CN105288667B - A kind of ultrasound/magnetic resonance dual-mode contrast medium and preparation method and application - Google Patents
A kind of ultrasound/magnetic resonance dual-mode contrast medium and preparation method and application Download PDFInfo
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Abstract
The present invention relates to a kind of ultrasound/magnetic resonance dual-mode contrast medium and preparation method and application, contrast agent is that surface uses polyvinyl pyrrolidon modified coordination polymer nanoparticle contrast agent, there is cavity structure inside the coordination polymer nanoparticle contrast agent, and also doped with rare earth element Ir and Ho in described coordination polymer nanoparticle contrast agent；During preparation, the DMSO solution of the bipyridyl dicarboxylic acids complex of iridium of 2 phenylchinoline 3,3 ' is prepared, add polyvinylpyrrolidone, it is uniformly mixed, and is warming up to 30 200 DEG C, the 2h of constant temperature 0.1, add the DMSO solution of acetic acid holmium, 0.1 48h is reacted, after reaction terminates, with 10 12h of deionized water dialysis, centrifugation, you can；Obtained dual-mode contrast medium is used for ultrasonic contrast imaging and magnetic resonance radiography is imaged.Compared with prior art, dual-mode contrast medium pattern of the present invention is homogeneous, and good dispersion, excellent in stability, synthesis technique is simple, and raw material is easy to get, environmentally safe, has good application prospect.
Description
Technical field
The invention belongs to medical imaging technology field, is related to a kind of ultrasound/magnetic resonance dual-mode contrast medium and its preparation side
Method and application.
Background technology
Molecular imaging is the subject that Medical Imaging Technology and molecular biology combine, and the subject can be with using Image-forming instrument
Obtain the Pathological Information of body early stage.In numerous iconographies, ultrasonic imaging medical treatment cost is low, and it is any can to obtain body tissue
The image of tomography, have the characteristics that imaging is fast, organ movement is visible, diagnosis is timely, no pain, with not dangerous property, non-
It is damaging；And Magnetic resonance imaging, then because it can carry out multi-parameter imaging, there is provided diagnostic message is enriched, fast and safely, focus
Compare substantially, thus be used widely with normal portions.
Ultrasonic imaging is in difference acoustically, with waveform, curve and figure using ultrasonic wave physical characteristic and human organ
The form of picture has medically obtained extensively in the deagnostic test for carrying out disease, ultrasonic imaging to embody the difference of body
General application.Magnetic resonance imaging is mainly produced different using organism different tissues reclaimed water Molecular Mass under externally-applied magnetic field image
Resonance signal (signal strength depend on tissue in the content of water and the relaxation time of water proton) is imaged.But for lesions position
Focus radiography is not obvious enough, and simple ultrasonic or NMR imaging is unable to reach the confirmation of pathological tissues, causes the possibility of mistaken diagnosis
Improve.
In ultrasonic imaging and magnetic resonance imaging application aspect, the presence of contrast agent can preferably make up lesion tissue radiography
The problem of resolution ratio is low.For example, acoustic contrast agent is usually the material with cavity structure, and for the ease of being followed in later stage body
Ring, scantling is unsuitable excessive, in order to there is more preferable ultrasonic effect, in the case that other conditions are consistent (such as normal body-internal-circulation,
Scattering, the rate of decay and cyclic process do not rupture), when scantling is fixed, cavity is bigger, more has to imaging effect
Profit；The presence of NMR imaging contrast agent also can more effectively increase focus and normal structure contrast, so as to be advantageous to more early stage,
The discovery of the focus of deeper.
However, at present in terms of the research of contrast agent, contrast agent used in existing clinic is only used for a kind of image
Section is learned to do to check, and the research for the contrast agent for being used for magnetic resonance radiography for that can be used for ultrasonic contrast and can is very few, this nothing
Doubt the development of meeting limit multimode formula shadowgraph technique.Therefore, research and develop a kind of dual-mode contrast medium, can be used for ultrasonic contrast and
Magnetic resonance radiography, then it is particularly important.
