CN109593145B - Cyclic polymer with nuclear magnetic imaging function and preparation method and application thereof - Google Patents
Cyclic polymer with nuclear magnetic imaging function and preparation method and application thereof Download PDFInfo
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- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/085—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier conjugated systems
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- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
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Abstract
The invention discloses a cyclic polymer with a nuclear magnetic imaging function, a preparation method and application thereof, wherein the cyclic polymer with the nuclear magnetic imaging function has the following structural formula:wherein n has a value ranging from 10 to 400 and m is 5 or 6. The invention obtains a ring polymer with magnetic resonance imaging function by means of molecular design, and can be used for magnetic resonance imaging of blood, organs, cells and tumors of a human body. The cyclic polymer has good water solubility, and can be metabolized out of a mouse body in 0.2-12 hours generally.
Description
Technical Field
The invention relates to a water-soluble cyclic polymer, in particular to a cyclic polymer with a nuclear magnetic imaging function and a preparation method and application thereof.
Background
In the seventies of the last century, Maglard, Hutchison, Lauterbour and the like firstly obtained a first historical human body nuclear Magnetic Resonance Image (MRI). With the widespread clinical application of nuclear magnetic resonance, it has gradually become a routine image examination means for many hospitals. Magnetic Resonance Imaging (MRI) is an effective means for tumor detection at present, has the advantages of no trauma, high resolution, no radiation and the like, and particularly has unique advantages compared with other diagnostic means such as CT for the diagnosis of soft tissues. Contrast agents are widely used because they effectively improve MRI imaging accuracy and broaden the diagnostic range, and more than 40% of MRI clinically require contrast agents. The gadolinium micromolecular contrast agent has stable chemical structure, can effectively reduce the biological toxicity of gadolinium ions, and is the MRI contrast agent with the most extensive clinical application. However, gadolinium-containing small molecule contrast agents have the disadvantages of low relaxivity, poor specificity, large dosage and the like, and the multifunctional development of gadolinium-containing contrast agents has become a main development trend. The gadolinium macromolecule contrast agent can effectively overcome the defects of the gadolinium micromolecule contrast agent, so that the gadolinium macromolecule contrast agent draws the attention of the scientists in the fields of material science and biomedicine.
In recent years, Magnetic Resonance Imaging (MRI) has been widely used in clinical diagnosis, and has particular advantages in the detection of cancer and tumors. In order to be able to distinguish the lesion tissue more accurately, a contrast agent is indispensable. At present, low molecular weight gadolinium-containing complexes such as Magnevist, Omniscan and Dotarem are the only clinically used class of MRI contrast agents due to their low toxicity and high stability. However, the contrast agent has the defects of short in vivo circulation time, low relaxation rate, large dosage and the like.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a cyclic polymer with a nuclear magnetic imaging function, and a preparation method and application thereof. The invention obtains a ring polymer with magnetic resonance imaging function by means of molecular design, and can be used for magnetic resonance imaging of blood, organs, cells and tumors of a human body. The cyclic polymer has good water solubility, and can be metabolized out of a mouse body in 0.2-12 hours generally.
The invention relates to a cyclic polymer with a nuclear magnetic angiography function, which has the following structural formula:
wherein n has a value range of 10-400 and m is 5 or 6.
The preparation method of the cyclic polymer with the nuclear magnetic imaging function comprises the steps of firstly synthesizing a linear water-soluble polymer by using DHP resin as a functional initiator and polyethylene glycol methacrylate as a monomer, and then performing an azidation reaction by using the linear water-soluble polymer and sodium azide as raw materials to obtain an azido-containing linear polymer; then, carrying out click reaction on the linear polymer containing azido under the catalysis of cuprous bromide to obtain a water-soluble cyclic polymer fixed on the resin; then the water-soluble cyclic polymer, trifluoroacetic acid and dichloroethane are used as raw materials to carry out a cutting reaction to obtain a cyclic polymer without DHP resin; carrying out esterification reaction on the obtained cyclic polymer without DHP resin and diethyltriaminepentaacetic dianhydride to obtain a cyclic chelating agent; and finally, carrying out chelation reaction by using the annular chelating agent and gadolinium chloride hexahydrate as raw materials to obtain a target product.
