CN103961725A - Magnetic resonance imaging material and preparation method thereof - Google Patents
Magnetic resonance imaging material and preparation method thereof Download PDFInfo
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- CN103961725A CN103961725A CN201310041168.2A CN201310041168A CN103961725A CN 103961725 A CN103961725 A CN 103961725A CN 201310041168 A CN201310041168 A CN 201310041168A CN 103961725 A CN103961725 A CN 103961725A
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Abstract
The invention provides a magnetic resonance imaging material and a preparation method thereof. The magnetic resonance imaging material is Prussian blue doped with paramagnetic metal ions, which can be Cr<3+>, Ce<3+>, Pr<3+>, Nd<3+>, Pm<3+>, Sm<3+>, Eu<3+>, Tb<3+>, Dy<3+>, Ho<3+>, Er<3+>, Tm<3+>, Yb<3+>, Cr<2+>, Co<2+>, Ni<2+>, Cu<2+>, or Eu<2+>. The magnetic resonance imaging material containing the paramagnetic metal ions has stable performance, if the material is placed in hydrochloric acid with pH of 1, normal saline and pure water for 24h, the solution has no significant color change, and is clear and transparent. In the hydrochloric acid with pH of 1, normal saline and water, the content of free metals in the solution is determined to be only several PPM. With good stability, difficult decomposition and ionization, low toxicity, especially stable existence in strong acid solution without decomposition, the magnetic resonance imaging material can be used as injection and oral administration magnetic resonance contrast agents.
Description
Technical field
The present invention relates to mr imaging technique field, particularly relate to a kind of magnetic resonance radiography material and preparation method thereof.
Background technology
Magnetic resonance radiography material is the compound that a class contains one or more paramagnetic metal ions.These compounds can change the relaxation time T of in-vivo tissue
1or T
2, make the Enhancement contrast between normal structure and organ and pathological tissues and organ, thereby reach the object of medical diagnosis.
At present, there are several ions to be widely used on magnetic resonance contrast agent, for example: in some commercialization magnetic resonance contrast agents, to contain Fe
2+, Fe
3+, Mn
2+or Gd
3+.Other metal ions, due to structural unstability, seldom can use as magnetic resonance contrast agent.Out mostly there is very strong toxicity because these metals are free in vivo, and be difficult to by metabolism, so very harmful.
Prussian blue is a kind of constitutionally stable coordination compound, contains [Fe (CN) in structure
6]
4-, can form constitutionally stable coordination compound with other metal, water insoluble and organic solvent, there is less Ksp, be difficult in vivo decomposing, be difficult to dissociate metal ion, so toxic and side effects is lower, this architectural characteristic, makes this compounds be suitable as magnetic resonance radiography material.
Summary of the invention
Based on this, now provide a kind of Stability Analysis of Structures, magnetic resonance radiography material that toxicity is low and preparation method thereof.
A kind of magnetic resonance radiography material, described magnetic resonance radiography material is Prussian blue doped with paramagnetic metal ion, wherein, described paramagnetic metal ion is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+, Yb
3+, Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+.
In an embodiment, the chemical formula of described magnetic resonance radiography material is A therein
3x[D
iII yfe
iII 1-y]
(4-x)[Fe
iI(CN)
6]
3nH
2o;
Wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, 0≤x≤1,0<y≤1, n=1 ~ 16;
D is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+or Yb
3+.
In an embodiment, the chemical formula of described magnetic resonance radiography material is A therein
3x[E
iI yfe
iII (3-2y)/3]
(4-x)[Fe
iI(CN)
6]
3nH
2o;
Wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, 0≤x≤1,0<y≤1, n=1 ~ 16;
E is Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+.
A preparation method for magnetic resonance radiography material, comprises the following steps:
Prepare respectively the A that concentration is 0.1mmol/L ~ 2000mmol/L
4[Fe
iI(CN)
6] solubility paramagnetic metal saline solution that aqueous solution, the concentration soluble iron saline solution that is 0.1mmol/L ~ 2000mmol/L and concentration are 0.1mmol/L ~ 2000mmol/L, wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, in described solubility paramagnetic metal saline solution, containing paramagnetic metal ion, described paramagnetic metal ion is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+or Yb
3+, Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+; And
By described A
4[Fe
iI(CN)
6] aqueous solution mixs homogeneously with described soluble iron saline solution and described solubility paramagnetic metal saline solution, controlling reaction temperature is 0 ~ 100 DEG C, fully after reaction, remove impurity, after dry, obtain magnetic resonance radiography material, wherein, described magnetic resonance radiography material is Prussian blue doped with paramagnetic metal ion.
