CN1321122C - Water heating synthesis of yttrium-diethyltriamine pentacetate - Google Patents
Water heating synthesis of yttrium-diethyltriamine pentacetate Download PDFInfo
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- CN1321122C CN1321122C CNB2005100238006A CN200510023800A CN1321122C CN 1321122 C CN1321122 C CN 1321122C CN B2005100238006 A CNB2005100238006 A CN B2005100238006A CN 200510023800 A CN200510023800 A CN 200510023800A CN 1321122 C CN1321122 C CN 1321122C
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- gadolinium
- pentaacetic acid
- diethylenetriamine pentaacetic
- sesquioxide
- dtpa
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Abstract
The present invention relates to a hydrothermal synthesis method for gadolinium (namely Gd)-diethylentriaminepentaacetic acid (namely DTPA) contrast media of magnetic resonance imaging (MRI), which belongs to the technical field of inorganic synthesis of coordination chemistry. The present invention has the technical scheme that gadolinium oxide and diethylenetriaminepentaacetic acid are used; gadolinium-diethylenetriaminepentaacetic acid is generated through hydrothermal synthesis. The present invention has the advantages of high reaction speed, complete reaction, high yield, few impurity and simple separation process. The method of the present invention is especially suitable for preparing gadolinium-diethylenetriaminepentaacetic acid contrast media of magnetic resonance imaging.
Description
Affiliated technical field
The present invention relates to the synthetic gadolinium (Gadolinium of a kind of hydro-thermal, be Gd)-diethylenetriamine pentaacetic acid (has another name called Pentetic Acid Diethylentriaminepentaacetic acid, be DTPA) method of magnetic resonance imaging contrast (MRI), belong to inorganic coordination chemistry synthetic technical field.
Background technology
Mr imaging technique has a wide range of applications at biology and medical field, a kind of common medical diagnosis means have been become, gadolinium-diethylenetriamine pentaacetic acid, having another name called the gadolinium Pentetic Acid is Gadolinium-Diethylentriaminepentaacetic acid abbreviation Gd-DTPA, is widely used a kind of magnetic resonance imaging contrast.The existing synthetic gadolinium-method of diethylenetriamine pentaacetic acid magnetic resonance imaging contrast is to make raw material with the muriate of gadolinium, adding diethylenetriamine pentaacetic acid prepares, because Gadolinium trichloride is poisonous, so in product, be mixed with excessive gadolinium ion easily, increase toxicity ([1] Kunimasa JI, Inui KI, Hori R.et al., Mannan-Coated Liposome Delivery ofGadolimium-Diethylentriaminepentaacetic acid, a contrast agent for usein magnetic resonance imaging (gadolinium Pentetic Acid seminolipid, magnetic resonance imaging contrast) .[J] .Chem.Pharm.Bull., 1992.40 (9): 2565-2567).Also the oxide compound of useful gadolinium is a feedstock production, but long reaction time, productive rate is low, impurity is many, and ([2] patent No. and title are respectively US5560903 and the ' United States Patent (USP) of Method of enhancing paramagnetism in chelates for MRI ' (strengthening paramagnetic method with inner complex in nuclear magnetic resonance) to separation difficulty.
Summary of the invention
The objective of the invention is to release the method for the synthetic gadolinium-diethylenetriamine pentaacetic acid of a kind of hydro-thermal, this method responds fully, productive rate height, advantage such as impurity is few, and the separated product process is simple.
The present invention realizes that the technical scheme of above-mentioned purpose is to adopt gadolinium sesquioxide and diethylenetriamine pentaacetic acid, and is synthetic by hydro-thermal, generates gadolinium-diethylenetriamine pentaacetic acid.
Now describe technical scheme of the present invention in detail.
The method of the synthetic gadolinium-diethylenetriamine pentaacetic acid of a kind of hydro-thermal is characterized in that, concrete building-up process:
Behind the first step gadolinium sesquioxide and the diethylenetriamine pentaacetic acid mixing, add in the hydrothermal reactor, add entry again, become suspension liquid, put into 80～200 ℃ of environment following 10 minutes～10 hours, and took out cooling, get gadolinium-diethylenetriamine pentaacetic acid solution, the mol ratio of gadolinium sesquioxide, diethylenetriamine pentaacetic acid and water is 1: 2: (20～600), chemical reaction skeleton symbol: Gd
2O
3+ DTPA--〉Gd (DTPA)+3H
2O;
After the solution cooling that the second step the first step makes, filter, evaporate, get crystal, gadolinium-diethylenetriamine pentaacetic acid crude product;
The 3rd step was used the ordinary method ethyl alcohol recrystallization, and vacuum-drying gets the pure product of gadolinium-diethylenetriamine pentaacetic acid, and the mol ratio of gadolinium sesquioxide and the pure product of gadolinium-diethylenetriamine pentaacetic acid is 1: 1.8.