The Chinese invention patent of Application No. 201410600719.9 discloses a kind of ultrasound/magnetic resonance bimodal radiography
Agent, its preparation method and application, described bimodal contrast agent is using the nanoparticle suspension of nuclear magnetic resonance imaging as raw material, warp
Hollow ball shape nanometer particle congery, the bimodulus that structure ultrasound/magnetic resonance developing function rolls into one is made in drying process with atomizing
State contrast agent, wherein, the nano-particle of nuclear magnetic resonance imaging is superparamagnetic iron oxide nano-particle, superparamagnetic manganese oxide nanoparticle
One or more of compositions in son, cobalt ferrite magnetic nano-particle, Manganese Ferrite magnetic nano-particle, and nuclear magnetic resonance shows
The nano-particle of shadow is core shell structure；The core is superparamagnetic iron oxide nano-particle, superparamagnetic manganese oxide nanoparticle, ferrous acid
One kind in cobalt magnetic nano-particle, Manganese Ferrite magnetic nano-particle, shell are silica.
The present invention has following advantages compared to above-mentioned contrast patent document：
1) in the technical scheme for contrasting patent document, the nano-particle of nuclear magnetic resonance imaging is synthesized first, then is sprayed
Processing, and then hollow material is obtained, and compared with contrasting patent document, technical solution of the present invention is simple, using one-step method
Obtain hollow nano-material；
2) when contrasting patent document to being handled after the nano-particle spraying of nuclear magnetic resonance imaging, parameter influences on product
It is very big, the structural form of product can be directly determined, if parameter selection is improper, hollow sphere nano-particle can not be prepared
Aggregation, it is impossible to as ultrasound/magnetic resonance bimodal contrast agent, and the hollow nano-material Stability Analysis of Structures that the present invention obtains, after
Processing will not have an impact to the form of product；
3) synthesis step of technical solution of the present invention is more simple, synthesizes obtained nano material, stable performance, not by rear
The influence of processing parameter, when being imaged for ultrasound/magnetic resonance bimodal, duration length, it can repeat to be imaged.
The content of the invention
There is excellent water it is an object of the present invention to overcome the above-mentioned drawbacks of the prior art and provide a kind of
Dissolubility and biocompatibility, have concurrently ultrasonic imaging and Magnetic resonance imaging function ultrasound/magnetic resonance dual-mode contrast medium and its
Preparation method and application, by means of existing medical means, conveniently and efficiently make a definite diagnosis focus, reduce misdiagnosis rate, for controlling for lesion
Treatment provides safeguard.
The purpose of the present invention can be achieved through the following technical solutions：
A kind of ultrasound/magnetic resonance dual-mode contrast medium, the contrast agent are that surface is matched somebody with somebody using polyvinyl pyrrolidon modified
Position polymer nano-particle contrast agent, coordination polymer nanoparticle contrast agent inside have cavity structure, and described
Also doped with rare earth element Ir and Ho in coordination polymer nanoparticle contrast agent.
The chemical structural formula of described coordination polymer nanoparticle contrast agent is：
In described coordination polymer nanoparticle contrast agent, rare earth element Ir weight/mass percentage composition is 2-40%, dilute
Earth elements Ho weight/mass percentage composition is 1-30%.
The particle diameter (referring to external diameter) of described coordination polymer nanoparticle contrast agent is 100-800nm, wall thickness 20-
100nm。
A kind of preparation method of ultrasound/magnetic resonance dual-mode contrast medium, this method specifically include following steps：
(1) DMSO solution of 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium is prepared；
(2) DMSO solution of acetic acid holmium is prepared；
(3) polyvinylpyrrolidone is added into the solution of step (1), is uniformly mixed, and be warming up to 30-200 DEG C,
Constant temperature 0.1-2h；
(4) add step (2) preparation acetic acid holmium DMSO solution, react 0.1-48h, reaction terminate after, spend from
Sub- water dialysis 10-12h, centrifugation, that is, is made described dual-mode contrast medium.