Therein in an embodiment, at least one in chloride, nitrate and carbonate that the solubility paramagnetic metal salt in described solubility paramagnetic metal saline solution is described paramagnetic metal ion.
In an embodiment, the soluble ferric iron salt in described soluble iron saline solution is at least one in anhydrous ferric chloride, ferric chloride hexahydrate, ferric nitrate, iron sulfate, iron acetate, ferric citrate and ferrous gluconate therein.
Therein in an embodiment, described in remove impurity step and comprise: use the method for centrifugal, dialysis or ultrafiltration, remove unreacted raw material and byproduct of reaction.
In an embodiment, comprise the following steps therein:
Prepare respectively the A that concentration is 0.1mmol/L ~ 2000mmol/L
4[Fe
iI(CN)
6] the first solubility paramagnetic metal saline solution that aqueous solution, the concentration soluble iron saline solution that is 0.1mmol/L ~ 2000mmol/L and concentration are 0.1mmol/L ~ 2000mmol/L, wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, in described the first solubility paramagnetic metal saline solution, containing paramagnetic metal ion D, D is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+or Yb
3+; And
By described A
4[Fe
iI(CN)
6] aqueous solution mixs homogeneously with described soluble iron saline solution and described the first solubility paramagnetic metal saline solution, controlling reaction temperature is 0 ~ 100 DEG C, fully after reaction, removes impurity, obtaining chemical formula after dry is A
3x[D
iII yfe
iII 1-y]
(4-x)[Fe
iI(CN)
6]
3nH
2the magnetic resonance radiography material of O, wherein, 0≤x≤1,0<y≤1, n=1 ~ 16.
Therein in an embodiment, the first solubility paramagnetic metal salt in described the first solubility paramagnetic metal saline solution is at least one in chloride, nitrate and the carbonate of paramagnetic metal ion D.
In an embodiment, comprise the following steps therein:
Prepare respectively the A that concentration is 0.1mmol/L ~ 2000mmol/L
4[Fe
iI(CN)
6] the second solubility paramagnetic metal saline solution that aqueous solution, the concentration soluble iron saline solution that is 0.1mmol/L ~ 2000mmol/L and concentration are 0.1mmol/L ~ 2000mmol/L, wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, in described the second solubility paramagnetic metal saline solution, containing paramagnetic metal ion E, E is Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+; And
By described A
4[Fe
iI(CN)
6] aqueous solution mixs homogeneously with described soluble iron saline solution and described the second solubility paramagnetic metal saline solution, controlling reaction temperature is 0 ~ 100 DEG C, fully after reaction, removes impurity, obtaining chemical formula after dry is A
3x[E
iI yfe
iII (3-2y)/3]
(4-x)[Fe
iI(CN)
6]
3nH
2the magnetic resonance radiography material of O, wherein, 0≤x≤1,0<y≤1, n=1 ~ 16.
The above-mentioned magnetic resonance radiography material containing paramagnetic metal ion, stable performance, as placed after 24 hours in the hydrochloric acid of pH=1, in normal saline and pure water, solution colour is without significant change, and clear, measures free tenor in solution, in the hydrochloric acid of pH=1, in normal saline and be only all several PPM in water, good stability, be difficult for decomposition and ionization, toxicity is low, particularly can stable existence in strong acid solution and do not decompose, can serve as injection and the use of oral magnetic resonance contrast agent.