The invention has the beneficial effects as follows:
1. speed of response is fast
Under hydrothermal condition, can adopt the temperature more much higher (more than 100 ℃ than reactant aqueous solution commonly used, even can reach 200 ℃), utilize under the pressure that self water vapour produces, make the very long reaction times of original needs shorten to dozens of minutes, improve reaction efficiency greatly, can adapt to industrial needs;
2. react completely the productive rate height
Improved the transformation efficiency of reactant, increased a utilization ratio of reactant, reduced the waste situation of raw material in producing, the wastewater and waste materials of generation has seldom reduced the pollution to environment;
3. impurity is few, and sepn process is simple
Avoided in the raw material gadolinium ion to sneak into the toxigenous problem of product, reduced the content of diethylenetriamine pentaacetic acid impurity in the product simultaneously, made degree of purity of production improve greatly, sepn process is simple, reduces solvent-oil ratio, and production process is greenization more.
Embodiment
Embodiment one:
The first step is 1mmol, i.e. 0.363g gadolinium sesquioxide and 2mmol, and promptly 0.787g diethylenetriamine pentaacetic acid mixing joins in the hydrothermal reactor, adds 55mmol, i.e. 1g water.Under 190 ℃ of hydrothermal conditions, heated 15 minutes, take out reactor cooling.
After the solution cooling that the second step the first step makes, filter, evaporate, get crystal, gadolinium-diethylenetriamine pentaacetic acid crude product;
The 3rd step ethyl alcohol recrystallization, vacuum-drying gets the pure product 1.8mmol of gadolinium-diethylenetriamine pentaacetic acid.
Embodiment two:
The first step is 0.1mmol, i.e. 0.0363g gadolinium sesquioxide and 0.2mmol, and promptly 0.0787g diethylenetriamine pentaacetic acid mixing joins in the hydrothermal reactor, adds 55mmol, i.e. 1g water.Under 150 ℃ of hydrothermal conditions, heated 60 minutes, take out reactor cooling.
After the solution cooling that the second step the first step makes, filter, evaporate, get crystal, gadolinium-diethylenetriamine pentaacetic acid crude product;
The 3rd step ethyl alcohol recrystallization, vacuum-drying gets the pure product 0.18mmol of gadolinium-diethylenetriamine pentaacetic acid.
Embodiment three:
The first step is 0.5mmol, i.e. 0.182g gadolinium sesquioxide and 1mmol, and promptly 0.394g diethylenetriamine pentaacetic acid mixing joins in the hydrothermal reactor, adds 110mmol, i.e. 2g water.Under 120 ℃ of hydrothermal conditions, heated 3 hours, take out reactor cooling.
After the solution cooling that the second step the first step makes, filter, evaporate, get crystal, gadolinium-diethylenetriamine pentaacetic acid crude product;
The 3rd step ethyl alcohol recrystallization, vacuum-drying gets the pure product 0.9mmol of gadolinium-diethylenetriamine pentaacetic acid.
Embodiment four:
The first step is 1mmol, i.e. 0.363g gadolinium sesquioxide and 2mmol, and promptly 0.787g diethylenetriamine pentaacetic acid mixing joins in the hydrothermal reactor, adds 28mmol, i.e. 0.5g water.Under 90 ℃ of hydrothermal conditions, heated 8 hours, take out reactor cooling.
After the solution cooling that the second step the first step makes, filter, evaporate, get crystal, gadolinium-diethylenetriamine pentaacetic acid crude product;
The 3rd step ethyl alcohol recrystallization, vacuum-drying gets the pure product 1.8mmol of gadolinium-diethylenetriamine pentaacetic acid.
