技术领域technical field
本发明属于医学成像技术领域，涉及一种超声/磁共振双模式造影剂及其制备方法与应用。The invention belongs to the technical field of medical imaging, and relates to an ultrasound/magnetic resonance dual-mode contrast agent and a preparation method and application thereof.
背景技术Background technique
分子影像学是医学影像技术和分子生物学结合的学科，该学科利用成像仪器可以得到机体早期的病变信息。在众多的影像学中，超声成像医疗成本低，可获得机体组织任意断层的成像图像，具有成像快、器官运动可见、诊断及时等特点，无痛苦，具有非危险性、非损伤性；而核磁共振成像，则由于其可进行多参数成像，提供诊断信息丰富，快速安全，病灶与正常部位对照明显，因而现已得到广泛应用。Molecular imaging is a subject that combines medical imaging technology and molecular biology. In this subject, early disease information of the body can be obtained by using imaging instruments. Among the many imaging studies, ultrasound imaging has low medical cost, can obtain imaging images of any section of body tissue, has the characteristics of fast imaging, visible organ movement, timely diagnosis, etc., is painless, non-dangerous, and non-invasive; Resonance imaging, because it can perform multi-parameter imaging, provides rich diagnostic information, is fast and safe, and has a clear contrast between lesions and normal parts, has been widely used.
超声成像是利用超声波物理特性和人体器官在声学上的差异，以波形、曲线和图像的形式来体现机体的差异，因而在进行疾病的诊断检查，超声成像现已在医学上得到广泛应用。磁共振成像主要利用生物体不同组织中水分子质子在外加磁场影像下产生不同的共振信号(信号强弱取决于组织内水的含量和水质子的弛豫时间)来成像。但对于病灶部位病灶造影不够明显，简单的超声或核磁成像无法达到病变组织的确认，造成误诊的可能性提高。Ultrasound imaging uses the physical characteristics of ultrasound and the acoustic differences of human organs to reflect the differences in the body in the form of waveforms, curves and images. Therefore, ultrasonic imaging has been widely used in medicine for the diagnosis and examination of diseases. Magnetic resonance imaging mainly uses the different resonance signals generated by water molecule protons in different tissues of the organism under the image of an external magnetic field (the strength of the signal depends on the water content in the tissue and the relaxation time of water protons) for imaging. However, the angiography of the lesion is not obvious enough, and simple ultrasound or MRI cannot confirm the lesion tissue, which increases the possibility of misdiagnosis.
在超声成像及磁共振成像应用方面，造影剂的存在能够较好的弥补病灶组织造影分辨率低的问题。例如，超声造影剂一般是具有空腔结构的材料，而且为了便于后期体内循环，材料尺寸不宜过大，为了有更好的超声效果，其他条件一致的情况下(如正常体内循环、散射性、衰减速度以及循环过程不破裂等)，材料尺寸固定时，空腔越大，对成像效果越有利；核磁成像造影剂的存在也能更有效的增大病灶与正常组织对比度，从而有利于更早期、更深层的病灶的发现。In the application of ultrasound imaging and magnetic resonance imaging, the presence of contrast agents can better compensate for the low resolution of lesion tissue imaging. For example, ultrasound contrast agents are generally materials with a cavity structure, and in order to facilitate later internal circulation, the size of the material should not be too large. In order to have a better ultrasound effect, under the same conditions (such as normal internal circulation, scattering, Attenuation speed and cycle process do not rupture, etc.), when the size of the material is fixed, the larger the cavity, the more favorable the imaging effect; the presence of MRI contrast agents can also more effectively increase the contrast between the lesion and normal tissue, which is conducive to earlier stage imaging. , the discovery of deeper lesions.