Brief description of the drawings
Fig. 1 is the prepared KYb of embodiment 1
iII 0.1fe
iII 0.9[Fe
iI(CN)
6] 4H
2o, the prepared KDy of embodiment 2
iII 0.1fe
iII 0.9[Fe
iI(CN)
6] 4H
2o, the prepared KCo of embodiment 3
iIfe
iII 1/3[Fe
iI(CN)
6] 4H
2o, the prepared KCu of embodiment 4
iIfe
iII 1/3[Fe
iI(CN)
6] 4H
2the x-ray diffraction pattern of O magnetic resonance radiography material;
Fig. 2 is Prussian blue crystal structure figure;
Fig. 3 is stability experiment result;
Fig. 4 is the prepared KYb of embodiment 1
iII 0.1fe
iII 0.9[Fe
iI(CN)
6] 4H
2o is relaxation rate experimental result under 1.5T magnetic field;
Fig. 5 is the prepared KDy of embodiment 2
iII 0.1fe
iII 0.9[Fe
iI(CN)
6] 4H
2o is relaxation rate experimental result under 1.5T magnetic field;
Fig. 6 is the prepared KCo of embodiment 3
iIfe
iII 1/3[Fe
iI(CN)
6] 4H
2o is relaxation rate experimental result under 1.5T magnetic field;
Fig. 7 is the prepared KCu of embodiment 4
iIfe
iII 1/3[Fe
iI(CN)
6] 4H
2o is relaxation rate experimental result under 1.5T magnetic field;
Fig. 8 is the prepared KYb of embodiment 1
iII 0.1fe
iII 0.9[Fe
iI(CN)
6] 4H
2the cytotoxicity experiment result of O;
Fig. 9 is the KYb of preparation in embodiment 1
iII 0.1fe
iII 0.9[Fe
iI(CN)
6] 4H
2the external imaging experiment result of O.
Detailed description of the invention
For above-mentioned purpose of the present invention, feature and advantage can be become apparent more, below the specific embodiment of the present invention is described in detail.A lot of details are set forth in the following description so that fully understand the present invention.But the present invention can implement to be much different from alternate manner described here, and those skilled in the art can do similar improvement without prejudice to intension of the present invention in the situation that, and therefore the present invention is not subject to the restriction of following public concrete enforcement.
The magnetic resonance radiography material of one embodiment, magnetic resonance radiography material is Prussian blue doped with paramagnetic metal ion, wherein, paramagnetic metal ion is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+, Yb
3+, Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+.
Above-mentioned magnetic resonance radiography material can have the chemical formula of (I) or (II) structure:
A
3x[D
III yFe
III 1-y]
(4-x)[Fe
II(CN)
6]
3·nH
2O（Ⅰ）
A
3x[E
II yFe
III (3-2y)/3]
(4-x)[Fe
II(CN)
6]
3·nH
2O（Ⅱ）
Wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, 0≤x≤1,0<y≤1, n=1 ~ 16;
D is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+or Yb
3+;
E is Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+.
The above-mentioned magnetic resonance radiography material containing paramagnetic metal ion, stable performance, as placed after 24 hours in the hydrochloric acid of pH=1, in normal saline and pure water, solution colour is without significant change, and clear, measures free tenor in solution, in the hydrochloric acid of pH=1, in normal saline and be only all several PPM in water, good stability, be difficult for decomposition and ionization, toxicity is low, particularly can stable existence in strong acid solution and do not decompose, can serve as injection and the use of oral magnetic resonance contrast agent.
The preparation method of above-mentioned magnetic resonance radiography material, comprises the following steps:
Step 1, prepare the A that concentration is 0.1mmol/L ~ 2000mmol/L respectively
4[Fe
iI(CN)
6] solubility paramagnetic metal saline solution that aqueous solution, the concentration soluble iron saline solution that is 0.1mmol/L ~ 2000mmol/L and concentration are 0.1mmol/L ~ 2000mmol/L, wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, in solubility paramagnetic metal saline solution, containing paramagnetic metal ion, paramagnetic metal ion is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+or Yb
3+, Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+.
Wherein, soluble ferric iron salt in soluble iron saline solution can be the conventional soluble ferric iron salt in this area, or insoluble iron salt is generated to soluble ferric iron salt through reactions such as soda acid oxidations, be preferably at least one in anhydrous ferric chloride, ferric chloride hexahydrate, ferric nitrate, iron sulfate, iron acetate, ferric citrate and ferrous gluconate.
