materials 0.000 title claims abstract description 25
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 230000002195 synergetic effect Effects 0.000 title abstract description 4
- GEYXPJBPASPPLI-UHFFFAOYSA-N manganese(III) oxide Inorganic materials O=[Mn]O[Mn]=O GEYXPJBPASPPLI-UHFFFAOYSA-N 0.000 title abstract 6
- 239000013522 chelant Substances 0.000 title abstract 5
- QGLWBTPVKHMVHM-KTKRTIGZSA-N (z)-octadec-9-en-1-amine Chemical compound CCCCCCCC\C=C/CCCCCCCCN QGLWBTPVKHMVHM-KTKRTIGZSA-N 0.000 claims abstract description 14
- HYZQBNDRDQEWAN-LNTINUHCSA-N (z)-4-hydroxypent-3-en-2-one;manganese(3+) Chemical compound [Mn+3].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O HYZQBNDRDQEWAN-LNTINUHCSA-N 0.000 claims abstract description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 9
- 229960003330 pentetic acid Drugs 0.000 claims abstract description 8
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 claims abstract description 5
- AMWRITDGCCNYAT-UHFFFAOYSA-L hydroxy(oxo)manganese;manganese Chemical compound [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 claims description 104
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 239000000463 material Substances 0.000 claims description 13
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 239000002243 precursor Substances 0.000 claims description 11
- 239000001488 sodium phosphate Substances 0.000 claims description 10
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical class [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 9
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 9
- -1 oleyl amines Chemical class 0.000 claims description 9
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 8
- 229960004756 ethanol Drugs 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 238000013019 agitation Methods 0.000 claims description 6
- 239000011259 mixed solution Substances 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 6
- 238000001291 vacuum drying Methods 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- MWFSXYMZCVAQCC-UHFFFAOYSA-N gadolinium(iii) nitrate Chemical class [Gd+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O MWFSXYMZCVAQCC-UHFFFAOYSA-N 0.000 claims description 4
- 239000007983 Tris buffer Substances 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 3
- 239000012153 distilled water Substances 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 238000007789 sealing Methods 0.000 claims description 3
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 claims description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 3
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 229910000474 mercury oxide Inorganic materials 0.000 claims description 2
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 235000011008 sodium phosphates Nutrition 0.000 claims 2
- 230000000694 effects Effects 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 7
- 239000003446 ligand Substances 0.000 abstract description 5
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052748 manganese Inorganic materials 0.000 abstract description 3
- 239000011572 manganese Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 125000003277 amino group Chemical group 0.000 abstract 2
- 238000002595 magnetic resonance imaging Methods 0.000 abstract 2
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 abstract 1
- 229940062527 alendronate Drugs 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 238000000197 pyrolysis Methods 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- 239000002872 contrast media Substances 0.000 description 17
- 238000003384 imaging method Methods 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- CTYVBSGIFONFHX-UHFFFAOYSA-N [Mn].[Gd] Chemical compound [Mn].[Gd] CTYVBSGIFONFHX-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
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- 230000005540 biological transmission Effects 0.000 description 2
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- 239000002244 precipitate Substances 0.000 description 2
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- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Abstract
The invention discloses a preparation method and biological application of T1-T1 synergistic effect gadolinium chelate manganous-manganic oxide nano particles. The preparation method and the biological application of the T1-T1 synergistic effect gadolinium chelate manganous-manganic oxide nano particles include that firstly manganeseacetylacetonate is combined, and then oleylamine is used as a solvent, a high-temperature pyrolysis method is used to combine oil solubility manganous-manganic oxide nano particles, and then a ligand exchange method is utilized to use alendronate to be exchanged on the surfaces of the manganous-manganic oxide nano particles, so that nano particles are formed, wherein the surfaces of the nano particles are provided with a large number of amino groups. Then, the surfaces of the amino groups are connected with diethylenetriamine pentaacetic acid, so that the surfaces of the nano particles are provided with a large number of carboxyl groups, and at last a chelate effect is utilized to enable the large number of carboxyl groups and gadolinium to be chelated. Therefore, gadolinium chelate manganous-manganic oxide nano particles are obtained. The preparation method is low in requirement for equipment, convenient for operated process, low in needed raw material cost, and nuisanceless in accessory products. And at last through in vitro and in vivo magnetic resonance imaging experimental testing, so that compared with independent manganese and independent gadolinium, T1 magnetic resonance imaging contrast effect is strengthened.
Description
Technical field
The invention belongs to contrast agent technical field, relate to a kind of preparation method and biologic applications thereof of enhancement mode imaging contrast agent, specifically a kind of T
1-T
1preparation method and the biologic applications thereof of synergism gadolinium chelating trimanganese tetroxide nano particle.