然而，目前在造影剂的研究方面，现有的临床所使用的造影剂只能用于一种影像学手段来检查，而对于既能用于超声造影又能用于磁共振造影的造影剂的研究甚少，这无疑会限制多模式造影技术的发展。因此，研究开发一种双模式造影剂，即能用于超声造影和磁共振造影，则显得尤为重要。However, currently in the research of contrast agents, the existing clinically used contrast agents can only be used for one imaging method for inspection, and the contrast agents that can be used for both ultrasound and magnetic resonance imaging There are few studies, which will undoubtedly limit the development of multimodal imaging technology. Therefore, it is particularly important to research and develop a dual-mode contrast agent that can be used for contrast-enhanced ultrasound and magnetic resonance imaging.
申请号为201410600719.9的中国发明专利公布了一种超声/磁共振双模态造影剂、其制备方法及应用，所述的双模态造影剂以核磁共振显影的纳米粒子混悬液为原料，经喷雾干燥工艺制成空心球形纳米粒子聚集体，构建超声/磁共振显影功能集于一身的双模态造影剂，其中，核磁共振显影的纳米粒子为超顺磁氧化铁纳米粒子、超顺磁氧化锰纳米粒子、铁酸钴磁性纳米粒子、铁酸锰磁性纳米粒子中的一种或几种的组合物，并且核磁共振显影的纳米粒子为核壳结构；所述核为超顺磁氧化铁纳米粒子、超顺磁氧化锰纳米粒子、铁酸钴磁性纳米粒子、铁酸锰磁性纳米粒子中的一种，壳为二氧化硅。The Chinese invention patent with application number 201410600719.9 discloses an ultrasound/magnetic resonance dual-mode contrast agent, its preparation method and application. Hollow spherical nanoparticle aggregates are made by spray drying process to construct a dual-mode contrast agent with integrated ultrasound/magnetic resonance imaging functions. Among them, the nanoparticles for nuclear magnetic resonance imaging are superparamagnetic iron oxide nanoparticles, superparamagnetic oxide A composition of one or more of manganese nanoparticles, cobalt ferrite magnetic nanoparticles, and manganese ferrite magnetic nanoparticles, and the nanoparticles developed by nuclear magnetic resonance have a core-shell structure; the core is a superparamagnetic iron oxide nanometer Particles, superparamagnetic manganese oxide nanoparticles, cobalt ferrite magnetic nanoparticles, manganese ferrite magnetic nanoparticles, the shell is silicon dioxide.
本发明相比于上述对比专利文献具有下列优点：Compared with the above-mentioned comparative patent documents, the present invention has the following advantages:
1)对比专利文献的技术方案中，首先合成核磁共振显影的纳米粒子，再进行喷雾处理，进而得到中空材料，而与对比专利文献相比，本发明技术方案简单，采用一步法即可获得空心纳米材料；1) In the technical solution of the comparative patent document, the nanoparticles developed by nuclear magnetic resonance are first synthesized, and then sprayed to obtain a hollow material. Compared with the comparative patent document, the technical solution of the present invention is simple, and the hollow material can be obtained by a one-step method. nanomaterials;
2)对比专利文献对核磁共振显影的纳米粒子喷雾后进行处理时，参数对产品影响很大，会直接决定产品的结构形态，如果参数选择不合适，则无法制备出中空球形纳米粒子聚集体，不能作为超声/磁共振双模态造影剂，而本发明获得的空心纳米材料结构稳定，后处理不会对产品的形态产生影响；2) Compared with the patent literature, when processing the nanoparticles of NMR imaging after spraying, the parameters have a great influence on the product, which will directly determine the structural shape of the product. If the parameters are not selected properly, hollow spherical nanoparticle aggregates cannot be prepared. It cannot be used as an ultrasound/magnetic resonance dual-mode contrast agent, but the hollow nanomaterial obtained by the present invention has a stable structure, and post-processing will not affect the shape of the product;
3)本发明技术方案的合成步骤更为简单，合成得到的纳米材料，性能稳定，不受后处理参数的影响，用于超声/磁共振双模态成像时，持续时间长，可以重复成像。3) The synthesis steps of the technical solution of the present invention are simpler, and the synthesized nanomaterials have stable performance and are not affected by post-processing parameters. When used for ultrasound/magnetic resonance dual-modal imaging, the duration is long and repeated imaging can be performed.