Solubility paramagnetic metal salt in solubility paramagnetic metal saline solution can be the conventional solubility paramagnetic metal salt in this area, or insoluble paramagnetic metal salt is generated to solubility paramagnetic metal salt through reactions such as soda acid oxidations, be preferably at least one in chloride, nitrate and the carbonate of paramagnetic metal ion.
Step 2, by A
4[Fe
iI(CN)
6] aqueous solution mixs homogeneously with soluble iron saline solution and solubility paramagnetic metal saline solution, controlling reaction temperature is 0 ~ 100 DEG C, fully after reaction, removes impurity, after being dried, obtains magnetic resonance radiography material, wherein, magnetic resonance radiography material is Prussian blue doped with paramagnetic metal ion.
In this step, A
4[Fe
iI(CN)
6] aqueous solution fully reacts with soluble iron saline solution and solubility paramagnetic metal saline solution, generates magnetic resonance radiography material, wherein paramagnetic metal ion part replaces the Fe in Prussian blue
3+.
Remove the purification process that impurity step can be selected centrifugal, dialysis or ultrafiltration, remove unreacted raw material and byproduct of reaction.
Concrete, A
3x[D
iII yfe
iII 1-y]
(4-x)[Fe
iI(CN)
6]
3nH
2the preparation method of O magnetic resonance radiography material, comprises the following steps:
Step 1, prepare the A that concentration is 0.1mmol/L ~ 2000mmol/L respectively
4[Fe
iI(CN)
6] the first solubility paramagnetic metal saline solution that aqueous solution, the concentration soluble iron saline solution that is 0.1mmol/L ~ 2000mmol/L and concentration are 0.1mmol/L ~ 2000mmol/L, wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, in the first solubility paramagnetic metal saline solution, containing paramagnetic metal ion D, D is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+or Yb
3+.
The first solubility paramagnetic metal salt in the first solubility paramagnetic metal saline solution can be at least one in chloride, nitrate and the carbonate of paramagnetic metal ion D.
Step 2, by A
4[Fe
iI(CN)
6] aqueous solution mixs homogeneously with soluble iron saline solution and the first solubility paramagnetic metal saline solution, controlling reaction temperature is 0 ~ 100 DEG C, fully after reaction, removes impurity, obtaining chemical formula after dry is A
3x[D
iII yfe
iII 1-y]
(4-x)[Fe
iI(CN)
6]
3nH
2the magnetic resonance radiography material of O, wherein, 0≤x≤1,0<y≤1, n=1 ~ 16.
A
3x[E
iI yfe
iII (3-2y)/3]
(4-x)[Fe
iI(CN)
6]
3nH
2the preparation method of O magnetic resonance radiography material, comprises the following steps:
Step 1, prepare the A that concentration is 0.1mmol/L ~ 2000mmol/L respectively
4[Fe
iI(CN)
6] the second solubility paramagnetic metal saline solution that aqueous solution, the concentration soluble iron saline solution that is 0.1mmol/L ~ 2000mmol/L and concentration are 0.1mmol/L2000mmol/L, wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, in the second solubility paramagnetic metal saline solution, containing paramagnetic metal ion E, E is Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+.
The second solubility paramagnetic metal salt in the second solubility paramagnetic metal saline solution is at least one in chloride, nitrate and the carbonate of paramagnetic metal ion E.
Step 2, by A
4[Fe
iI(CN)
6] aqueous solution mixs homogeneously with soluble iron saline solution and the second solubility paramagnetic metal saline solution, controlling reaction temperature is 0 ~ 100 DEG C, fully after reaction, removes impurity, obtaining chemical formula after dry is A
3x[E
iI yfe
iII (3-2y)/3]
(4-x)[Fe
iI(CN)
6]
3nH
2the magnetic resonance radiography material of O, wherein, 0≤x≤1,0<y≤1, n=1 ~ 16.
The preparation method technique of above-mentioned magnetic resonance radiography material is simple, and raw material is easy to get.The magnetic resonance radiography material making is compared with conventional magnetic resonance radiography material, and relaxation rate is higher, and radiography effect is better.
Below in conjunction with drawings and the specific embodiments, magnetic resonance radiography material and preparation method thereof is further elaborated.
