CN106139167A - Six cyanogen metal complex nanoparticle and mri contrast agents thereof of manganese - Google Patents
Six cyanogen metal complex nanoparticle and mri contrast agents thereof of manganese Download PDFInfo
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Abstract
The present invention relates to a kind of molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanoparticle and mri contrast agent purposes thereof of the manganese of n=0,1-20, six cyanogen metal complex nanoparticles of this manganese can serve as T2 mri contrast agent crude drug.
Description
Technical field
The present invention relates to a kind of molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；
M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanometers of the manganese of n=0,1-20
Particle and mri contrast agent purposes thereof, it is former that six cyanogen metal complex nanoparticles of this manganese can serve as mri contrast agent
Material medicine.
Background technology
The present invention relates to a kind of molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；
M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanometers of the manganese of n=0,1-20
Particle and mri contrast agent purposes thereof, it is former that six cyanogen metal complex nanoparticles of this manganese can serve as mri contrast agent
Material medicine.
Summary of the invention
The present invention relates to a kind of molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；
M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanometers of the manganese of n=0,1-20
Particle and mri contrast agent purposes thereof, it is former that six cyanogen metal complex nanoparticles of this manganese can serve as mri contrast agent
Material medicine.
1, molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn,
Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And the preparation of n=0,1-20 compound crystal, mainly comprise the steps that
With six cyanogen metal complex ion [M (CN)6]n-(M=Cr, Mn, Fe, Co or Ru, n=3-4) and divalent manganesetion Mn2+
By hybrid reaction, obtaining molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；
M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And the crystallization of n=0,1-20 compound.
Wherein six cyanogen metal complex ion [M (CN)6]n-(M=Cr, Mn, Fe, Co or Ru, n=3-4), is dissolved in 0.1%-20%
The aqueous citric acid solution of (weight) is referred to as A1, is dissolved in 0.1%-20% (weight) aqueous tartaric acid solution referred to as A2, molten
Solution is in lactic acid: be referred to as A3 in the lactic acid aqueous solution of the volume ratio 1: 1-20 of water；
Wherein divalent manganesetion Mn2+, it is dissolved in the aqueous citric acid solution of 0.1%-20% (weight) referred to as B1, is dissolved in
0.1%-20% (weight) aqueous tartaric acid solution is referred to as B2, is dissolved in lactic acid: the lactic acid aqueous solution of the volume ratio 1: 1-20 of water
In be referred to as B3；
A 1 is poured in B 1 to obtain C 1, or A 1 is poured in B 2 to obtain C 2, or A 1 is poured in B 3 to obtain C 3；
A 2 is poured in B 1 to obtain D 1, or A 2 is poured in B 2 to obtain D 2, or A 2 is poured in B 3 to obtain D 3；
A 3 is poured in B 1 to obtain E 1, or A 3 is poured in B 2 to obtain E 1, or A 3 is poured in B 3 to obtain E 3.
Above-mentioned hybrid mode obtains C I, C 2, C 3, D 1, D 2, D 3, E 1, E 2, E 3 crystallize, its
Molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn, Fe, Co
Or Ru；X=0-2；Y=1-4；Z=1-4；And n=0,1-20, crystalline particle particle diameter between 0.2-120 micron, one of which
The x-ray diffractogram of powder of crystallization is shown in Fig. 1, and the x-ray diffractogram of powder of another all crystallization is shown in Fig. 2, but be not limited to this two
Plant crystallization and x-ray diffractogram of powder thereof.
2, molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn,
Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And the preparation of six cyanogen metal complex nanoparticles of the manganese of n=0,1-20
Mainly comprise the steps that
It is AxMny [M (CN) by molecular formula6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn,
Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；With n=0,1-20 compound crystal corrosion is mannitol, Portugal's first at formula
Amine, polyvinylpyrrolidone, nicotinic acid, disodium edetate, cysteine aqueous solution in；Or corrosion formula be mannitol,
Meglumine, polyvinylpyrrolidone, nicotinic acid, disodium edetate aqueous solution in；Or corrosion formula be mannitol, meglumine,
Polyvinylpyrrolidone, nicotinic acid, cysteine aqueous solution in；Or corrosion is mannitol, meglumine, polyethylene pyrrole at formula
Pyrrolidone, disodium edetate, cysteine aqueous solution in；Or corrosion is mannitol, meglumine, polyvinyl pyrrole at formula
In alkanone, cigarette aqueous acid；Or corrosion is mannitol, meglumine, polyvinylpyrrolidone, disodium edetate at formula
In aqueous solution；Or corrosion is in the aqueous solution that formula is mannitol, meglumine, polyvinylpyrrolidone, cysteine；Or it is molten
Erosion is in the aqueous solution that formula is mannitol, meglumine, polyvinylpyrrolidone；Or corrosion formula be mannitol, meglumine,
Nicotinic acid, disodium edetate, cysteine aqueous solution in, stir to solution transparent after, add polyvinylpyrrolidone follow-up
Continuous stirring is transparent to solution；Or corrosion formula be mannitol, meglumine, nicotinic acid, disodium edetate, aqueous solution in, stir
Mix to solution transparent after, add that to continue stirring after polyvinylpyrrolidone transparent to solution；Or corrosion formula be mannitol,
Meglumine, nicotinic acid, cysteine aqueous solution in, stir to solution transparent after, continue to stir after adding polyvinylpyrrolidone
Mix to solution transparent；Or corrosion is in the aqueous solution that formula is mannitol, meglumine, disodium edetate, cysteine, stirring
To solution transparent after, add that to continue stirring after polyvinylpyrrolidone transparent to solution；Or corrosion is mannitol, Portugal at formula
In methylamine, cigarette aqueous acid, after stirring to solution is transparent, continue stirring after adding polyvinylpyrrolidone transparent to solution；
Or corrosion is in the aqueous solution that formula is mannitol, meglumine, disodium edetate, after stirring to solution is transparent, add poly-second
Stirring is continued transparent to solution after alkene pyrrolidone；Or corrosion is in the aqueous solution that formula is mannitol, meglumine, cysteine,
Stir to solution transparent after, add that to continue stirring after polyvinylpyrrolidone transparent to solution；In said process, polyethylene pyrrole
Pyrrolidone can substitute with chitosan, or available dextran substitutes, or available carboxyl dextran substitutes, or available glucosan replaces
Generation, or available Sensor Chip CM 5 substitute, or available Polyethylene Glycol substitute, each Ingredient Amount be mannitol be 2-20% (weight),
Meglumine is 2%-20% (weight), and nicotinic acid is 0.01-5.0% (weight), and disodium edetate is 0.01-5.0% (weight), half
Cystine is 0.01%-5.0% (weight), and polyvinylpyrrolidone is 2%-20% (weight), and chitosan is 1.0%-15% (weight
Amount), dextran is 1.0%-15% (weight), and carboxyl dextran is 1.0%-15% (weight), and glucosan is 1.0%-15%
(weight), Sensor Chip CM 5 is 1.0%-15% (weight), and Polyethylene Glycol is 1.0%-20% (weight), in said process,
Each composition all dissolves or continues stirring 0.5-36 hour after corrosion, and the molecular formula forming stable transparent is
AxMny[M(CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn, Fe, Co or Ru；
X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanoparticle and nano-particle solution thereof of the manganese of n=0,1-20, its
Middle nanoparticle PH between 3.5-12.6 stable, Nanoparticle Size between 0.1nm-200nm, nano-particle solution
Divalent manganesetion content is between 0.1-400mM.
3, molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn,
Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nano-particle solution of the manganese of n=0,1-20,
Its nuclear magnetic resonance, NMR magnetic Henan rate test result is r1=2-80.Nano-particle solution magnetic Henan rate r1=3.7169 of one of which crystallization, is shown in
Fig. 4；Nuclear magnetic resonance, NMR T1 weighted imaging imaging results, is shown in Fig. 5.
4, molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn,
Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanoparticle contrast agents of the manganese of n=0,1-20
Preparation mainly comprise the steps that
By prepared molecular formula be molecular formula be AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；
M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；With six cyanogen metal complexs of the manganese of n=0,1-20 receive
Rice corpuscles solution is configured to the concentration containing manganese 2-50mM, through 0.22 μm microporous filter membrane aseptic filtration, aseptic subpackaged to cillin bottle
In, i.e. prepare six cyanogen metal complex nano-NMR contrast agent of liquid manganese, can use by injection for intravenous；
By prepared molecular formula be molecular formula be AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；
M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；With six cyanogen metal complexs of the manganese of n=0,1-20 receive
Rice corpuscles solution is configured to the concentration containing manganese 2-50mM, and through 0.22 μm microporous filter membrane aseptic filtration, gained filtrate presses aseptic spray
Mist lyophilisation or vacuum freeze-drying method process, and obtain dry powder, aseptic subpackaged in cillin bottle, i.e. prepare solid-state manganese
Six cyanogen metal complex nano-NMR contrast agent, use front water for injection or injection normal saline dilution, be made into and contain
The concentration of manganese 2-50mM, can use by injection for intravenous.
5, molecular formula be molecular formula be AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr,
Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanoparticle cores of the manganese of n=0,1-20
Magnetic resonance contrast agent test result indicate that for rat liver magnetic resonance imaging:
T2 contrastographic picture is obviously reduced, and signal enhancement value, than blank signal value relative reduction more than 65%, is shown in Fig. 9, Figure 10, figure
11, Figure 12；Rat after radiography experiment is raised 2 weeks, its outward appearance of period and behavior no abnormality seen.
Accompanying drawing explanation
Fig. 1 be the molecular formula prepared by the embodiment of the present invention 1 be AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K,
NH4, or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=14；And n=0,1-20 compound crystal
Middle molecule formula is Mn3[Fe(CN)6]2(H2O)m, the wherein Powder x-ray diffraction figure of the compound crystal of n=0-13.
Fig. 2 be the molecular formula prepared by the embodiment of the present invention 2 be AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K,
NH4, or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen of the manganese of n=0,1-20
Metal complex nano-particle solution Middle molecule formula is Mn3[Fe(CN)6]2(H2O)m, wherein six cyanogen metal complexes of the manganese of n=0-13
Thing nano-particle solution transmission electron microscope picture, nano particle diameter is between 1-10nm.
Fig. 3 be the molecular formula prepared by the embodiment of the present invention 2 be AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K,
NH4, or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen of the manganese of n=0,1-20
Metal complex nano-particle solution Middle molecule formula is Mn3[Fe(CN)6]2(H2O)n, wherein six cyanogen metal complexes of the manganese of n=0-13
Thing nano-particle solution transmission electron microscope elementary analysis energy spectrogram, the ratio recording manganese and ferrum is 1.5: 1.
Fig. 4 be the embodiment of the present invention 4 Middle molecule formula be AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4,
Or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal networks of the manganese of n=0,1-20
Compound nano-particle solution Middle molecule formula is Mn3[Fe(CN)6]2(H2O)n, wherein n=0-13 six cyanogen metal complexs of manganese receive
Rice corpuscles solution nuclear magnetic resonance relaxation rate r1 test result, magnetic Henan rate r1=3.7169.
Fig. 5 be the embodiment of the present invention 4 Middle molecule formula be AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4,
Or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal networks of the manganese of n=0,1-20
Compound nano-particle solution Middle molecule formula is Mn3[Fe(CN)6]2(H2O)n, wherein six cyanogen metal complex nanometers of the manganese of n=0-13
Particle solution nuclear magnetic resonance, NMR T1 weighted imaging result.
Fig. 6 is the molecular formula AxMny [M (CN) prepared by the embodiment of the present invention 56]z·(H2O) n, wherein A=Li, Na, K,
NH4, or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen of the manganese of n=0,1-20
Metal complex crystallization Middle molecule formula is KMn [Fe (CN)6](H2O)n, the wherein powder of six cyanogen metal complex crystallizations of the manganese of n=0-4
End x-ray diffraction pattern.