发明内容Contents of the invention
本发明的目的就是为了克服上述现有技术存在的缺陷而提供一种具有优异的水溶性及生物相容性，兼具超声成像与核磁共振成像功能的超声/磁共振双模式造影剂及其制备方法与应用，借助于现有的医学手段，方便快捷地确诊病灶，降低误诊率，为病变的治疗提供保障。The purpose of the present invention is to provide an ultrasound/magnetic resonance dual-mode contrast agent with excellent water solubility and biocompatibility and functions of ultrasound imaging and nuclear magnetic resonance imaging in order to overcome the above-mentioned defects in the prior art and its preparation The method and application, with the help of existing medical means, can conveniently and quickly diagnose the lesion, reduce the misdiagnosis rate, and provide guarantee for the treatment of the lesion.
本发明的目的可以通过以下技术方案来实现：The purpose of the present invention can be achieved through the following technical solutions:
一种超声/磁共振双模式造影剂，该造影剂为表面采用聚乙烯吡咯烷酮修饰的配位聚合物纳米粒子造影剂，该配位聚合物纳米粒子造影剂内部具有空腔结构，并且所述的配位聚合物纳米粒子造影剂中还掺杂有稀土元素Ir及Ho。An ultrasound/magnetic resonance dual-mode contrast agent, the contrast agent is a coordination polymer nanoparticle contrast agent whose surface is modified with polyvinylpyrrolidone, the coordination polymer nanoparticle contrast agent has a cavity structure inside, and the The coordination polymer nanoparticle contrast agent is also doped with rare earth elements Ir and Ho.
所述的配位聚合物纳米粒子造影剂的化学结构式为：The chemical structural formula of the coordination polymer nanoparticle contrast agent is:
所述的配位聚合物纳米粒子造影剂中，稀土元素Ir的质量百分含量为2-40％，稀土元素Ho的质量百分含量为1-30％。In the coordination polymer nanoparticle contrast agent, the mass percent content of the rare earth element Ir is 2-40%, and the mass percentage content of the rare earth element Ho is 1-30%.
所述的配位聚合物纳米粒子造影剂的粒径(指外径)为100-800nm，壁厚为20-100nm。The particle size (outer diameter) of the coordination polymer nanoparticle contrast agent is 100-800nm, and the wall thickness is 20-100nm.
一种超声/磁共振双模式造影剂的制备方法，该方法具体包括以下步骤：A method for preparing an ultrasound/magnetic resonance dual-mode contrast agent, the method specifically comprising the following steps:
(1)配制2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液；(1) prepare the DMSO solution of 2-phenylquinoline 3,3'-bipyridyl iridium dicarboxylate complex;
(2)配制醋酸钬的DMSO溶液；(2) prepare the DMSO solution of holmium acetate;
(3)向步骤(1)的溶液中加入聚乙烯吡咯烷酮，搅拌混合均匀，并升温至30-200℃，恒温0.1-2h；(3) Add polyvinylpyrrolidone to the solution in step (1), stir and mix evenly, and raise the temperature to 30-200°C, and keep the temperature constant for 0.1-2h;
(4)再加入步骤(2)配制的醋酸钬的DMSO溶液，反应0.1-48h，反应结束后，用去离子水透析10-12h，离心，即制得所述的双模式造影剂。(4) Add the DMSO solution of holmium acetate prepared in step (2) and react for 0.1-48 hours. After the reaction, dialyze with deionized water for 10-12 hours and centrifuge to prepare the dual-mode contrast agent.
步骤(1)中所述的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的质量浓度为0.01-10mg/mL。The mass concentration of the iridium complex of 2-phenylquinoline 3,3'-bipyridinedicarboxylate described in step (1) is 0.01-10 mg/mL.