Embodiment 1
Take the K of 4.224g
4[Fe
iI(CN)
6] 3H
2o is dissolved in 1000mL water, obtains the K of 10mmol/L
4[Fe
iI(CN)
6] aqueous solution, obtain solution C;
By 2.433g FeCl
36H
2o is dissolved in 900mL water, stirs, and obtains the ferric chloride solution of 10mmol/L;
By 0.388g YbCl
36H
2o is dissolved in 100mL water, stirs, and obtains the Ytterbium trichloride solution of 10mmol/L;
Above-mentioned iron chloride and Ytterbium trichloride solution are mixed, then be added drop-wise to fast in solution C, mixing speed is 1000rpm, and reaction temperature is 15 DEG C, response time is 60min, reacted solution is dialysed, and then centrifugal, speed is 10000rpm, time is 10min, take out precipitation, after lyophilization, obtain magnetic resonance radiography material.As shown in Figure 1, its structure is similar to Prussian blue (being abbreviated as PB) for x-ray diffraction pattern, and the position of part Fe is replaced by Yb; This compound is similar to the crystal formation (as shown in Figure 2) of PB, is cubic system, and space group is
cell parameter is:
its elementary analysis data are as follows: K:9.98%, Yb:4.43%, Fe:27.2%, CN:39.9%; In the known compound of thermogravimetric analysis, contain 4 water of crystallization, its chemical formula is KYb
iII 0.1fe
iII 0.9[Fe
iI(CN)
6] 4H
2o(is abbreviated as YbPB)
Embodiment 2
Take the K of 4.224g
4[Fe
iI(CN)
6] 3H
2o is dissolved in 1000mL water, obtains the K of 10mmol/L
4[Fe
iI(CN)
6] aqueous solution, obtain solution C;
By 2.433g FeCl
36H
2o is dissolved in 900mL water, stirs, and obtains the ferric chloride solution of 10mmol/L;
By 0.377g DyCl
36H
2o is dissolved in 100mL water, stirs, and obtains the Ytterbium trichloride solution of 10mmol/L;
Above-mentioned iron chloride and Dysprosium trichloride solution are mixed, then be added drop-wise to fast in solution C, mixing speed is 800rpm, and reaction temperature is 25 DEG C, response time is 40min, reacted solution is dialysed, and then centrifugal, speed is 8000rpm, time is 5min, take out precipitation, after drying, obtain magnetic resonance radiography material.As shown in Figure 1, its structure is similar to Prussian blue (being abbreviated as PB) for x-ray diffraction pattern, and the position of part Fe is replaced by Dy; This compound is similar to the crystal formation (as shown in Figure 2) of PB, is cubic system, and space group is
cell parameter is:
its elementary analysis data are as follows: K:10.01%, Dy:4.16%, Fe:27.3%, CN:40.4%; In the known compound of thermogravimetric analysis, contain 4 water of crystallization.Its chemical formula is KDy
iII 0.1fe
iII 0.9[Fe
iI(CN)
6] 4H
2o(is abbreviated as DyPB).
Embodiment 3
Take the K of 4.224g
4[Fe
iI(CN)
6] 3H
2o is dissolved in 1000mL water, obtains the K of 10mmol/L
4[Fe
iI(CN)
6] aqueous solution, obtain solution C;
By 0.891g FeCl
36H
2o is dissolved in 900mL water, stirs, and obtains the ferric chloride solution of 3.67mmol/L;
By 2.379g CoCl
26H
2o is dissolved in 100mL water, stirs, and obtains the cobalt chloride solution of 100mmol/L;
Above-mentioned iron chloride and cobalt chloride solution are mixed, then be added drop-wise to fast in solution C, mixing speed is 800rpm, and reaction temperature is 35 DEG C, and the response time is 30min, by reacted solution centrifugal, speed is 6000rpm, and the time is 10min, takes out precipitation, after oven dry, obtain magnetic resonance radiography material.As shown in Figure 1, its structure is to Prussian blue similar for X-ray diffraction, and the position of part Fe is replaced by Co; This compound is cubic system, and space group is
cell parameter is:
its elementary analysis data are as follows: K:9.7%, and Co:14.7%, Fe:18.6%, CN:38.9%, meets with molecular formula; In the known compound of thermogravimetric analysis, contain 4 water of crystallization.Its chemical formula is: KCo
iIfe
iII 1/3[Fe
iI(CN)
6] 4H
2o(is abbreviated as CoPB)
Embodiment 4
Take the K of 4.224g
4[Fe
iI(CN)
6] 3H