The mass concentration of 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium described in step (1) is 0.01-
10mg/mL。
The mass concentration of acetic acid holmium described in step (2) is 0.01-10mg/mL.
Described 2- phenylchinolines 3,3 '-bipyridyl dicarboxylic acids complex of iridium and polyvinylpyrrolidone, the matter of acetic acid holmium
Measuring ratio is：0.001-500：0.1-50：0.001-500.
A kind of application of ultrasound/magnetic resonance dual-mode contrast medium, described dual-mode contrast medium are used for ultrasonic contrast imaging
And magnetic resonance radiography imaging.
In the present invention, described 2- phenylchinolines 3, the synthetic method of 3 '-bipyridyl dicarboxylic acids complex of iridium is as follows：
Weigh 2- phenylchinoline iridium dichloro bridge complexs (0.1-5g) and 2,2 '-bipyridyl -3,3 '-dicarboxylic acids (0.2-
10g) it is placed in 100mL three-neck flask, in N2Under protection, 5-60 minutes are vacuumized, fill N2About 10-60 minutes；Add 5-15mL
CH2Cl2With 5-15mL CH3OH, back flow reaction 6-24 hours obtain red solution；After reaction terminates, filter, use CH2Cl2With
CH3After OH washings, dry；Use CH2Cl2/CH3OH(10：1, v/v) silicagel column is crossed, you can described 2- phenylchinolines 3 are made,
3 '-bipyridyl dicarboxylic acids complex of iridium.
In the present invention, 2- phenylchinolines 3,3 '-bipyridyl dicarboxylic acids complex of iridium, polyvinylpyrrolidone and acetic acid holmium this
It is that water miscible coordination polymer nano-particle is made by Coordinate self-assembly one-step synthesis method, chemistry is anti-between three kinds of materials
Answer formula as follows：
Polyvinylpyrrolidone is (referred to as：PVP) it is a kind of water-soluble high-molecular compound, there is water soluble polymer chemical combination
The general aspects of thing：Colloid protective effect, film forming, caking property, hygroscopicity, solubilising or cohesion, but its is most characteristic simultaneously
It is its excellent solubility property and physiological compatibility by the property that people pay much attention to.In macromolecule is synthesized as PVP
Both water is dissolved in, it is actually rare to be dissolved in that most of organic solvent, toxicity are very low, physiology intermiscibility is good again, particularly in medicine, food
In these fields closely related with health of people of product, cosmetics, with the reduction of its raw material butyrolactone price, it will be shown
The good prospect of development.From the viewpoint of biology, PVP molecular structure characteristic is similar to simple protein model
Mating capability to some small molecules of that structure, even it water-soluble and can be by the precipitating reagent sulphur of some protein
Sour ammonium, trichloroacetic acid, tannic acid and phenols the characteristic such as precipitate and also mixed with protein, so that being widely used as PVP
The auxiliary material of pharmaceutical preparation.
The size of cavity structure inside dual-mode contrast medium of the present invention, it can be adjusted by changing the reaction time,
With the extension of time, the cavity volume of nano material can become larger.Dual-mode contrast medium internal cavities produced by the present invention
The volume of structure typically constitutes from the 20-80% of nano-particle cumulative volume.
When dual-mode contrast medium produced by the present invention is used for magnetic resonance imaging imaging, the imaging parameters under related magnetic field
Condition is as follows：TR/TE values are 1500/15.6 millisecond, and matrix is 256 × 320, spectral bandwidth 300.3Hz/Px, and thickness degree is 1
Millimeter.During for ultrasonic contrast imaging, related imaging parameters condition is as follows：Sample is in ultrasonic medical instrument (MyLab
Twice；Esaote SpA, Genova, Italy) B-mode is lower surveys and obtain, and its centre frequency is 13MHz and 22MHz.