步骤(2)中所述的醋酸钬的质量浓度为0.01-10mg/mL。The mass concentration of holmium acetate described in step (2) is 0.01-10mg/mL.
所述的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物与聚乙烯吡咯烷酮、醋酸钬的质量比为：0.001-500：0.1-50：0.001-500。The mass ratio of the iridium complex of 2-phenylquinoline 3,3'-bipyridinedicarboxylate to polyvinylpyrrolidone and holmium acetate is: 0.001-500:0.1-50:0.001-500.
一种超声/磁共振双模式造影剂的应用，所述的双模式造影剂用于超声造影成像及磁共振造影成像。An application of an ultrasound/magnetic resonance dual-mode contrast agent, and the dual-mode contrast agent is used for ultrasound contrast imaging and magnetic resonance contrast imaging.
本发明中，所述的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的合成方法如下：In the present invention, the synthetic method of described 2-phenylquinoline 3,3'-bipyridyl iridium dicarboxylate complex is as follows:
称取2-苯基喹啉铱二氯桥配合物(0.1-5g)和2,2’-联吡啶-3,3’-二羧酸(0.2-10g)置于100mL的三颈烧瓶中，在N2保护下，抽真空5-60分钟，充N2约10-60分钟；加入5-15mL的CH2Cl2和5-15mL的CH3OH，回流反应6-24小时得到红色溶液；反应结束后，抽滤，用CH2Cl2和CH3OH洗涤后，干燥；用CH2Cl2/CH3OH(10：1，v/v)过硅胶柱，即可制得所述的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物。Weigh 2-phenylquinoline-iridium dichloro bridge complex (0.1-5g) and 2,2'-bipyridine-3,3'-dicarboxylic acid (0.2-10g) into a 100mL three-necked flask, Under the protection ofN2 , vacuumize for 5-60 minutes, fill withN2 for about 10-60 minutes; add 5-15mL ofCH2Cl2 and5-15mLof CH3OH, and reflux for 6-24 hours to obtain a red solution; After the reaction, filter with suction, wash with CH2 Cl2 and CH3 OH, and dry; use CH2 Cl2 /CH3 OH (10:1, v/v) to pass through a silica gel column to obtain the 2-Phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex.
本发明中，2-苯基喹啉3,3’-联吡啶二羧酸铱配合物、聚乙烯吡咯烷酮及醋酸钬这三种物质之间，是通过配位自组装一步法合成制得水溶性的配位聚合物纳米粒子，化学反应式如下：In the present invention, among the three substances of 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex, polyvinylpyrrolidone and holmium acetate, a water-soluble The coordination polymer nanoparticles, the chemical reaction formula is as follows:
聚乙烯吡咯烷酮(简称：PVP)是一种水溶性高分子化合物，具有水溶性高分子化合物的一般性质：胶体保护作用、成膜性、粘结性、吸湿性、增溶或凝聚作用，但其最具特色并受到人们高度重视的性质是其优异的溶解性能及生理相容性。在合成高分子中像PVP这样既溶于水，又溶于大部分有机溶剂、毒性很低、生理相溶性好的并不多见，特别是在医药、食品、化妆品这些与人们健康密切相关的领域中，随着其原料丁内酯价格的降低，必将展示其发展的良好前景。从生物学的观点来看，PVP的分子结构特色类似于用简单的蛋白质模型的那种结构，甚至于它的水溶性对某些小分子的配合能力以及能够被某些蛋白质的沉淀剂硫酸铵、三氯乙酸、单宁酸和酚类所沉淀等特性也和蛋白质相溶，以致于使PVP被广泛地用作药物制剂的辅料。Polyvinylpyrrolidone (abbreviation: PVP) is a water-soluble polymer compound, which has the general properties of water-soluble polymer compounds: colloidal protection, film-forming, cohesiveness, hygroscopicity, solubilization or coagulation, but its The most distinctive and highly valued properties are its excellent solubility and physiological compatibility. Among synthetic polymers, PVP is soluble in both water and most organic solvents, with low toxicity and good physiological compatibility, especially in medicine, food, cosmetics, which are closely related to people's health. In the field, with the price reduction of its raw material butyrolactone, it will show a good prospect for its development. From a biological point of view, the molecular structure of PVP is similar to that of a simple protein model, even its water solubility is compatible with some small molecules and it can be precipitated by certain proteins such as ammonium sulfate, The properties of trichloroacetic acid, tannic acid and phenolic precipitation are also compatible with proteins, so that PVP is widely used as an auxiliary material for pharmaceutical preparations.