Fig. 7 is the molecular formula AxMny [M (CN) prepared by the embodiment of the present invention 66]z·(H2O) n, wherein A=Li, Na, K, NH4,
Or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal networks of the manganese of n=0,1-20
Compound nano-particle solution Middle molecule formula is KMn [Fe (CN)6](H2O)n, wherein six cyanogen metal complex nanoparticles of the manganese of n=0-4
Sub-solution, through the nanoparticle that transmission electron microscope observing arrives, nano particle diameter is between 40-70nm.
Fig. 8 is the molecular formula AxMny [M (CN) prepared by the embodiment of the present invention 66]z·(H2O) n, wherein A=Li, Na, K, NH4,
Or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal networks of the manganese of n=0,1-20
Compound nano-particle solution Middle molecule formula is KMn [Fe (CN)6](H2O)n, wherein six cyanogen metal complex nanoparticles of the manganese of n=0-4
Sub-solution transmission electron microscope elementary analysis energy spectrogram, records potassium: manganese: the ratio of ferrum is 1: 1: 1.
Fig. 9 is in the embodiment of the present invention 8, by the dosage of 1ml/300g by tail vein injection to before in rat body, does core
Magnetic resonance radiography, obtains magnetic resonance imaging T2 image and the signal value of the rat liver before injection.
Figure 10 is in the embodiment of the present invention 8, by the dosage of 1ml/300g by tail vein injection to rat body, does nuclear-magnetism altogether
Shake radiography, the magnetic resonance imaging T2 image of rat liver and signal value when must inject latter 20 minutes.
Figure 11 is in the embodiment of the present invention 9, by the dosage of 1ml/300g by tail vein injection to before in rat body, does core
Magnetic resonance radiography, obtains magnetic resonance imaging T2 image and the signal value of the rat liver before injection.
Figure 12 is in the embodiment of the present invention 9, by the dosage of 1ml/300g by tail vein injection to rat body, does nuclear-magnetism altogether
Shake radiography, the magnetic resonance imaging T2 image of rat liver and signal value when must inject latter 20 minutes.
Detailed description of the invention
Embodiment 1:
Molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=K；M=Fe；X=0-2；Y=1-4；Z=1-4；And n=0,
Six cyanogen metal complex crystallization Middle molecule formulas of 1-20 manganese are Mn3[Fe(CN)6]2(H2O)n, the wherein Manganese hexacyanoferrate crystallization of n=0-13
Preparation
Weigh 843 milligrams of K3[Fe(CN)6] put in 100 milliliters of beakers, add 10% aqueous citric acid solution 25ml and be completely dissolved,
It is called for short sample A；Weigh 495 milligrams of MnCl2·4H2O puts in 100 milliliters of flasks, addition lactic acid: the volume ratio 1: 10 of water
Lactic acid aqueous solution 25ml be completely dissolved, be called for short sample B；Sheng A sample is poured in the beaker of B sample, seal beaker with sealing compound
Mouthful, under lucifuge, room temperature obtains molecular formula after standing 12 hours is AxMny [M (CN)6]z·(H2O) n, wherein A=K；M=Fe；
X=0-2；Y=1-4；Z=1-4；With six cyanogen metal complex crystallization Middle molecule formulas of the manganese of n=0,1-20 are
Mn3[Fe(CN)6]2(H2O)n, the wherein compound crystal of n=0-13, its x-ray diffractogram of powder is shown in Fig. 1.
Embodiment 2:
Molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=K；M=Fe；X=0-2；Y=1-4；Z=1-4；And n=0,
Six cyanogen metal complex nanoparticle Middle molecule formulas of the manganese of 1-20 are Mn3[Fe(CN)6]2(H2O)n, wherein the six of the manganese of n=0-13
The preparation of cyanogen metal complex nanoparticle
Weigh 6.00g mannitol, meglumine 10.00g, nicotinic acid 1.33g, disodium edetate 1.29g, cysteine 0.31g in
In 100ml beaker, add water to 70ml, magnetic agitation, to being completely dissolved, be called for short sample A.