Compared with prior art, the present invention has synthesized a kind of complex nano-particle, the nanoparticle using simple method
Son has more prominent hollow-core construction, and its pattern is homogeneous, good dispersion, excellent in stability, due to the complex nano-particle
In include metal Ho, this makes it have certain relaxation rate, and good T is shown under nuclear-magnetism angiographic instrument2Imaging effect；Separately
Outside, on material structure, because it has a more prominent hollow-core construction, ultrasonic imaging effect is also clearly.The present invention makes
Shadow agent has been provided simultaneously with the function of Magnetic resonance imaging and ultrasonic imaging, can be used as a kind of potential nuclear-magnetism, the double contrast agent of ultrasound,
Synthesis technique is simple, and raw material is easy to get, environmentally safe, has good application prospect.
Brief description of the drawings
Fig. 1 is the ESEM collection of illustrative plates that embodiment 1 prepares gained dual-mode contrast medium；
Fig. 2 is the transmission electron microscope collection of illustrative plates that embodiment 1 prepares gained dual-mode contrast medium；
Fig. 3 be embodiment 1 prepare gained dual-mode contrast medium under various concentrations ultrasonic contrast imaging figure (wherein, a,
B, concentration corresponding to c, d, e difference is 0 μ g/mL, 100 μ g/mL, 200 μ g/mL, 400 μ g/mL, 600 μ g/mL)；
Fig. 4 is that embodiment 1 prepares magnetic resonance imaging image of the gained dual-mode contrast medium under various concentrations.
Embodiment
The present invention is described in detail with specific embodiment below in conjunction with the accompanying drawings.
Embodiment 1：
Prepare the DMSO solution and 0.3mg/mL of 0.3mg/mL 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium
Acetic acid holmium DMSO solution, it is stand-by.Take 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium that 2mL configured
DMSO solution is placed in single-necked flask, and adds 10mg polyvinylpyrrolidones (PVP K30), after being well mixed, is heated up
To 50 DEG C, constant temperature 0.1h, then the above-mentioned acetic acid holmium solution of 2mL is taken into flask, react 0.25h.After reaction terminates, deionized water is used
Dialyse 12h, then centrifuge washing 3 times, by obtained sample dispersion in deionized water, carries out ultrasound and nuclear magnetic resonance test.
Fig. 1 is the ESEM collection of illustrative plates of dual-mode contrast medium made from the present embodiment, and as can be seen from Figure, described makes
Shadow agent is spheric granules, and good dispersion, soilless sticking phenomenon.
Fig. 2 is the transmission electron microscope collection of illustrative plates of dual-mode contrast medium made from the present embodiment, and as can be seen from Figure, described matches somebody with somebody
The particle diameter of position polymer nano-particle contrast agent is 100-800nm, wall thickness 20-100nm.
Fig. 3 is the transmission electron microscope collection of illustrative plates of dual-mode contrast medium made from the present embodiment, and as can be seen from Figure, described matches somebody with somebody
Position polymer nano-particle contrast agent is because it has a more prominent hollow-core construction, and ultrasonic imaging effect is also clearly.
Fig. 4 is the transmission electron microscope collection of illustrative plates of dual-mode contrast medium made from the present embodiment, and as can be seen from Figure, described matches somebody with somebody
Position polymer nano-particle contrast agent, due to including metal Ho in the complex nano-particle, this makes it have certain relaxation
Henan rate, good T is shown under nuclear-magnetism angiographic instrument2Imaging effect.
Embodiment 2：
Prepare the DMSO solution and 0.7mg/mL of 0.5mg/mL 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium
Acetic acid holmium DMSO solution, it is stand-by.Take 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium that 2mL configured
DMSO solution is placed in single-necked flask, and adds 20mg polyvinylpyrrolidones (PVP K30), after being well mixed, is heated up
To 70 DEG C, constant temperature 0.2h, then the above-mentioned acetic acid holmium solution of 2mL is taken into flask, react 0.5h.After reaction terminates, deionized water is used
Dialyse 12h, then centrifuge washing 3 times, by obtained sample dispersion in deionized water, carries out ultrasound and nuclear magnetic resonance test.