本发明双模式造影剂内部的空腔结构的大小，可通过改变反应时间来进行调节，随着时间的延长，纳米材料的空腔体积会逐渐变大。本发明制得的双模式造影剂内部空腔结构的体积一般占纳米粒子总体积的20-80％。The size of the cavity structure inside the dual-mode contrast agent of the present invention can be adjusted by changing the reaction time. As time goes on, the volume of the cavity of the nanometer material will gradually increase. The volume of the internal cavity structure of the dual-mode contrast agent prepared by the present invention generally accounts for 20-80% of the total volume of the nanoparticles.
本发明制得的双模式造影剂用于核磁共振造影成像时，相关的磁场下的成像参数条件如下：TR/TE值为1500/15.6毫秒，矩阵为256×320，谱带宽度为300.3Hz/Px，层厚度为1毫米。用于超声造影成像时，相关的成像参数条件如下：样品是在超声诊疗仪器(MyLabTwice；Esaote SpA,Genova,Italy)B模式下所测而得，其中心频率为13MHz和22MHz。When the dual-mode contrast agent prepared by the present invention is used for nuclear magnetic resonance imaging, the imaging parameter conditions under the relevant magnetic field are as follows: the TR/TE value is 1500/15.6 milliseconds, the matrix is 256×320, and the spectral band width is 300.3 Hz/ Px, with a layer thickness of 1 mm. When used for contrast-enhanced ultrasound imaging, the relevant imaging parameters are as follows: the sample is measured in B mode of an ultrasonic diagnostic and therapeutic instrument (MyLabTwice; Esaote SpA, Genova, Italy), and its center frequency is 13MHz and 22MHz.
与现有技术相比，本发明应用简单的方法合成了一种配合物纳米粒子，该纳米粒子具有较为突出的空心结构，其形貌均一，分散性好，稳定性优良，由于该配合物纳米粒子中包含有金属Ho，这使其具有一定的弛豫率，在核磁造影仪下表现出良好的T2成像效果；另外，在材料结构上，由于其具有较为突出的空心结构，超声成像效果也非常明显。本发明造影剂同时具备了核磁共振成像和超声成像的功能，可作为一种潜在的核磁、超声双造影剂，合成工艺简单，原料易得，对环境无污染，具有很好的应用前景。Compared with the prior art, the present invention uses a simple method to synthesize a complex nanoparticle, which has a relatively prominent hollow structure, uniform appearance, good dispersion, and excellent stability. The particles contain metal Ho, which makes it have a certain relaxation rate, and shows a good T2 imaging effect under the MRI apparatus; in addition, in terms of material structure, due to its prominent hollow structure, the ultrasonic imaging effect Also very obvious. The contrast agent of the invention has the functions of nuclear magnetic resonance imaging and ultrasonic imaging at the same time, and can be used as a potential double contrast agent of nuclear magnetic resonance and ultrasound. The synthesis process is simple, the raw materials are easy to obtain, and the environment is not polluted, so it has a good application prospect.