The preparation method of the cyclic polymer with the nuclear magnetic imaging function specifically comprises the following steps:
step 1: synthesis of Linear Poly (polyethylene glycol methacrylate) immobilized on DHP resin
Under the protection of nitrogen, adding an initiator A, cuprous bromide, monomer polyethylene glycol methacrylate and an organic solvent into a Schlenk tube, performing three cycles of oil pump pumping, liquid nitrogen freezing and nitrogen gas charging, wherein each cycle is performed for 6-15 times, adding pentamethyl diethylenetriamine after the cycle is finished, heating to 60-100 ℃, stirring for reaction for 10-24 hours, repeatedly washing after the reaction is finished, and drying filter residues in vacuum to obtain the DHP resin-immobilized linear poly (polyethylene glycol methacrylate);
wherein the mol ratio of the initiator A, the pentamethyldiethylenetriamine, the cuprous bromide and the monomer polyethylene glycol methacrylate is 1-10: 1-10: 1-10: 1-400.
The initiator A is C11H18BrNO3The CAS number is 1174531-48-6.
Step 2: azide process
Under the protection of nitrogen, adding the linear poly (polyethylene glycol methacrylate) fixed by the DHP resin, sodium azide and an organic solvent into a two-mouth bottle, heating to 35-55 ℃, stirring for reaction for 12-48 hours, repeatedly washing after the reaction is finished, and drying filter residues in vacuum to obtain the linear poly (polyethylene glycol methacrylate) fixed by the DHP resin;
wherein the mole ratio of the linear poly (polyethylene glycol methacrylate) fixed by the DHP resin to the sodium azide is 1: 1-10.
And step 3: click reaction
Under the protection of nitrogen, adding linear azide poly (polyethylene glycol methacrylate), cuprous bromide and an organic solvent fixed by DHP resin into a Schlenk tube, pumping air by an oil pump, freezing by liquid nitrogen and inflating by nitrogen for three cycles, wherein each cycle is performed for 6-15 times, adding pentamethyl diethylenetriamine after the cycle is finished, heating to 60-100 ℃, stirring for reaction for 10-48 hours, repeatedly washing after the reaction is finished, and drying filter residues in vacuum to obtain cyclic poly (polyethylene glycol methacrylate) fixed by DHP resin;
wherein the mole ratio of cuprous bromide, pentamethyldiethylenetriamine and the linear poly (polyethylene glycol methacrylate) fixed by DHP resin is 1-10: 1-10: 1-10.
And 4, step 4: cleavage reaction
Under the protection of nitrogen, adding cyclic poly (polyethylene glycol methacrylate) fixed by DHP resin, an organic solvent and trifluoroacetic acid into a two-mouth bottle, stirring at room temperature for reaction for 10-48 hours, repeatedly washing with tetrahydrofuran after the reaction is finished, and carrying out rotary drying on the filtrate to obtain cyclic poly (polyethylene glycol methacrylate);
wherein, the molar ratio of trifluoroacetic acid to DHP resin fixed cyclic poly (polyethylene glycol methacrylate) is 1-10: 0.1-10, the volume ratio of the organic solvent to the trifluoroacetic acid is 1: 0.1-1.
And 5: esterification reaction
Under the protection of nitrogen, dissolving cyclic poly (polyethylene glycol methacrylate), diethyltriaminepentaacetic dianhydride, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 4-dimethylaminopyridine in an organic solvent, stirring and reacting for 10-48 hours at room temperature, dialyzing for 12-24 hours by using deionized water after the reaction is finished, and freeze-drying to obtain a product, namely a cyclic chelating agent;
wherein the molar ratio of cyclic poly (polyethylene glycol methacrylate), diethyltriaminepentaacetic dianhydride, 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 4-dimethylaminopyridine is 0.01-0.1: 1-10: 1-10: 0.1-1.
Step 6: chelation reaction
Dissolving a cyclic chelating agent, gadolinium chloride hexahydrate and ammonium acetate in an organic solvent, stirring and reacting for 10-48 hours at room temperature, dialyzing for 48-72 hours by deionized water after the reaction is finished, and freeze-drying to obtain the cyclic contrast agent.
Wherein the molar ratio of the cyclic chelating agent to the gadolinium chloride hexahydrate to the ammonium acetate is 0.01-0.1: 1-10: 0.01-1.