Embodiment 3：
Prepare the DMSO solution and 0.9mg/mL of 0.5mg/mL 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium
Acetic acid holmium DMSO solution, it is stand-by.Take 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium that 5mL configured
DMSO solution is placed in single-necked flask, and adds 30mg polyvinylpyrrolidones (PVP K30), after being well mixed, is heated up
To 70 DEG C, constant temperature 0.3h, then the above-mentioned acetic acid holmium solution of 2mL is taken into flask, react 1h.It is saturating with deionized water after reaction terminates
12h, then centrifuge washing 3 times are analysed, by obtained sample dispersion in deionized water, carries out ultrasound and nuclear magnetic resonance test.
Embodiment 4：
Prepare the DMSO solution and 0.9mg/mL of 0.7mg/mL 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium
Acetic acid holmium DMSO solution, it is stand-by.Take 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium that 5mL configured
DMSO solution is placed in single-necked flask, and adds 30mg polyvinylpyrrolidones (PVP K30), after being well mixed, is heated up
To 90 DEG C, constant temperature 0.3h, then the above-mentioned acetic acid holmium solution of 2mL is taken into flask, react 2h.It is saturating with deionized water after reaction terminates
12h, then centrifuge washing 3 times are analysed, by obtained sample dispersion in deionized water, carries out ultrasound and nuclear magnetic resonance test.
Embodiment 5：
Prepare the 5mg/mL DMSO solution of 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium and 5mg/mL vinegar
The DMSO solution of sour holmium, it is stand-by.Take the DMSO for 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium that 10mL configured molten
Liquid is placed in single-necked flask, and adds 40mg polyvinylpyrrolidones (PVP K30), after being well mixed, is warming up to 90 DEG C,
Constant temperature 1h, then the above-mentioned acetic acid holmium solution of 10mL is taken into flask, react 10h.Reaction terminate after, with deionized water dialyse 12h, then
Centrifuge washing 3 times, by obtained sample dispersion in deionized water, carry out ultrasound and nuclear magnetic resonance test.
Embodiment 6：
The present embodiment ultrasound/magnetic resonance dual-mode contrast medium, the contrast agent are surface using polyvinyl pyrrolidon modified
Coordination polymer nanoparticle contrast agent, there is cavity structure, and institute inside the coordination polymer nanoparticle contrast agent
Also doped with rare earth element Ir and Ho in the coordination polymer nanoparticle contrast agent stated.
Wherein, the chemical structural formula of coordination polymer nanoparticle contrast agent is：
In the present embodiment, in coordination polymer nanoparticle contrast agent, rare earth element Ir weight/mass percentage composition is 40%,
Rare earth element Ho weight/mass percentage composition is 30%.The particle diameter of coordination polymer nanoparticle contrast agent is 800nm, and wall thickness is
100nm。
Preparation method specifically includes following steps：
(1) DMSO solution of 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium is prepared；
(2) DMSO solution of acetic acid holmium is prepared；
(3) polyvinylpyrrolidone is added into the solution of step (1), be uniformly mixed, and be warming up to 200 DEG C, it is permanent
Warm 0.1h；
(4) DMSO solution of the acetic acid holmium of step (2) preparation is added, 0.1h is reacted, after reaction terminates, uses deionized water
Dialyse 10h, centrifugation, that is, described dual-mode contrast medium is made.
In the present embodiment, 2- phenylchinolines 3, the synthetic method of 3 '-bipyridyl dicarboxylic acids complex of iridium is as follows：
Weigh 2- phenylchinoline iridium dichloro bridge complexs (0.1-5g) and 2,2 '-bipyridyl -3,3 '-dicarboxylic acids (0.2-
10g) it is placed in 100mL three-neck flask, in N2Under protection, 5-60 minutes are vacuumized, fill N2About 10-60 minutes；Add 5-15mL
CH2Cl2With 5-15mL CH3OH, back flow reaction 6-24 hours obtain red solution；After reaction terminates, filter, use CH2Cl2With
CH3After OH washings, dry；Use CH2Cl2/CH3OH(10：1, v/v) silicagel column is crossed, you can 2- phenylchinolines 3,3 '-connection pyrrole is made
Diphosphoglyceric acid's complex of iridium.