附图说明Description of drawings
图1为实施例1制备所得双模式造影剂的扫描电镜图谱；Fig. 1 is the scanning electron microscope atlas of the dual-mode contrast agent prepared in Example 1;
图2为实施例1制备所得双模式造影剂的透射电镜图谱；Figure 2 is the transmission electron microscope spectrum of the dual-mode contrast agent prepared in Example 1;
图3为实施例1制备所得双模式造影剂在不同浓度下的超声造影成像图(其中，a、b、c、d、e分别对应的浓度为0μg/mL、100μg/mL、200μg/mL、400μg/mL、600μg/mL)；Fig. 3 is the contrast-enhanced ultrasound image of the dual-mode contrast agent prepared in Example 1 at different concentrations (where a, b, c, d, and e respectively correspond to concentrations of 0 μg/mL, 100 μg/mL, 200 μg/mL, 400μg/mL, 600μg/mL);
图4为实施例1制备所得双模式造影剂在不同浓度下的核磁共振造影成像图。FIG. 4 is an MRI image of the dual-mode contrast agent prepared in Example 1 at different concentrations.
具体实施方式Detailed ways
下面结合附图和具体实施例对本发明进行详细说明。The present invention will be described in detail below in conjunction with the accompanying drawings and specific embodiments.
实施例1：Example 1:
配制0.3mg/mL的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液和0.3mg/mL的醋酸钬的DMSO溶液，待用。取2mL配置好的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液置于单口烧瓶中，并加入10mg聚乙烯吡咯烷酮(PVP K30)，混合均匀后，将其升温到50℃，恒温0.1h，再取2mL上述醋酸钬溶液到烧瓶中，反应0.25h。反应结束后，用去离子水透析12h，再离心洗涤3次，将得到的样品分散于去离子水中，进行超声和核磁共振测试。Prepare 0.3 mg/mL DMSO solution of 2-phenylquinoline 3,3'-bipyridine dicarboxylate iridium complex and 0.3 mg/mL holmium acetate solution in DMSO for use. Take 2mL of the DMSO solution of the prepared 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex and place it in a single-necked flask, and add 10mg of polyvinylpyrrolidone (PVP K30), mix well, and put it Raise the temperature to 50°C, keep the temperature constant for 0.1h, then take 2mL of the above-mentioned holmium acetate solution into the flask, and react for 0.25h. After the reaction, dialyze with deionized water for 12 hours, centrifuge and wash 3 times, disperse the obtained sample in deionized water, and perform ultrasonic and nuclear magnetic resonance tests.
图1为本实施例制得的双模式造影剂的扫描电镜图谱，由图中可以看出，所述的造影剂为球形颗粒，且分散性好，无团聚现象。FIG. 1 is a scanning electron microscope spectrum of the dual-mode contrast agent prepared in this example. It can be seen from the figure that the contrast agent is spherical particles with good dispersibility and no agglomeration.
图2为本实施例制得的双模式造影剂的透射电镜图谱，由图中可以看出，所述的配位聚合物纳米粒子造影剂的粒径为100-800nm，壁厚为20-100nm。Fig. 2 is the TEM spectrum of the dual-mode contrast agent prepared in this embodiment, as can be seen from the figure, the particle size of the coordination polymer nanoparticle contrast agent is 100-800nm, and the wall thickness is 20-100nm .
图3为本实施例制得的双模式造影剂的透射电镜图谱，由图中可以看出，所述的配位聚合物纳米粒子造影剂由于其具有较为突出的空心结构，超声成像效果也非常明显。Figure 3 is the transmission electron microscope spectrum of the dual-mode contrast agent prepared in this example. It can be seen from the figure that the ultrasound imaging effect of the coordination polymer nanoparticle contrast agent is also very good due to its prominent hollow structure. obvious.
图4为本实施例制得的双模式造影剂的透射电镜图谱，由图中可以看出，所述的配位聚合物纳米粒子造影剂，由于该配合物纳米粒子中包含有金属Ho，这使其具有一定的弛豫率，在核磁造影仪下表现出良好的T2成像效果。Fig. 4 is the transmission electron microscopy spectrum of the dual-mode contrast agent prepared in this embodiment. It can be seen from the figure that the coordination polymer nanoparticle contrast agent contains metal Ho in the complex nanoparticle. It has a certain relaxation rate, and shows a goodT2 imaging effect under the MRI apparatus.