The invention can obtain the cyclic polymer with good water solubility on one hand, and has good contrast effect by introducing gadolinium ions in the cyclic polymer on the other hand.
In step 1, the synthesis process of the hydroxyl-containing linear polymer is as follows:
wherein n has a value range of 10-400 and m is 5 or 6.
The organic solvent is selected from tetrahydrofuran, N' -dimethylformamide, dichloromethane or dioxane, etc.
In step 2, the azidation process is as follows:
wherein n has a value range of 10-400 and m is 5 or 6.
The organic solvent is selected from tetrahydrofuran, N' -dimethylformamide, dichloromethane or dioxane, etc.
In step 3, the click reaction process is as follows:
wherein n has a value range of 10-400 and m is 5 or 6.
The organic solvent is selected from tetrahydrofuran, N' -dimethylformamide, dichloromethane or dioxane, etc.
In step 4, the cleavage reaction process is as follows:
wherein n has a value range of 10-400 and m is 5 or 6.
The organic solvent is selected from dichloromethane, tetrahydrofuran or dioxane, etc.
In step 5, the esterification reaction process is as follows:
wherein n has a value range of 10-400 and m is 5 or 6.
The organic solvent is selected from deionized water, tetrahydrofuran, N' -dimethylformamide or dioxane, etc.
In step 6, the chelation reaction process is as follows:
wherein n has a value range of 10-400 and m is 5 or 6.
The organic solvent is selected from deionized water, tetrahydrofuran, N' -dimethylformamide or dioxane, etc.
The application of the cyclic polymer is to prepare a solution with a certain concentration of the cyclic polymer to be used as a contrast agent for magnetic resonance imaging.
The cyclic polymer with the nuclear magnetic imaging function has good water solubility, and the gadolinium ion concentration of the solution is 0.05-2mg/mL, and the solution can be completely metabolized within 0.2-12 hours generally.
The cyclic polymer with the nuclear magnetic imaging function is simple to prepare, the used materials are environment-friendly, and the cyclic polymer has great potential application value in the field of biological medical treatment.
Compared with the prior art, the invention has the beneficial effects that:
1. the linear polymer is designed by an atom transfer radical polymerization (ATRP polymerization) method, and the linear polymer prepared by the method has controllable molecular weight and inherits the excellent water-solubility performance of the polyethylene glycol methacrylate.
2. The invention adopts atom transfer radical polymerization, has simple and efficient reaction process, simple post-treatment, controllable reaction conditions and good repeatability, and is easy to realize industrial production.
3. The invention combines the polymer and gadolinium ions, and compared with a simple polymer or gadolinium particles, the contrast agent prepared by the invention can be stably distributed and exist in water, has the characteristics of low toxicity and environmental friendliness, and is expected to be widely applied in clinical aspects.
Drawings
FIG. 1 shows the infrared spectra before and after the change from bromo group to azido group in the cyclic polymer, and it can be seen from FIG. 1 that the cyclic polymer containing azido group is 2100cm-1The peak of bromine group is shown, and it can be seen that the product obtained by click is a cyclic polymer containing azide groups.
FIG. 2 is a graph showing a particle size distribution of the resulting cyclic polymer in Dynamic Light Scattering (DLS). As can be seen from FIG. 2, the water-soluble cyclic polymer has a good particle size distribution with a size of about 220 nm.
FIG. 3 is a graph of the star relaxivity of the resulting cyclic polymers. As can be seen in FIG. 3, the measured relaxation rate is r1=12.3mM-1S-1
Detailed Description
The present invention will be described in further detail with reference to specific examples. It should be understood that the following examples are illustrative of the present invention only and are not intended to limit the scope of the present invention.
Example 1:
1. under the protection of nitrogen, 1g (0.01mmol) of the initiator A synthesized in the laboratory, 1.43mg (0.01mmol) of cuprous bromide and 0.36g (1mmol) of the monomer (polyethylene glycol methacrylate) are added into a Schlenk tube, 10mLN, N' -dimethylformamide is added as a solvent, and three cycles of air suction, freezing and air inflation are carried out for 10 times in each cycle. After circulation, 1.73mg (0.01mmol) pentamethyldiethylenetriamine is added, the temperature is raised to 70 ℃, stirring is carried out for reaction for 12 hours, repeated washing is carried out after the reaction is finished, and the filter residue is dried in vacuum to obtain the linear poly-oligo-polyethylene glycol methacrylate fixed with DHP resin, wherein the yield is 83.3%.