In step (1), 2- phenylchinolines 3, the mass concentration of 3 '-bipyridyl dicarboxylic acids complex of iridium is 10mg/mL.
In step (2), the mass concentration of acetic acid holmium is 10mg/mL.
The mass ratio of 2- phenylchinolines 3,3 '-bipyridyl dicarboxylic acids complex of iridium and polyvinylpyrrolidone, acetic acid holmium is：
500：50：500.
Ultrasound made from the present embodiment/magnetic resonance dual-mode contrast medium be used for ultrasonic contrast imaging and magnetic resonance radiography into
Picture.
Embodiment 7：
The present embodiment ultrasound/magnetic resonance dual-mode contrast medium, the contrast agent are surface using polyvinyl pyrrolidon modified
Coordination polymer nanoparticle contrast agent, there is cavity structure, and institute inside the coordination polymer nanoparticle contrast agent
Also doped with rare earth element Ir and Ho in the coordination polymer nanoparticle contrast agent stated.
Wherein, the chemical structural formula of coordination polymer nanoparticle contrast agent is：
In the present embodiment, in coordination polymer nanoparticle contrast agent, rare earth element Ir weight/mass percentage composition is 2%,
Rare earth element Ho weight/mass percentage composition is 1%.The particle diameter of coordination polymer nanoparticle contrast agent is 100nm, and wall thickness is
20nm。
Preparation method specifically includes following steps：
(1) DMSO solution of 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium is prepared；
(2) DMSO solution of acetic acid holmium is prepared；
(3) polyvinylpyrrolidone is added into the solution of step (1), be uniformly mixed, and be warming up to 30 DEG C, constant temperature
2h；
(4) DMSO solution of the acetic acid holmium of step (2) preparation is added, 48h is reacted, after reaction terminates, uses deionized water
Dialyse 12h, centrifugation, that is, described dual-mode contrast medium is made.
In the present embodiment, 2- phenylchinolines 3, the synthetic method of 3 '-bipyridyl dicarboxylic acids complex of iridium is as follows：
Weigh 2- phenylchinoline iridium dichloro bridge complexs (0.1-5g) and 2,2 '-bipyridyl -3,3 '-dicarboxylic acids (0.2-
10g) it is placed in 100mL three-neck flask, in N2Under protection, 5-60 minutes are vacuumized, fill N2About 10-60 minutes；Add 5-15mL
CH2Cl2With 5-15mL CH3OH, back flow reaction 6-24 hours obtain red solution；After reaction terminates, filter, use CH2Cl2With
CH3After OH washings, dry；Use CH2Cl2/CH3OH(10：1, v/v) silicagel column is crossed, you can 2- phenylchinolines 3,3 '-connection pyrrole is made
Diphosphoglyceric acid's complex of iridium.
In step (1), 2- phenylchinolines 3, the mass concentration of 3 '-bipyridyl dicarboxylic acids complex of iridium is 0.01mg/mL.
In step (2), the mass concentration of acetic acid holmium is 0.01mg/mL.
The mass ratio of 2- phenylchinolines 3,3 '-bipyridyl dicarboxylic acids complex of iridium and polyvinylpyrrolidone, acetic acid holmium is
0.001：0.1：0.001.
Ultrasound made from the present embodiment/magnetic resonance dual-mode contrast medium be used for ultrasonic contrast imaging and magnetic resonance radiography into
Picture.
Embodiment 8：
The present embodiment ultrasound/magnetic resonance dual-mode contrast medium, the contrast agent are surface using polyvinyl pyrrolidon modified
Coordination polymer nanoparticle contrast agent, there is cavity structure, and institute inside the coordination polymer nanoparticle contrast agent
Also doped with rare earth element Ir and Ho in the coordination polymer nanoparticle contrast agent stated.
