Paramagnetic metal complex using aspartic acid-isoleucine copolymer as carrier, preparation method of paramagnetic metal complex and magnetic resonance imaging contrast agent
A technology of isoleucine copolymer and aspartic acid, which is applied in preparations for in vivo experiments and pharmaceutical formulations, can solve the problems of low contrast agent liver recognition, short imaging time, and low relaxation efficiency. Achieve good water solubility, long imaging time and high relaxation efficiency
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[0040] The present invention also provides a method for preparing a paramagnetic metal complex with an aspartic acid-isoleucine copolymer as a carrier, comprising the following steps:
[0041] Step 1: preparing aspartic acid-isoleucine copolymer;
[0042] Step 2: reacting the aspartic acid-isoleucine copolymer obtained in step 1 with ethylenediamine to obtain an aminated aspartic acid-isoleucine copolymer;
[0043] Step 3: react the aminated aspartic acid-isoleucine copolymer obtained in step 2 with DOTA mono-N-hydroxyl sulfosuccinimide active ester to obtain aspartic acid-isoleucine 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macromolecule ligand with copolymer as carrier;
[0044]Step 4: The 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid obtained in step 3 with aspartic acid-isoleucine copolymer as a carrier The molecular ligand reacts with the aqueous solution containing paramagnetic metal ions to obtain the paramagnetic metal complex with the aspar...
Embodiment 1
[0062] Preparation of Aspartic Acid-Isoleucine Copolymers Modified by Ethylenediamine 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Gadolinium Tetraacetate Complexes
[0063] (1) Mix 20 grams of L-aspartic acid with 5 grams of L-isoleucine, add 8 grams of the mixed mixture into a phosphoric acid solution with a mass fraction of 85%, and stir evenly. (24mmHg) for 5 hours, the reaction temperature was controlled at 165°C, precipitated with deionized water, filtered, washed, and dried under reduced pressure to obtain an aspartic acid-isoleucine copolymer;
[0064] (2) Dissolve the aspartic acid-isoleucine copolymer synthesized in (1) in N,N-dimethylformamide solution at room temperature, and add ethylenediamine and ethylenediamine dropwise while stirring. The mass ratio of amine to aspartic acid-isoleucine copolymer was 2.8:1, stirred at room temperature for 4 hours, precipitated with ether, filtered, dialyzed, and freeze-dried to obtain aminated aspartic acid-isoleucine copolymer thi...
Embodiment 2
[0069] Preparation of Aspartic Acid-Isoleucine Copolymers Modified by Ethylenediamine 1,4,7,10-Tetraazacyclododecane-1,4,7,10-Gadolinium Tetraacetate Complexes
[0070] (1) Mix 20 grams of L-aspartic acid with 2 grams of L-isoleucine, add 8 grams of the mixed mixture into a phosphoric acid solution with a mass fraction of 85%, and stir evenly. (100mmHg) for 1 hour, the reaction temperature was controlled at 220°C, precipitated with deionized water, filtered, washed, and dried under reduced pressure to obtain an aspartic acid-isoleucine copolymer;
[0071] (2) with step (2) in embodiment 1;
[0072] (3) with step (3) in embodiment 1;
[0073] (4) Same as step (4) in Example 1.
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Abstract
Description
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Application Information
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