Background technology
From CT is born, medical imaging has been passed by high-speed development period of 40 years.Today, we have had the very powerful image documentation equipment of performance: 320 layers of CT, and 7T magnetic resonance, PET-CT, a kind of display capabilities limit of image documentation equipment is determined by its principle.CT is to add that with x-ray rotating acquisition carrys out imaging.The time of imaging is in submicrosecond level.In rotary course, slip ring certainly leads to shake, and x-ray intensity is not being stopped fluctuation, and blood of human body and organ are in motion, and these have all determined that its spatial resolution can only be confined to submillimeter level, may show never body of gland level and cell grade anatomical structure.Last clinical practice of CT: arteria coronaria shows to be realized, and there will be no what quantum jump future.The principle of magnetic resonance is molecular specificity contrast, but due to signal to noise ratio restriction, only has same molecule to reach some and just can develop.Another display capabilities of magnetic resonance is the motion of microcosmic, comprises the motion of blood and the disperse campaign of water, but molecule that equally need to be based on abundant.Thereby magnetic resonance can not show the structure of body of gland level and cell grade.Mention PET, leading role herein starts to have come on stage---contrast agent.If there is no contrast agent, PET can not form any image.
Contrast agent is a kind of outer material that adds to human body, by certain mechanism, changes image information, increases diagnostic imaging information.When contrast agent is undeveloped, we can only show more anatomical detail by improving constantly the performance of image documentation equipment, and then improve the ability of discovery of pathological changes.This has not only significantly improved check cost, and that has also significantly improved doctor reads sheet workload.And after having had contrast agent, we only need the most basic image documentation equipment imaging performance, as long as can show contrast agent, because contrast agent where, pathological changes is with regard to where.When we can develop multiple pathological changes specific contrast agent, can easily obtain diagnosis.
So want to promote the development of future medicine, must work out more flourishing contrast agent, this is extremely urgent.
People have been deep into more and more less range scale to the research of nano material, and increasing functional character.The aspects such as nano-contrast agent Ultrahigh-Density Data Storage, biomolecule identification, medicine transmission have extremely important application, become the great research topic of International Technology circle.The field such as biochemistry and medical science has strict requirement to the physics of nano-contrast agent, chemistry and pharmacological properties as chemical composition, granule size, magnetic function, crystal structure, surface topography, dissolubility and toxicity etc.Realize the nano-contrast agent of better effect in the application in the fields such as biochemistry and medical science, must meet the following conditions: 1. hypotoxicity; 3. there is water solublity; 4. there is good monodispersity; 5 have good or in-vivo imaging effect.
The present invention becomes water miscible nanoparticle by ligand exchange, then at particle surface, connects a large amount of carboxyls, then by gadolinium on the chelation chelating of carboxyl.Make nanoparticle there is the stronger imaging effect of manganese gadolinium combination, there is good dispersibility and water solublity simultaneously.Synthetic method of the present invention is simple, the advantages such as reaction condition is gentle, required raw material is easy to get, cheap, operating process convenience, non-environmental-pollution.Have and the gadolinium that uses simple reaction unit can prepare uniform particle diameter, good dispersion, good water solubility has synergistic trimanganese tetroxide nano particle.
Through extensively retrieving domestic and international patent document and public publication, be showed no the nanoparticle research method with cooperative effect identical with the present invention.The present invention has novelty, creativeness, practicality.
Summary of the invention
The object of this invention is to provide a kind of imaging effect good, there is good dispersion and water solublity, simultaneously the simple contrast agent of synthetic method, i.e. T
1-T
1preparation and the biologic applications thereof of synergism gadolinium chelating trimanganese tetroxide nano particle.