Weigh polyvinylpyrrolidone 10g again to add in sample A by several times, be stirred continuously, and be progressively heated to 60 DEG C, maintain 60 DEG C
Being completely dissolved to polyvinylpyrrolidone, solution is that micro-Huang is transparent, is then cooled to room temperature, is called for short sample B.
Weighing molecular formula is Mn3[Fe(CN)6]2(H2O)n, wherein the compound Manganese hexacyanoferrate crystallization 0.224g of n=0-13 joins
In sample B, being stirred continuously, to the complete corrosion of this crystallization, solution is amber transparent, continues stirring 12 hours, and obtaining molecular formula is
Mn3[Fe(CN)6]2(H2O)n, wherein six cyanogen metal complex nano-particle solution of the manganese of n=0-13, are called for short sample C.Record sample
The pH value of C is 11.0；Transmission electron microscope observation to sample C nano particle equiblibrium mass distribution in the solution, particle diameter at 1-10nm,
See Fig. 2；It is 1.5: 1 that transmission electron microscope elementary analysis power spectrum records the ratio of sample C manganese and ferrum, sees Fig. 3；
Embodiment 3:
It is Mn by molecular formula prepared in embodiment 23[Fe(CN)6]2(H2O)n, wherein six cyanogen metal complexes of the manganese of n=0-13
Thing nano-particle solution sample C is configured to the concentration containing manganese 10mM, through 0.22 μm microporous filter membrane aseptic filtration, aseptic subpackaged
In cillin bottle, i.e. prepare six cyanogen metal complex nano-NMR contrast agent of the manganese of liquid, be called for short sample D, be available for vein
Injection uses；
Embodiment 4:
Sample C relaxation rate r in embodiment 2 is recorded in 0.55T nuclear magnetic resonance imaging instrument1For 3.7169mM-1*s-1, see Fig. 4；?
Recording the T1 weighted imaging result of sample C in 0.55T nuclear magnetic resonance imaging instrument, level is distinguished clear, sees Fig. 5.
In embodiment 3 test result explanation embodiment 2, sample C relaxation rate r1 is 3.7169mM-1*s-1, can be used as nuclear magnetic resonance, NMR and make
Shadow agent crude drug.
Embodiment 5:
Molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=K；M=Fe；X=0-2；Y=1-4；Z=1-4；And n=0,
Six cyanogen metal complex crystallization Middle molecule formulas of the manganese of 1-20 are KMn [Fe (CN)6](H2O)n, the wherein Manganese hexacyanoferrate potassium of n=0-4
The preparation of crystallization
Weigh 1.0561 grams of K4[Fe(CN)6]·3(H2O) put in 100 milliliters of beakers, add sour: the volume ratio 1: 10 of water
Lactic acid aqueous solution 25ml be completely dissolved, be called for short sample A；Weigh 0.9896 gram of MnCl2.4H2O puts in 100 milliliters of beakers,
Add lactic acid: the lactic acid aqueous solution 25ml of the volume ratio 1: 10 of water is completely dissolved, be called for short sample B；Pour A sample into B sample
In beaker, sealing beaker mouth with sealing compound, under lucifuge, room temperature produces a large amount of fine crystal after standing 12 hours, uses 0.22-0.45 μm
Filtering with microporous membrane, cleans with deionized water and crystallizes to that filtrate PH is unchanged, the crystallization freeze-day with constant temperature at 50 DEG C after cleaning
To constant weight, obtaining molecular formula is KMn [Fe (CN)6](H2O)n, the wherein Manganese hexacyanoferrate potassium crystallization of n=0-4, its X-ray powder
Diffraction pattern is shown in Fig. 6.