2o is dissolved in 1000mL water, obtains the K of 10mmol/L
4[Fe
iI(CN)
6] aqueous solution, obtain solution C;
By 0.891g FeCl
36H
2o is dissolved in 900mL water, stirs, and obtains the ferric chloride solution of 3.7mmol/L;
By 2.5g CuSO
45H
2o is dissolved in 100mL water, stirs, and obtains the cobalt chloride solution of 100mmol/L;
Above-mentioned iron sulfate and copper-bath are mixed, then be added drop-wise to fast in solution C, mixing speed is 600rpm, and reaction temperature is 30 DEG C, and the response time is 30min, by reacted solution centrifugal, speed is 4000rpm, and the time is 10min, takes out precipitation, after oven dry, obtain magnetic resonance radiography material.As shown in Figure 1, its structure is to Prussian blue similar for X-ray diffraction, and the position of part Fe is replaced by Cu, forms solid solution; This compound is cubic system, and space group is
cell parameter is:
elementary analysis is known: K:10.4%, and Cu:8.5%, Fe:20%, CN:41.8% contains 4 water of crystallization in the known compound of thermogravimetric analysis, and this magnetic resonance radiography materials chemistry formula is KCu
iIfe
iII 1/3[Fe
iI(CN)
6] 4H
2o(CuPB).
Stability experiment
The YbPB magnetic resonance radiography material making in embodiment 1 is put into respectively to hydrochloric acid, normal saline and the pure water of pH=1, is placed after 24 hours, observe its steadiness as follows:
Solution colour is without significant change, and clear, measures CN in solution
-and Yb
3+content, in the hydrochloric acid of pH=1, in normal saline and be only all several PPM in pure water, as shown in Figure 3, CN
-content is well below the amount in smoking human body, Yb
3+content is also far smaller than toxic dose, illustrates that the stability of YbPB is fine, particularly can stable existence in acid, do not decompose, and toxicity is little, and not only can serve as ejection preparation, can also serve as oral administration nanometer magnetic resonance radiography material.
Relaxation rate experiment
Relaxation rate is the important indicator of evaluating magnetic resonance radiography material radiography effect, get the magnetic resonance radiography material making in embodiment 1 ~ 4 some, diluted respectively the solution for variable concentrations, get 500 μ L and put into sample cell, sample cell is put into 37 DEG C of water-baths and heat 15min, then put into after instrument probe 5min and start to measure, magnetic field intensity is 1.5T, meanwhile, we get commercially available prod magnevist (Gd-DTPA), as reference.
As shown in Figure 4, Figure 5, Figure 6 and Figure 7, under 1.5T magnetic field, the relaxation rate result of the different magnetic resonance radiography materials containing paramagnetic metal ion is as shown in table 1 for relaxation rate result.
The relaxation rate of the different magnetic resonance radiography materials containing paramagnetic metal ion of table 1
| Contrast agent | Radiography material | R 1(mM -1s -1) | Magnetic field intensity |
| Embodiment 1 | YbPB | 15.60 | 1.5T |
| Embodiment 2 | DyPB | 12.02 | 1.5T |
| Embodiment 3 | CoPB | 12.02 | 1.5T |
| Embodiment 4 | CuPB | 7.50 | 1.5T |
| With reference to experiment | Gd-DTPA | 3.27 | 1.5T |
As can be seen from the above table, containing the magnetic resonance radiography material of paramagnetic metal ion, external relaxation rate R
1very high, be 3 ~ 5 times of current commercial goods magnevist, illustrate that this type of material uses little dosage, can reach diagnostic purpose, its toxicity also can significantly reduce.
Toxicity test
The YbPB that embodiment 1 is made is mixed with variable concentrations, puts into respectively cell culture fluid, carries out cell culture, and the time is 12 hours and 24 hours, and result as shown in Figure 8.
As shown in Figure 8, under various concentration, do not find that cell has any abnormal, illustrate that this magnetic resonance radiography material is without obvious toxic-side effects.