Wherein, the chemical structural formula of coordination polymer nanoparticle contrast agent is：
In the present embodiment, in coordination polymer nanoparticle contrast agent, rare earth element Ir weight/mass percentage composition is 25%,
Rare earth element Ho weight/mass percentage composition is 20%.The particle diameter of coordination polymer nanoparticle contrast agent is 400nm, and wall thickness is
60nm。
Preparation method specifically includes following steps：
(1) DMSO solution of 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium is prepared；
(2) DMSO solution of acetic acid holmium is prepared；
(3) polyvinylpyrrolidone is added into the solution of step (1), be uniformly mixed, and be warming up to 120 DEG C, it is permanent
Warm 1h；
(4) DMSO solution of the acetic acid holmium of step (2) preparation is added, 24h is reacted, after reaction terminates, uses deionized water
Dialyse 10h, centrifugation, that is, described dual-mode contrast medium is made.
In the present embodiment, 2- phenylchinolines 3, the synthetic method of 3 '-bipyridyl dicarboxylic acids complex of iridium is as follows：
Weigh 2- phenylchinoline iridium dichloro bridge complexs (0.1-5g) and 2,2 '-bipyridyl -3,3 '-dicarboxylic acids (0.2-
10g) it is placed in 100mL three-neck flask, in N2Under protection, 5-60 minutes are vacuumized, fill N2About 10-60 minutes；Add 5-15mL
CH2Cl2With 5-15mL CH3OH, back flow reaction 6-24 hours obtain red solution；After reaction terminates, filter, use CH2Cl2With
CH3After OH washings, dry；Use CH2Cl2/CH3OH(10：1, v/v) silicagel column is crossed, you can 2- phenylchinolines 3,3 '-connection pyrrole is made
Diphosphoglyceric acid's complex of iridium.
In step (1), 2- phenylchinolines 3, the mass concentration of 3 '-bipyridyl dicarboxylic acids complex of iridium is 2mg/mL.
In step (2), the mass concentration of acetic acid holmium is 2mg/mL.
The mass ratio of 2- phenylchinolines 3,3 '-bipyridyl dicarboxylic acids complex of iridium and polyvinylpyrrolidone, acetic acid holmium is
10：1：10.
Ultrasound made from the present embodiment/magnetic resonance dual-mode contrast medium be used for ultrasonic contrast imaging and magnetic resonance radiography into
Picture.
Embodiment 9：
The present embodiment ultrasound/magnetic resonance dual-mode contrast medium, the contrast agent are surface using polyvinyl pyrrolidon modified
Coordination polymer nanoparticle contrast agent, there is cavity structure, and institute inside the coordination polymer nanoparticle contrast agent
Also doped with rare earth element Ir and Ho in the coordination polymer nanoparticle contrast agent stated.
Wherein, the chemical structural formula of coordination polymer nanoparticle contrast agent is：
In the present embodiment, in coordination polymer nanoparticle contrast agent, rare earth element Ir weight/mass percentage composition is 30%,
Rare earth element Ho weight/mass percentage composition is 25%.The particle diameter of coordination polymer nanoparticle contrast agent is 500nm, and wall thickness is
80nm。
Preparation method specifically includes following steps：
(1) DMSO solution of 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium is prepared；
(2) DMSO solution of acetic acid holmium is prepared；
(3) polyvinylpyrrolidone is added into the solution of step (1), be uniformly mixed, and be warming up to 165 DEG C, it is permanent
Warm 0.5h；
(4) DMSO solution of the acetic acid holmium of step (2) preparation is added, 12h is reacted, after reaction terminates, uses deionized water
Dialyse 12h, centrifugation, that is, described dual-mode contrast medium is made.