Embodiment 6:
Molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=K；M=Fe；X=0-2；Y=1-4；Z=1-4；And n=0,
Six cyanogen metal complex Middle molecule formulas of the manganese of 1-20 are KMn [Fe (CN)6](H2O)n, wherein six cyanogen metal networks of the manganese of n=0-4
The preparation of compound nanoparticle
Weigh 8.50g mannitol, add water to 65ml, add meglumine 6.00g, nicotinic acid 0.0109g, disodium edetate 0.0242g,
Cysteine 0.0180g, polyvinylpyrrolidone 9.00g, be stirred continuously, and is progressively heated to 60 DEG C, maintains 60 DEG C to poly-second
Alkene pyrrolidone is completely dissolved, and solution is that micro-Huang is transparent, is then cooled to room temperature, is called for short sample A.
Weighing molecular formula is KMn [Fe (CN)6](H2O)n, wherein the Manganese hexacyanoferrate crystallization 0.3734g of n=0-4 joins in sample A,
Being stirred continuously, to the complete corrosion of this crystallization, solution is amber transparent, continues stirring 12 hours, and obtaining molecular formula is
KMn[Fe(CN)6](H2O)n, wherein six cyanogen metal complex nano-particle solution of the manganese of n=0-4, are called for short sample B.Record sample B
PH value be 9.0；Transmission electron microscope observation is to nanoparticle equiblibrium mass distribution in the solution in sample B, and particle diameter is at 40-70nm
Scope, is shown in Fig. 7；Transmission electron microscope elementary analysis power spectrum records potassium in sample B: manganese: the atomic ratio of ferrum is about 1: 1: 1,
See Fig. 8；
Embodiment 7:
It is KMn [Fe (CN) by molecular formula prepared in embodiment 66](H2O)n, wherein six cyanogen metal complexes of the manganese of n=0-4
Thing nano-particle solution sample B is configured to the concentration containing manganese 10mM, through 0.22 μm microporous filter membrane aseptic filtration, aseptic subpackaged
In cillin bottle, i.e. prepare six cyanogen metal complex nano-NMR contrast agent of the manganese of liquid, be called for short sample C, be available for vein
Injection uses；
Embodiment 8:
Sample D obtained by embodiment 3 press the dosage of 1ml/300g by tail vein injection to rat body, do nuclear-magnetism common
The radiography that shakes is tested, and records magnetic resonance imaging T2 image and the signal value of rat liver, see Fig. 9 before injection sample D；Injection sample
The magnetic resonance imaging T2 image of rat liver and signal value when 20 minutes after D, be shown in Figure 10.
Rat liver magnetic resonance imaging image after injection sample D is the most dimmed, and signal value is than relative reduction before injection sample D
More than 70%；Rat after injection sample D is raised 2 weeks, and period rat outward appearance and behavior are no abnormal.
Embodiment 9:
Sample C obtained by embodiment 7 press the dosage of 1ml/300g by tail vein injection to rat body, do nuclear-magnetism common
The radiography that shakes is tested, and records magnetic resonance imaging T2 image and the signal value of rat liver, see Figure 11 before injection sample C；Injection
The magnetic resonance imaging T2 image of rat liver and signal value when 20 minutes after sample C, be shown in Figure 12.
Rat liver magnetic resonance imaging image after injection sample C is the most dimmed, and signal value is than relative reduction before injection sample C
More than 65%；Rat after injection sample C is raised 2 weeks, and period rat outward appearance and behavior are no abnormal.
Claims (12)
1. a molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr,
Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanoparticles of the manganese of n=0,1-20 and
Its T2 mri contrast agent purposes.
Compound crystal nanoparticle the most according to claim 1, its preparation method is first to prepare molecular formula to be
AxMny[M(CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn, Fe, Co or Ru；
X=0-2；Y=1-4；Z=1-4；And the compound crystal of n=0,1-20, then prepare molecular formula with this crystallization and be
AxMny[M(CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn, Fe, Co or Ru；
X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanoparticles of the manganese of n=0,1-20.