2. Under the protection of nitrogen, taking 1.30g of the linear poly (polyethylene glycol methacrylate) for fixing and DHP resin prepared in the step 1 as a raw material, adding 65mg (1mmol) of sodium azide into a double-mouth bottle with a double-row pipe and a stirring magneton, adding 10mLN, N' -dimethylformamide as a solvent, heating to 35 ℃, stirring for reaction for 12 hours, repeatedly washing after the reaction is finished, and drying filter residues in vacuum to obtain the linear poly (oligo-ethylene glycol methacrylate) for fixing and DHP resin with the yield of 98%.
3. Under the protection of nitrogen, 1.28g of the linear poly (polyethylene glycol methacrylate) fixed with DHP resin prepared in the step 2 is taken as a raw material, 1.43mg (0.01mmol) of the linear poly (polyethylene glycol methacrylate) fixed with DHP resin is added into a Schlenk tube provided with double rows of tubes and stirring magnetons, 10mLN, N' -dimethylformamide is added as a solvent, three cycles of oil pump pumping, liquid nitrogen freezing and nitrogen gas charging are carried out, 10 times of each cycle are carried out, after the cycle is finished, 1.73mg (0.01mmol) of pentamethyldiethylenetriamine is added, the temperature is raised to 70 ℃, stirring reaction is carried out for 12 hours, repeated washing is carried out after the reaction is finished, and the filter residue is dried in vacuum to obtain the cyclic poly (polyethylene glycol methacrylate) fixed with DHP resin.
4. Under the protection of nitrogen, 1.28g of the cyclic poly (polyethylene glycol methacrylate) fixed with DHP resin prepared in the step 3 is used as a raw material, 10mL of dichloromethane and 1mL of trifluoroacetic acid are added into a two-necked bottle provided with a double-row pipe and a stirring magneton, the mixture is stirred and reacted for 12 hours, after the reaction is finished, tetrahydrofuran is used for repeatedly washing, and the filtrate is subjected to rotary drying to obtain the cyclic poly (polyethylene glycol methacrylate), wherein the yield is 89.3%.
5. Under the protection of nitrogen, 0.25g of cyclic poly (polyethylene glycol methacrylate) prepared in the step 4 is taken as a raw material, 0.357g (1mmol) of diethyltriamine pentaacetic acid dianhydride, 10mL of deionized water, 0.192g (1mmol) of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 0.122g (1mmol) of 4-dimethylaminopyridine are added into a two-necked bottle with a double-row pipe and a stirring magnet, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the deionized water is dialyzed for 12 hours, and the cyclic chelating agent is obtained by freeze drying, wherein the yield is about 69%.
6. Under the protection of nitrogen, 0.42g of the cyclic chelating agent prepared in the step 5 is used as a raw material, 0.37g (1mmol) of gadolinium chloride hexahydrate, 100mL of deionized water and 77mg (0.1mmol) of ammonium acetate are added into a two-port bottle provided with a double-row pipe and a stirring magneton, stirring reaction is carried out for 12 hours, deionized water dialysis is carried out for 48 hours after the reaction is finished, and freeze drying is carried out to obtain the cyclic contrast agent, wherein the yield is 73.6%.
Example 2:
1. under the protection of nitrogen, 2g (0.02mmol) of the initiator A synthesized in the laboratory, 1.43mg (0.01mmol) of cuprous bromide and 0.36g (1mmol) of the monomer (polyethylene glycol methacrylate) are added into a Schlenk tube, 10mLN, N' -dimethylformamide is added as a solvent, and three cycles of air suction, freezing and air inflation are carried out for 15 times in each cycle. After circulation, 1.73mg (0.01mmol) pentamethyldiethylenetriamine is added, the temperature is raised to 80 ℃, stirring is carried out for reaction for 24 hours, repeated washing is carried out after the reaction is finished, and filter residue is dried in vacuum to obtain the linear poly (polyethylene glycol methacrylate) fixed with the DHP resin, wherein the yield is 82.4%.