Claims (1)
1. the method for the synthetic gadolinium-diethylenetriamine pentaacetic acid of hydro-thermal is characterized in that, concrete building-up process:
Behind the first step gadolinium sesquioxide and the diethylenetriamine pentaacetic acid mixing, add in the hydrothermal reactor, add entry again, become suspension liquid, put into 80～200 ℃ of environment following 10 minutes～10 hours, and took out cooling, get gadolinium-diethylenetriamine pentaacetic acid solution, the mol ratio of gadolinium sesquioxide, diethylenetriamine pentaacetic acid and water is 1: 2: (20～600), chemical reaction skeleton symbol: Gd
2O
3+ DTPA---〉Gd (DTPA)+3H
2O;
After the solution cooling that the second step the first step makes, filter, evaporate, get crystal, gadolinium-diethylenetriamine pentaacetic acid crude product;
The 3rd step was used the ordinary method ethyl alcohol recrystallization, and vacuum-drying gets the pure product of gadolinium-diethylenetriamine pentaacetic acid, and the mol ratio of gadolinium sesquioxide and the pure product of gadolinium-diethylenetriamine pentaacetic acid is 1: 1.8.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005100238006A CN1321122C (en) | 2005-02-03 | 2005-02-03 | Water heating synthesis of yttrium-diethyltriamine pentacetate |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2005100238006A CN1321122C (en) | 2005-02-03 | 2005-02-03 | Water heating synthesis of yttrium-diethyltriamine pentacetate |
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| CN1680393A CN1680393A (en) | 2005-10-12 |
| CN1321122C true CN1321122C (en) | 2007-06-13 |
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| CNB2005100238006A Expired - Fee Related CN1321122C (en) | 2005-02-03 | 2005-02-03 | Water heating synthesis of yttrium-diethyltriamine pentacetate |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100364952C (en) * | 2005-12-23 | 2008-01-30 | 华东师范大学 | Process for hydrothermal synthesizing bismuth citrate |
| CN100355723C (en) * | 2006-03-17 | 2007-12-19 | 王润华 | Dimeglumine gadopentetate and its producing method |
| WO2007137418A1 (en) * | 2006-05-27 | 2007-12-06 | Winnik Mitchell A | Polymer backbone element tags |
| CN101912623B (en) * | 2010-08-24 | 2012-06-06 | 上海师范大学 | Preparation and application of Fe-Gd double-mode magnetic resonance contrast agent with targeting function |
| CN107228848B (en) * | 2017-06-16 | 2020-09-08 | 上海市第十人民医院 | Wide fluorescence spectrum and MRI (magnetic resonance imaging) dual-image functional microsphere tracing mesenchymal stem cells and application |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1252051A (en) * | 1997-04-18 | 2000-05-03 | 耐克麦德英梅金公司 | Contrast agent preparation |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1252051A (en) * | 1997-04-18 | 2000-05-03 | 耐克麦德英梅金公司 | Contrast agent preparation |
Non-Patent Citations (5)
| Title |
|---|
| MRI顺磁性造影剂GD-DTPA的合成 李铁福等，化学试剂，第26卷第3期 2004 * |
| MRI顺磁性造影剂GD-DTPA的合成 李铁福等，化学试剂，第26卷第3期 2004;Syntheses and Structure of Nine-Coordinate Gd~ⅢComplexes,Na[Gd~Ⅲ(edta)(H_2O)_3]·5H_2O and Na_4[Gd~Ⅲ(dtpa)(H_2O)]_2·14H_2O 王君等,Journal of Rare Earths,Vol.21 2003;Synthesis and Structural Determination of Nine-coordinateK_2[Y~Ⅲ(dtpa)(H_2O)]·7H_2O 王君等,Rare Metals,Vol.19 No.4 2000;用于磁共振成像对比增强的造影剂研发进展 俞开潮等，波谱学杂志，第21卷第4期 2004 * |
| Syntheses and Structure of Nine-Coordinate Gd~ⅢComplexes,Na[Gd~Ⅲ(edta)(H_2O)_3]·5H_2O and Na_4[Gd~Ⅲ(dtpa)(H_2O)]_2·14H_2O 王君等,Journal of Rare Earths,Vol.21 2003 * |
| Synthesis and Structural Determination of Nine-coordinateK_2[Y~Ⅲ(dtpa)(H_2O)]·7H_2O 王君等,Rare Metals,Vol.19 No.4 2000 * |
| 用于磁共振成像对比增强的造影剂研发进展 俞开潮等，波谱学杂志，第21卷第4期 2004 * |
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