Compound crystal the most according to claim 2, is characterized in that, with six cyanogen metal complex ion [M (CN)6]n-(M=Cr,
Mn, Fe, Co or Ru, n=3-4) and divalent manganesetion Mn2+By hybrid reaction, obtaining molecular formula is
AxMny[M(CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn, Fe, Co or Ru:
X=0-2；Y=1-4；Z=1-4；And the crystallization of n=0,1-20 compound.
Six cyanogen metal complex ion [M (CN) the most according to claim 36]n-(M=Cr, Mn, Fe, Co or Ru, n=3-4),
It is characterized in that, be dissolved in the aqueous citric acid solution of 0.1%-20% (weight), be dissolved in 0.1%-20% (weight) winestone sour water
Solution, it is dissolved in lactic acid: in the lactic acid aqueous solution of the volume ratio 1: 1-20 of water.
Divalent manganesetion Mn the most according to claim 32+, it is characterized in that, be dissolved in the Fructus Citri Limoniae of 0.1%-20% (weight)
Aqueous acid, it is dissolved in 0.1%-20% (weight) aqueous tartaric acid solution, is dissolved in lactic acid: the breast of the volume ratio 1: 1-20 of water
In aqueous acid.
The most according to claim 3, molecular formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4,
Or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And the crystallization of n=0,1-20 compound, its
Middle a kind of crystalline powder X-ray diffractogram is Fig. 1, and another kind of crystalline powder X-ray diffractogram is Fig. 6, but be not limited to this two
Plant crystallization and x-ray diffractogram of powder thereof.
The most according to claim 3, molecular formula is AxMny [M (CN)6]z·nH2O, wherein A=Li, Na, K, NH4,
Or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And the crystallization of n=0,1-20 compound, knot
Brilliant grain diameter is between 0.2-120 micron.
8., according to claim 3, it is AxMny [M (CN) by molecular formula6]z·(H2O) n, wherein A=Li, Na, K, NH4,
Or Tl；M=Cr, Mn, Fe, Co or Ru；X=0-2；Y=1-4；Z=1-4；And the crystallization corrosion of n=0,1-20 compound
In the aqueous solution that formula is mannitol, meglumine, polyvinylpyrrolidone, nicotinic acid, disodium edetate, cysteine；Or
Corrosion is in the aqueous solution that formula is mannitol, meglumine, polyvinylpyrrolidone, nicotinic acid, disodium edetate；Or corrosion exists
Formula is in the aqueous solution of mannitol, meglumine, polyvinylpyrrolidone, nicotinic acid, cysteine；Or corrosion is sweet at formula
Reveal in the aqueous solution of alcohol, meglumine, polyvinylpyrrolidone, disodium edetate, cysteine；Or corrosion is manna at formula
In alcohol, meglumine, polyvinylpyrrolidone, cigarette aqueous acid；Or corrosion is mannitol, meglumine, polyethylene at formula
Ketopyrrolidine, disodium edetate aqueous solution in；Or corrosion formula be mannitol, meglumine, polyvinylpyrrolidone, half
In the aqueous solution of cystine；Or corrosion is in the aqueous solution that formula is mannitol, meglumine, polyvinylpyrrolidone；Or corrosion
In the aqueous solution that formula is mannitol, meglumine, nicotinic acid, disodium edetate, cysteine, after stirring to solution is transparent,
Stirring is continued transparent to solution after adding polyvinylpyrrolidone；Or corrosion is mannitol, meglumine, nicotinic acid at formula, depends on
Ground acid disodium, aqueous solution in, stir to solution transparent after, add that to continue stirring after polyvinylpyrrolidone transparent to solution；
Or corrosion is in the aqueous solution that formula is mannitol, meglumine, nicotinic acid, cysteine, after stirring to solution is transparent, add
Stirring is continued transparent to solution after polyvinylpyrrolidone；Or corrosion formula be mannitol, meglumine, disodium edetate, half
In the aqueous solution of cystine, after stirring to solution is transparent, continue stirring after adding polyvinylpyrrolidone transparent to solution；Or