The object of the present invention is achieved like this:
A preparation method for T1-T1 synergism gadolinium chelating trimanganese tetroxide nano particle, comprises the steps:
(1) by MnCl
24H
2o is soluble in water, adds acetylacetone,2,4-pentanedione, under room temperature, stirs 30-40min; Add again triethylamine, filter to obtain precipitate; Precipitate is joined in the mixed solution of ethanol and water, be heated to 75-80 ℃, be stirred to completely and dissolve; Room temperature is cooling, filters, and obtains manganese acetylacetonate precursor;
(2) manganese acetylacetonate precursor making is dissolved in oleyl amine, magnetic agitation in nitrogen atmosphere, is slowly heated to 140-145 ℃, and isothermal reaction 5-6h is cooled to centrifugalize after room temperature; Material after separation is washed 3-5 time continuously with dehydrated alcohol, makes the brown material oil-soluble trimanganese tetroxide nano particle of surperficial oleyl amine coordination;
(3) nanoparticle making in step (2) is dissolved in oleyl amine, ultrasonic; Add manganese acetylacetonate precursor, magnetic agitation in nitrogen atmosphere, is slowly heated to 220-230 ℃, isothermal reaction 10-12h; Be cooled to centrifugalize after room temperature; Material after separation is washed 3-5 time continuously with dehydrated alcohol; Vacuum drying; Make the brown material oil-soluble trimanganese tetroxide nano particle of surperficial oleyl amine coordination;
(4) in Allan sodium phosphate, add distilled water, then add TBAH that Allan sodium phosphate is all dissolved; Trimanganese tetroxide nano particle in step (3) is dissolved in dehydrated alcohol, adds in the solution of above-mentioned Allan sodium phosphate stirring reaction 9-10h, centrifugalize; After separated, use absolute ethanol washing 3-5 time, vacuum drying, makes surface with a large amount of amino water solublity trimanganese tetroxide nano particles;
(5) get that step (4) makes water solublity trimanganese tetroxide nano particle and diethyl pentetic acid (DTPA) is dissolved in respectively anhydrous N, N dimethylformamide (DMF) stirs 10-12h in nitrogen atmosphere after mixing; Centrifugalize, respectively washs 2-3 time with second alcohol and water respectively, makes the water solublity trimanganese tetroxide nano particle that there are a large amount of carboxyls on surface;
(6) Gadolinium trinitrate is dissolved in Tris solution, adds step (5) to prepare water solublity trimanganese tetroxide nano particle, sealing evacuation, stirring at room 9-10h under nitrogen protection; Centrifugalize, uses absolute ethanol washing 5-7 time, makes the trimanganese tetroxide nano particle of gadolinium chelating.
In the mixed solution of the middle ethanol of step (1) and water, the volume ratio of ethanol and water is 3-5:1, preferably 4:1.
Trimanganese tetroxide nano particle in step (4) and the mass ratio of Allan sodium phosphate are 1:35-45, preferably 1:40.
Water solublity trimanganese tetroxide nano particle in step (5) and the mass ratio of diethyl pentetic acid are 4-6:2, preferably 5:2.
Water solublity trimanganese tetroxide nano particle in step (6) and the mass ratio of Gadolinium trinitrate are 4-6:2, preferably 5:2.
First the present invention is prepared oil-soluble magnetic nano-particle by the method for thermal decomposition, then by ligand exchange, make nanoparticle change water solublity into, and surface is with a large amount of amino, then connect diethyl pentetic acid (DTPA) and make nanoparticle surface have a large amount of carboxyls, finally by chelation, connect gadolinium.Thereby the chelating of realizing synthetic manganese and gadolinium, forms the coefficient nanoparticle contrast agent of manganese gadolinium.
Advantage of the present invention is:
1. the nanoparticle good stability of the manganese gadolinium chelating making;
The particle diameter of preparation evenly, good dispersion, good water solubility;
Raw material be easy to get, cheap;
4. couple T
1imaging has the effect of enhancing;
5. couple T
1the research of contrast agent has the contribution of inquiry.
Accompanying drawing explanation
Fig. 1 is the X diffracting spectrum of the oil-soluble trimanganese tetroxide nano particle that synthesizes.
Fig. 2 is that synthetic surface organic ligands is the transmission electron microscope collection of illustrative plates (TEM figure) of the trimanganese tetroxide nano particle of oleyl amine, and Fig. 2 shows that trimanganese tetroxide nano particle has good monodispersity in cyclohexane extraction, and particle diameter is 11 nanometer left and right.
Fig. 3 is the T of trimanganese tetroxide nano particle in aqueous solution that has a large amount of amino with Allan sodium phosphate ligand exchange rear surface
1nMR (Nuclear Magnetic Resonance)-imaging figure, shows that this nanoparticle has good T
1imaging effect.
Fig. 4 is that synthetic surface of the present invention is with T in the aqueous solution of the trimanganese tetroxide nano particle of a large amount of carboxyls
1nMR (Nuclear Magnetic Resonance)-imaging figure, imaging effect is better with contrasting above, r
1be worth larger.
Fig. 5 is the compound T of commercial diethyl pentetic acid chelating gadolinium
1nMR (Nuclear Magnetic Resonance)-imaging figure.
Fig. 6 is that chelating connects trimanganese tetroxide nano particle after the gadolinium T in aqueous solution
1nMR (Nuclear Magnetic Resonance)-imaging figure, the trimanganese tetroxide nano particle after chelating gadolinium is at T as can be seen from this figure
1in imaging effect, than independent manganese and independent gadolinium, there is obvious advantage.