In the present embodiment, 2- phenylchinolines 3, the synthetic method of 3 '-bipyridyl dicarboxylic acids complex of iridium is as follows：
Weigh 2- phenylchinoline iridium dichloro bridge complexs (0.1-5g) and 2,2 '-bipyridyl -3,3 '-dicarboxylic acids (0.2-
10g) it is placed in 100mL three-neck flask, in N2Under protection, 5-60 minutes are vacuumized, fill N2About 10-60 minutes；Add 5-15mL
CH2Cl2With 5-15mL CH3OH, back flow reaction 6-24 hours obtain red solution；After reaction terminates, filter, use CH2Cl2With
CH3After OH washings, dry；Use CH2Cl2/CH3OH(10：1, v/v) silicagel column is crossed, you can 2- phenylchinolines 3,3 '-connection pyrrole is made
Diphosphoglyceric acid's complex of iridium.
In step (1), 2- phenylchinolines 3, the mass concentration of 3 '-bipyridyl dicarboxylic acids complex of iridium is 8mg/mL.
In step (2), the mass concentration of acetic acid holmium is 8mg/mL.
The mass ratio of 2- phenylchinolines 3,3 '-bipyridyl dicarboxylic acids complex of iridium and polyvinylpyrrolidone, acetic acid holmium is
200：35：200.
Ultrasound made from the present embodiment/magnetic resonance dual-mode contrast medium be used for ultrasonic contrast imaging and magnetic resonance radiography into
Picture.
Claims (8)
1. a kind of ultrasound/magnetic resonance dual-mode contrast medium, it is characterised in that the contrast agent is that surface uses polyvinylpyrrolidone
The coordination polymer nanoparticle contrast agent of modification, coordination polymer nanoparticle contrast agent inside have cavity structure, and
And also doped with rare earth element Ir and Ho in described coordination polymer nanoparticle contrast agent.
A kind of 2. ultrasound/magnetic resonance dual-mode contrast medium according to claim 1, it is characterised in that described polycomplexation
The chemical structural formula of compound nanoparticle contrast agent is：
A kind of 3. ultrasound/magnetic resonance dual-mode contrast medium according to claim 1, it is characterised in that described polycomplexation
In compound nanoparticle contrast agent, rare earth element Ir weight/mass percentage composition is 2-40%, and rare earth element Ho quality percentage contains
Measure as 1-30%.
A kind of 4. ultrasound/magnetic resonance dual-mode contrast medium according to claim 1, it is characterised in that described polycomplexation
The external diameter of compound nanoparticle contrast agent is 100-800nm, wall thickness 20-100nm.
A kind of 5. preparation method of ultrasound/magnetic resonance dual-mode contrast medium as claimed in claim 1, it is characterised in that the party
Method specifically includes following steps：
(1) DMSO solution of 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium is prepared；
(2) DMSO solution of acetic acid holmium is prepared；
(3) polyvinylpyrrolidone is added into the solution of step (1), be uniformly mixed, and be warming up to 30-200 DEG C, constant temperature
0.1-2h；
(4) DMSO solution of the acetic acid holmium of step (2) preparation is added, 0.1-48h is reacted, after reaction terminates, uses deionized water
Dialyse 10-12h, centrifugation, that is, described dual-mode contrast medium is made.
A kind of 6. preparation method of ultrasound/magnetic resonance dual-mode contrast medium according to claim 5, it is characterised in that step
Suddenly the mass concentration of 2- phenylchinoline 3,3 '-bipyridyl dicarboxylic acids complex of iridium described in (1) is 0.01-10mg/mL.
A kind of 7. preparation method of ultrasound/magnetic resonance dual-mode contrast medium according to claim 5, it is characterised in that step
Suddenly the mass concentration of the acetic acid holmium described in (2) is 0.01-10mg/mL.
A kind of 8. preparation method of ultrasound/magnetic resonance dual-mode contrast medium according to claim 5, it is characterised in that institute
The mass ratio of 2- the phenylchinolines 3,3 '-bipyridyl dicarboxylic acids complex of iridium and polyvinylpyrrolidone, acetic acid holmium stated is：
0.001-500：0.1-50：0.001-500.
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