Corrosion, in formula is mannitol, meglumine, cigarette aqueous acid, after stirring to solution is transparent, adds polyvinylpyrrolidine
Stirring is continued transparent to solution after ketone；Or corrosion is in the aqueous solution that formula is mannitol, meglumine, disodium edetate, stirring
To solution transparent after, add that to continue stirring after polyvinylpyrrolidone transparent to solution；Or corrosion is mannitol, Portugal at formula
Methylamine, cysteine aqueous solution in, stir to solution transparent after, add and continue stirring after polyvinylpyrrolidone to solution
Transparent；In said process, polyvinylpyrrolidone can substitute with chitosan, or available dextran substitutes, or available carboxyl is right
Rotation sugar acid anhydride substitutes, or available glucosan substitutes, or available Sensor Chip CM 5 substitutes, or available Polyethylene Glycol substitutes, each composition
Consumption be mannitol be 2-20% (weight), meglumine is 2%-20% (weight), and nicotinic acid is 0.01-5.0% (weight), according to ground
Acid disodium is 0.01-5.0% (weight), and cysteine is 0.01%-5.0% (weight), and polyvinylpyrrolidone is 2%-20% (weight
Amount), chitosan is 1.0%-15% (weight), and dextran is 1.0%-15% (weight), and carboxyl dextran is 1.0%-15%
(weight), glucosan is 1.0%-15% (weight), and Sensor Chip CM 5 is 1.0%-15% (weight), and Polyethylene Glycol is 1.0%-20%
(weight), in said process, each composition all dissolves or continues stirring 0.5-36 hour after corrosion, forms the molecule of stable transparent
Formula is AxMny [M (CN)6]z·(H2O) n, wherein A=Li, Na, K, NH4, or Tl；M=Cr, Mn, Fe, Co or
Ru；X=0-2；Y=1-4；Z=1-4；And six cyanogen metal complex nanoparticle and nano-particle solution thereof of n=0,1-20 manganese.
The most according to claim 8, nanoparticle, is characterized in that described nanoparticle is stable between PH 7.6-12.6.
The most according to claim 8, nanoparticle, is characterized in that described Nanoparticle Size is between 0.1nm-200nm.
11. nano-particle solution according to claim 8, divalent manganesetion content is between 0.1-400mM.
12. nanoparticle and nano-particle solution thereof according to claim 8, is characterized in that as T2 mri contrast agent
Crude drug.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012110835A2 (en) * | 2011-02-15 | 2012-08-23 | Semmelweis Egyetem | Prussian blue based nanoparticle as multimodal imaging contrast material |
| CN103251962A (en) * | 2012-02-17 | 2013-08-21 | 苏州迈格锐意医药科技有限公司 | Magnetic resonance contrast material and preparation method thereof, and contrast agent |
| CN105084391A (en) * | 2014-05-05 | 2015-11-25 | 吴学文 | Hexacyanomanganate-metal complex crystallizing nanoparticle and nuclear magnetic resonance contrast agent thereof |
| CN105079824A (en) * | 2014-05-19 | 2015-11-25 | 吴学文 | Hexacyano-metal complex nanoparticle of manganese and nuclear magnetic resonance contrast agent of nanoparticle |
-
2015
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012110835A2 (en) * | 2011-02-15 | 2012-08-23 | Semmelweis Egyetem | Prussian blue based nanoparticle as multimodal imaging contrast material |
| CN103251962A (en) * | 2012-02-17 | 2013-08-21 | 苏州迈格锐意医药科技有限公司 | Magnetic resonance contrast material and preparation method thereof, and contrast agent |
| CN105084391A (en) * | 2014-05-05 | 2015-11-25 | 吴学文 | Hexacyanomanganate-metal complex crystallizing nanoparticle and nuclear magnetic resonance contrast agent thereof |
| CN105079824A (en) * | 2014-05-19 | 2015-11-25 | 吴学文 | Hexacyano-metal complex nanoparticle of manganese and nuclear magnetic resonance contrast agent of nanoparticle |
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