Fig. 7 is trimanganese tetroxide nano particle after the synthetic Allan sodium phosphate ligand exchange T in HeLa cell
1nMR (Nuclear Magnetic Resonance)-imaging figure, nanoparticle concentration is respectively every milliliter of 1,10,20,50,100 microgram.
Fig. 8 is that above-mentioned nanoparticle surface connects trimanganese tetroxide nano particle after the diethyl pentetic acid T in HeLa cell
1nMR (Nuclear Magnetic Resonance)-imaging figure, nanoparticle concentration is respectively every milliliter of 1,10,20,50,100 microgram.
Fig. 9 is the trimanganese tetroxide nano particle T in HeLa cell after chelating gadolinium
1nMR (Nuclear Magnetic Resonance)-imaging figure, nanoparticle concentration is respectively every milliliter of 1,10,20,50,100 microgram.
The specific embodiment
Preparation method with the trimanganese tetroxide nano particle of manganese gadolinium chelating, comprises the steps:
(1) prepare manganese acetylacetonate precursor:
Get 2.5 grams of MnCl
24H
2o is dissolved in 15mL water; In above-mentioned solution, add 5.0mL acetylacetone,2,4-pentanedione; Under room temperature, stir 30min; Add 5.0mL triethylamine; Yellow mercury oxide in abstraction reaction liquid also filters;
Dose volume, than being the ethanol of 4:1 and water mixed solution, being filtered by extraction the yellow solid obtaining and is added in ethanol, water mixed solution, is heated to 75-80 ℃, is stirred to completely and dissolves and make solution be brown transparency liquid; Room temperature is cooling, and in filtering solution, yellow acicular crystal, obtains manganese acetylacetonate precursor;
(2) prepare surperficial oleyl amine coordination oil-soluble trimanganese tetroxide nano particle seed:
Get 0.4 gram of manganese acetylacetonate precursor that above-mentioned steps makes and be dissolved in 9.5 grams of oleyl amines, evacuation, magnetic agitation in nitrogen atmosphere, is slowly heated to 140 ℃, isothermal reaction 5h; Be cooled to centrifugalize after room temperature; Material after separation is washed 3 times continuously with dehydrated alcohol; Make the brown material oil-soluble trimanganese tetroxide nano particle of surperficial oleyl amine coordination;
(3) seed law is prepared the trimanganese tetroxide nano particle that particle diameter is larger:
The nanoparticle making in step (2) is dissolved in the oleyl amine of 16g, ultrasonic; Add 0.6g manganese acetylacetonate precursor, evacuation, magnetic agitation in nitrogen atmosphere, is slowly heated to 220 ℃, isothermal reaction 10h; Be cooled to centrifugalize after room temperature; Material after separation is washed 3 times continuously with dehydrated alcohol; Vacuum drying; Make the brown material oil-soluble trimanganese tetroxide nano particle of surperficial oleyl amine coordination;
(4) prepare water miscible trimanganese tetroxide nano particle:
Trimanganese tetroxide nano particle in step (3) is got in the dehydrated alcohol that 30mg is dissolved in 2mL; Get 1.2g Allan sodium phosphate; Add 20mL distilled water; Add again TBAH that Allan sodium phosphate is all dissolved; Then slowly add trimanganese tetroxide nano particle; Stirring reaction 9h; Centrifugalize; After separated, use absolute ethanol washing 3 times; Vacuum drying; Make surface with a large amount of amino water solublity trimanganese tetroxide nano particles;
(5) get step (4) and make water soluble nanometer particles 20mg and be dissolved in anhydrous N, N dimethylformamide (DMF), takes diethyl pentetic acid (DTPA) 7.9mg and is dissolved in 8mLDMF, both solution ultrasonic dissolutions are even, insert in container, evacuation stirs 10h in nitrogen atmosphere; Centrifugalize, respectively washs 2 times with second alcohol and water respectively, makes the water solublity trimanganese tetroxide nano particle that there are a large amount of carboxyls on surface;
(6) prepare the trimanganese tetroxide nano particle of gadolinium chelating:
Get step (5) and prepare water solublity trimanganese tetroxide nano particle 20mg; Get 10mL Tris solution dissolving 8mg Gadolinium trinitrate and insert in container, sealing evacuation, nitrogen protection; Stirring at room 9h; Centrifugalize, uses absolute ethanol washing 5 times, makes the trimanganese tetroxide nano particle of gadolinium chelating.