2. Under the protection of nitrogen, taking 2.30g of the linear poly (polyethylene glycol methacrylate) for fixing and DHP resin prepared in the step 1 as a raw material, adding 65mg (1mmol) of sodium azide into a double-mouth bottle with a double-row pipe and a stirring magneton, adding 20mLN, N' -dimethylformamide as a solvent, heating to 55 ℃, stirring for reaction for 24 hours, repeatedly washing after the reaction is finished, and drying filter residues in vacuum to obtain the linear poly (polyethylene glycol methacrylate) for fixing and DHP resin with the yield of 98%.
3. Under the protection of nitrogen, 1.28g of the linear poly (polyethylene glycol methacrylate) fixed with the DHP resin prepared in the step 2 is used as a raw material, 1.43mg (0.01mmo) of the linear poly (polyethylene glycol methacrylate) fixed with the DHP resin is added into a Schlenk tube provided with double rows of tubes and stirring magnetons, 20mLN, N' -dimethylformamide is added to be used as a solvent, three cycles of oil pump pumping, liquid nitrogen freezing and nitrogen gas charging are carried out, each cycle is carried out for 15 times, after the cycle is finished, 1.73mg (0.01mmol) of pentamethyldiethylenetriamine is added, the temperature is raised to 80 ℃, stirring is carried out for reaction for 24 hours, repeated washing is carried out after the reaction is finished, and the filter residue is dried in vacuum to obtain the cyclic poly (polyethylene glycol methacrylate).
4. Under the protection of nitrogen, 2.28g of the cyclic poly (polyethylene glycol methacrylate) fixed with DHP resin prepared in the step 3 is used as a raw material, 10mL of dichloromethane and 1mL of trifluoroacetic acid are added into a two-mouth bottle provided with a double-row pipe and a stirring magneton, stirring reaction is carried out for 24 hours, washing is repeatedly carried out by tetrahydrofuran after the reaction is finished, and the filtrate is dried in a rotating mode to obtain the cyclic poly (polyethylene glycol methacrylate), wherein the yield is 89.3%.
5. Under the protection of nitrogen, 0.26g of cyclic poly (polyethylene glycol methacrylate) prepared in the step 4 is taken as a raw material, 0.357g (1mmol) of diethyltriamine pentaacetic acid dianhydride, 20mL of deionized water, 0.192g (1mmol) of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 0.122g (1mmol) of 4-dimethylaminopyridine are added into a two-necked bottle with a double-row pipe and a stirring magnet, the mixture is stirred and reacted for 24 hours, and after the reaction is finished, the deionized water is dialyzed for 24 hours, and the cyclic chelating agent is obtained by freeze drying, wherein the yield is about 72%.
6. Under the protection of nitrogen, 0.42g of the cyclic chelating agent prepared in the step 5 is used as a raw material, 0.44g (1mmol) of gadolinium chloride hexahydrate, 200mL of deionized water and 77mg (0.1mmol) of ammonium acetate are added into a two-port bottle provided with a double-row pipe and a stirring magneton, stirring reaction is carried out for 24 hours, deionized water dialysis is carried out for 72 hours after the reaction is finished, and freeze drying is carried out to obtain the cyclic contrast agent, wherein the yield is 70.6%.
Example 3:
1. under the protection of nitrogen, 3g (0.03mmol) of initiator A synthesized in the laboratory, 1.43mg (0.01mmol) of cuprous bromide and 0.36g (1mmol) of monomer (polyethylene glycol methacrylate) are added into a Schlenk tube, 10mLN, N' -dimethylformamide is added as a solvent, and three cycles of air suction, freezing and air inflation are carried out for 10 times in each cycle. After circulation, 1.73mg (0.01mmol) pentamethyldiethylenetriamine is added, the temperature is raised to 70 ℃, stirring is carried out for reaction for 12 hours, repeated washing is carried out after the reaction is finished, and the filter residue is dried in vacuum to obtain the linear poly (polyethylene glycol methacrylate) fixed with the DHP resin, wherein the yield is 80.3%.
2. Under the protection of nitrogen, taking 2.30g of the linear poly (polyethylene glycol methacrylate) for fixing and DHP resin prepared in the step 1 as a raw material, adding 65mg (1mmol) of sodium azide into a double-mouth bottle with a double-row pipe and a stirring magneton, adding 10mLN, N' -dimethylformamide as a solvent, heating to 35 ℃, stirring for reaction for 12 hours, repeatedly washing after the reaction is finished, and drying filter residues in vacuum to obtain the linear poly (polyethylene glycol methacrylate) for fixing and DHP resin with the yield of 90.8%.