External imaging experiment
To concentration be 0.1,0.3, the YbPB solution of 0.5mmol/L carries out external imaging experiment, result is as shown in Figure 9.
As shown in Figure 9, along with the increase of YbPB solution concentration, imaging effect obviously increases, and in the time that YbPB solution concentration is 0.3mmol/L, imaging effect is better, illustrate that YbPB magnetic resonance radiography material in use amount hour, just can reach good imaging effect, reach diagnostic purpose.
The above embodiment has only expressed several embodiment of the present invention, and it describes comparatively concrete and detailed, but can not therefore be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that for the person of ordinary skill of the art, without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.Therefore, the protection domain of patent of the present invention should be as the criterion with claims.
Claims (10)
1. a magnetic resonance radiography material, is characterized in that, described magnetic resonance radiography material is Prussian blue doped with paramagnetic metal ion, and wherein, described paramagnetic metal ion is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+, Yb
3+, Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+.
2. magnetic resonance radiography material according to claim 1, is characterized in that, the chemical formula of described magnetic resonance radiography material is A
3x[D
iII yfe
iII 1-y]
(4-x)[Fe
iI(CN)
6]
3nH
2o;
Wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, 0≤x≤1,0<y≤1, n=1 ~ 16;
D is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+or Yb
3+.
3. magnetic resonance radiography material according to claim 1, is characterized in that, the chemical formula of described magnetic resonance radiography material is A
3x[E
iI yfe
iII (3-2y)/3]
(4-x)[Fe
iI(CN)
6]
3nH
2o;
Wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, 0≤x≤1,0<y≤1, n=1 ~ 16;
E is Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+.
4. a preparation method for magnetic resonance radiography material, is characterized in that, comprises the following steps:
Prepare respectively the A that concentration is 0.1mmol/L ~ 2000mmol/L
4[Fe
iI(CN)
6] solubility paramagnetic metal saline solution that aqueous solution, the concentration soluble iron saline solution that is 0.1mmol/L ~ 2000mmol/L and concentration are 0.1mmol/L ~ 2000mmol/L, wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, in described solubility paramagnetic metal saline solution, containing paramagnetic metal ion, described paramagnetic metal ion is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+or Yb
3+, Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+; And
By described A
4[Fe
iI(CN)
6] aqueous solution mixs homogeneously with described soluble iron saline solution and described solubility paramagnetic metal saline solution, controlling reaction temperature is 0 ~ 100 DEG C, fully after reaction, remove impurity, after dry, obtain magnetic resonance radiography material, wherein, described magnetic resonance radiography material is Prussian blue doped with paramagnetic metal ion.
5. the preparation method of magnetic resonance radiography material according to claim 4, it is characterized in that at least one in chloride, nitrate and carbonate that the solubility paramagnetic metal salt in described solubility paramagnetic metal saline solution is described paramagnetic metal ion.
6. the preparation method of magnetic resonance radiography material according to claim 4, it is characterized in that, the soluble ferric iron salt in described soluble iron saline solution is at least one in anhydrous ferric chloride, ferric chloride hexahydrate, ferric nitrate, iron sulfate, iron acetate, ferric citrate and ferrous gluconate.
7. the preparation method of magnetic resonance radiography material according to claim 4, is characterized in that, described in remove impurity step and comprise: use the method for centrifugal, dialysis or ultrafiltration, remove unreacted raw material and byproduct of reaction.
8. the preparation method of magnetic resonance radiography material according to claim 4, is characterized in that, comprises the following steps:
Prepare respectively the A that concentration is 0.1mmol/L ~ 2000mmol/L
4[Fe
iI(CN)
6] the first solubility paramagnetic metal saline solution that aqueous solution, the concentration soluble iron saline solution that is 0.1mmol/L ~ 2000mmol/L and concentration are 0.1mmol/L ~ 2000mmol/L, wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, in described the first solubility paramagnetic metal saline solution, containing paramagnetic metal ion D, D is Cr
3+, Ce
3+, Pr
3+, Nd
3+, Pm
3+, Sm
3+, Eu
3+, Tb
3+, Dy
3+, Ho
3+, Er
3+, Tm
3+or Yb
3+; And
By described A
4[Fe
iI(CN)
6] aqueous solution mixs homogeneously with described soluble iron saline solution and described the first solubility paramagnetic metal saline solution, controlling reaction temperature is 0 ~ 100 DEG C, fully after reaction, removes impurity, obtaining chemical formula after dry is A
3x[D
iII yfe
iII 1-y]
(4-x)[Fe
iI(CN)
6]
3nH
2the magnetic resonance radiography material of O, wherein, 0≤x≤1,0<y≤1, n=1 ~ 16.