The above is preferred embodiment of the present invention, but the present invention should not be confined to the disclosed content of this embodiment.So every, do not depart from the equivalence completing under spirit disclosed in this invention or revise, all falling into the scope of protection of the invention.
Claims (1)
1. a T
1-T
1the preparation method of synergism gadolinium chelating trimanganese tetroxide nano particle, is characterized in that, comprises the steps:
(1) prepare manganese acetylacetonate precursor:
Get 2.5 grams of MnCl
24H
2o is dissolved in 15mL water; In above-mentioned solution, add 5.0mL acetylacetone,2,4-pentanedione; Under room temperature, stir 30min; Add 5.0mL triethylamine; Yellow mercury oxide in abstraction reaction liquid also filters;
Dose volume, than being the ethanol of 4:1 and water mixed solution, being filtered by extraction the yellow solid obtaining and is added in ethanol, water mixed solution, is heated to 75-80 ℃, is stirred to completely and dissolves and make solution be brown transparency liquid; Room temperature is cooling, and in filtering solution, yellow acicular crystal, obtains manganese acetylacetonate precursor;
(2) prepare surperficial oleyl amine coordination oil-soluble trimanganese tetroxide nano particle seed:
Get 0.4 gram of manganese acetylacetonate precursor that above-mentioned steps makes and be dissolved in 9.5 grams of oleyl amines, evacuation, magnetic agitation in nitrogen atmosphere, is slowly heated to 140 ℃, isothermal reaction 5h; Be cooled to centrifugalize after room temperature; Material after separation is washed 3 times continuously with dehydrated alcohol; Make the brown material oil-soluble trimanganese tetroxide nano particle of surperficial oleyl amine coordination;
(3) seed law is prepared the trimanganese tetroxide nano particle that particle diameter is larger:
The nanoparticle making in step (2) is dissolved in the oleyl amine of 16 g, ultrasonic; Add 0.6 g manganese acetylacetonate precursor, evacuation, magnetic agitation in nitrogen atmosphere, is slowly heated to 220 ℃, isothermal reaction 10 h; Be cooled to centrifugalize after room temperature; Material after separation is washed 3 times continuously with dehydrated alcohol; Vacuum drying; Make the brown material oil-soluble trimanganese tetroxide nano particle of surperficial oleyl amine coordination;
(4) prepare water miscible trimanganese tetroxide nano particle:
Trimanganese tetroxide nano particle in step (3) is got in the dehydrated alcohol that 30 mg are dissolved in 2 mL; Get 1.2 g Allan sodium phosphates; Add 20 mL distilled water; Add again TBAH that Allan sodium phosphate is all dissolved; Then slowly add trimanganese tetroxide nano particle; Stirring reaction 9 h; Centrifugalize; After separated, use absolute ethanol washing 3 times; Vacuum drying; Make surface with a large amount of amino water solublity trimanganese tetroxide nano particles;
(5) getting step (4) makes water soluble nanometer particles 20 mg and is dissolved in anhydrous N, dinethylformamide (DMF), taking diethyl pentetic acid (DTPA) 7.9 mg is dissolved in 8 mLDMF, both solution ultrasonic dissolutions are even, insert in container, evacuation stirs 10 h in nitrogen atmosphere; Centrifugalize, respectively washs 2 times with second alcohol and water respectively, makes the water solublity trimanganese tetroxide nano particle that there are a large amount of carboxyls on surface;
(6) prepare the trimanganese tetroxide nano particle of gadolinium chelating:
Get step (5) and prepare water solublity trimanganese tetroxide nano particle 20 mg; Get 10 mL Tris solution and dissolve 8 mg Gadolinium trinitrates and insert in container, sealing evacuation, nitrogen protection; Stirring at room 9 h; Centrifugalize, uses absolute ethanol washing 5 times, makes the trimanganese tetroxide nano particle of gadolinium chelating.
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| CN102320664A (en) * | 2011-09-30 | 2012-01-18 | 上海师范大学 | Preparation method for amino-functionalized water-soluble magnetic manganomanganic oxide nanoparticles |
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| CN102320664A (en) * | 2011-09-30 | 2012-01-18 | 上海师范大学 | Preparation method for amino-functionalized water-soluble magnetic manganomanganic oxide nanoparticles |
Non-Patent Citations (2)
| Title |
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| 庄业明.纳米多功能磁共振造影剂的设计、合成及其生物应用.《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》.2011,(第11期),第5-6页及第51-53页. |
| 纳米多功能磁共振造影剂的设计、合成及其生物应用;庄业明;《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》;20111115(第11期);第5-6页及第51-53页 * |
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