3. Under the protection of nitrogen, 3.28g of the linear poly (polyethylene glycol methacrylate) fixed with the DHP resin prepared in the step 2 is used as a raw material, 1.43mg (0.01mmol) of the linear poly (polyethylene glycol methacrylate) fixed with the DHP resin is added into a Schlenk tube provided with double rows of tubes and stirring magnetons, 10mLN, N' -dimethylformamide is added to be used as a solvent, three cycles of pumping by an oil pump, freezing by liquid nitrogen and inflating by nitrogen are carried out for 10 times, after the cycle is finished, 1.73mg (0.01mmol) of pentamethyldiethylenetriamine is added, the temperature is raised to 70 ℃, stirring is carried out for reaction for 12 hours, repeated washing is carried out after the reaction is finished, and the filter residue is dried in vacuum to obtain the cyclic poly (polyethylene glycol methacrylate) fixed with the.
4. Under the protection of nitrogen, 2.28g of the cyclic poly (polyethylene glycol methacrylate) fixed with DHP resin prepared in the step 3 is used as a raw material, 10mL of dichloromethane and 1mL of trifluoroacetic acid are added into a two-necked bottle provided with a double-row pipe and a stirring magneton, the mixture is stirred and reacted for 12 hours, after the reaction is finished, tetrahydrofuran is used for repeatedly washing, and the filtrate is subjected to rotary drying to obtain the cyclic poly (polyethylene glycol methacrylate), wherein the yield is 96.4%.
5. Under the protection of nitrogen, 0.27g of cyclic poly (polyethylene glycol methacrylate) prepared in the step 4 is taken as a raw material, 0.357g (1mmol) of diethyltriamine pentaacetic acid dianhydride, 10mL of deionized water, 0.192g (1mmol) of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and 0.122g (1mmol) of 4-dimethylaminopyridine are added into a two-necked bottle with a double-row pipe and a stirring magnet, the mixture is stirred and reacted for 12 hours, after the reaction is finished, the deionized water is dialyzed for 12 hours, and the cyclic chelating agent is obtained by freeze drying, wherein the yield is about 86.1%.
6. Under the protection of nitrogen, 0.54g of the cyclic chelating agent prepared in the step 5 is used as a raw material, 0.37g (1mmol) of gadolinium chloride hexahydrate, 100mL of deionized water and 77mg (0.1mmol) of ammonium acetate are added into a two-port bottle provided with a double-row pipe and a stirring magneton, stirring reaction is carried out for 12 hours, deionized water dialysis is carried out for 48 hours after the reaction is finished, and freeze drying is carried out to obtain the cyclic contrast agent, wherein the yield is 60.1%.
It should be noted that the above conditions can be arbitrarily combined to obtain the preferred embodiment of the present invention on the basis of the common general knowledge in the field.
Claims (3)
2. A method for producing the cyclic polymer according to claim 1, characterized in that: DHP resin is used as a functional initiator, polyethylene glycol methacrylate is used as a monomer, a linear water-soluble polymer is firstly synthesized, and then the linear water-soluble polymer and sodium azide are used as raw materials to carry out an azide reaction to obtain an azide-containing linear polymer; then, carrying out click reaction on the linear polymer containing azido under the catalysis of cuprous bromide to obtain a water-soluble cyclic polymer fixed on the resin; then the water-soluble cyclic polymer, trifluoroacetic acid and dichloroethane are used as raw materials to carry out a cutting reaction to obtain a cyclic polymer without DHP resin; carrying out esterification reaction on the obtained cyclic polymer without DHP resin and diethyltriaminepentaacetic dianhydride to obtain a cyclic chelating agent; finally, carrying out chelation reaction by taking the annular chelating agent and gadolinium chloride hexahydrate as raw materials to obtain a target product;
the structure of the functionalized initiator is shown as follows:
3. use of a cyclic polymer according to claim 1, wherein: the cyclic polymer is prepared into a solution with a certain concentration to be used as a contrast agent for magnetic resonance imaging, and the concentration of gadolinium ions in the solution is 0.05-2 mg/mL.
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