9. the preparation method of magnetic resonance radiography material according to claim 8, it is characterized in that, the first solubility paramagnetic metal salt in described the first solubility paramagnetic metal saline solution is at least one in chloride, nitrate and the carbonate of paramagnetic metal ion D.
10. the preparation method of magnetic resonance radiography material according to claim 4, is characterized in that, comprises the following steps:
Prepare respectively the A that concentration is 0.1mmol/L ~ 2000mmol/L
4[Fe
iI(CN)
6] the second solubility paramagnetic metal saline solution that aqueous solution, the concentration soluble iron saline solution that is 0.1mmol/L ~ 2000mmol/L and concentration are 0.1mmol/L ~ 2000mmol/L, wherein, A is Li
+, Na
+, K
+, Rb
+, Cs
+, NH
4 +or Tl
+, in described the second solubility paramagnetic metal saline solution, containing paramagnetic metal ion E, E is Cr
2+, Co
2+, Ni
2+, Cu
2+or Eu
2+; And
By described A
4[Fe
iI(CN)
6] aqueous solution mixs homogeneously with described soluble iron saline solution and described the second solubility paramagnetic metal saline solution, controlling reaction temperature is 0 ~ 100 DEG C, fully after reaction, removes impurity, obtaining chemical formula after dry is A
3x[E
iI yfe
iII (3-2y)/3]
(4-x)[Fe
iI(CN)
6]
3nH
2the magnetic resonance radiography material of O, wherein, 0≤x≤1,0<y≤1, n=1 ~ 16.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412927A (en) * | 2015-12-22 | 2016-03-23 | 哈尔滨工业大学 | Prussian blue nano particle with high photo-thermal performance and of manganese-doped hollow structure and preparation method of prussian blue nano particle |
| CN109876160A (en) * | 2019-02-21 | 2019-06-14 | 南方医科大学南方医院 | A kind of copper and iron antimony sulphur nano particle and its preparation method and application |
| CN111821281A (en) * | 2020-07-31 | 2020-10-27 | 湖北大学 | Gd/Tm-PB nano-particles, preparation method thereof, multifunctional composite material, and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100254912A1 (en) * | 2009-04-03 | 2010-10-07 | Kent State University | Gadolinium containing prussian blue nanoparticles as nontoxic MRI contrast agents having high relaxivity |
| WO2012110835A2 (en) * | 2011-02-15 | 2012-08-23 | Semmelweis Egyetem | Prussian blue based nanoparticle as multimodal imaging contrast material |
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| US20100254912A1 (en) * | 2009-04-03 | 2010-10-07 | Kent State University | Gadolinium containing prussian blue nanoparticles as nontoxic MRI contrast agents having high relaxivity |
| WO2012110835A2 (en) * | 2011-02-15 | 2012-08-23 | Semmelweis Egyetem | Prussian blue based nanoparticle as multimodal imaging contrast material |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105412927A (en) * | 2015-12-22 | 2016-03-23 | 哈尔滨工业大学 | Prussian blue nano particle with high photo-thermal performance and of manganese-doped hollow structure and preparation method of prussian blue nano particle |
| CN105412927B (en) * | 2015-12-22 | 2019-01-08 | 哈尔滨工业大学 | A kind of preparation method of the additive Mn hollow structure prussian blue nano particle with high light thermal property |
| CN109876160A (en) * | 2019-02-21 | 2019-06-14 | 南方医科大学南方医院 | A kind of copper and iron antimony sulphur nano particle and its preparation method and application |
| CN111821281A (en) * | 2020-07-31 | 2020-10-27 | 湖北大学 | Gd/Tm-PB nano-particles, preparation method thereof, multifunctional composite material, and preparation method and application thereof |
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