实施例2：Example 2:
配制0.5mg/mL的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液和0.7mg/mL的醋酸钬的DMSO溶液，待用。取2mL配置好的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液置于单口烧瓶中，并加入20mg聚乙烯吡咯烷酮(PVP K30)，混合均匀后，将其升温到70℃，恒温0.2h，再取2mL上述醋酸钬溶液到烧瓶中，反应0.5h。反应结束后，用去离子水透析12h，再离心洗涤3次，将得到的样品分散于去离子水中，进行超声和核磁共振测试。Prepare 0.5 mg/mL DMSO solution of 2-phenylquinoline 3,3'-bipyridyl dicarboxylate iridium complex and 0.7 mg/mL holmium acetate solution in DMSO for use. Take 2mL of the DMSO solution of the prepared 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex and place it in a single-necked flask, and add 20mg of polyvinylpyrrolidone (PVP K30), mix well, and put it Raise the temperature to 70°C, keep the temperature constant for 0.2h, then take 2mL of the above-mentioned holmium acetate solution into the flask, and react for 0.5h. After the reaction, dialyze with deionized water for 12 hours, centrifuge and wash 3 times, disperse the obtained sample in deionized water, and perform ultrasonic and nuclear magnetic resonance tests.
实施例3：Example 3:
配制0.5mg/mL的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液和0.9mg/mL的醋酸钬的DMSO溶液，待用。取5mL配置好的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液置于单口烧瓶中，并加入30mg聚乙烯吡咯烷酮(PVP K30)，混合均匀后，将其升温到70℃，恒温0.3h，再取2mL上述醋酸钬溶液到烧瓶中，反应1h。反应结束后，用去离子水透析12h，再离心洗涤3次，将得到的样品分散于去离子水中，进行超声和核磁共振测试。Prepare 0.5 mg/mL DMSO solution of 2-phenylquinoline 3,3'-bipyridyl iridium complex and 0.9 mg/mL holmium acetate solution in DMSO for use. Take 5mL of the DMSO solution of the prepared 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex and place it in a single-necked flask, and add 30mg of polyvinylpyrrolidone (PVP K30), mix well, and put it Raise the temperature to 70°C, keep the temperature constant for 0.3h, then take 2mL of the above-mentioned holmium acetate solution into the flask, and react for 1h. After the reaction, dialyze with deionized water for 12 hours, centrifuge and wash 3 times, disperse the obtained sample in deionized water, and perform ultrasonic and nuclear magnetic resonance tests.
实施例4：Example 4:
配制0.7mg/mL的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液和0.9mg/mL的醋酸钬的DMSO溶液，待用。取5mL配置好的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液置于单口烧瓶中，并加入30mg聚乙烯吡咯烷酮(PVP K30)，混合均匀后，将其升温到90℃，恒温0.3h，再取2mL上述醋酸钬溶液到烧瓶中，反应2h。反应结束后，用去离子水透析12h，再离心洗涤3次，将得到的样品分散于去离子水中，进行超声和核磁共振测试。Prepare a DMSO solution of 0.7 mg/mL 2-phenylquinoline 3,3'-bipyridyl iridium complex and a 0.9 mg/mL holmium acetate solution in DMSO for use. Take 5mL of the DMSO solution of the prepared 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex and place it in a single-necked flask, and add 30mg of polyvinylpyrrolidone (PVP K30), mix well, and put it Raise the temperature to 90°C, keep the temperature constant for 0.3h, then take 2mL of the above-mentioned holmium acetate solution into the flask, and react for 2h. After the reaction, dialyze with deionized water for 12 hours, centrifuge and wash 3 times, disperse the obtained sample in deionized water, and perform ultrasonic and nuclear magnetic resonance tests.
实施例5：Example 5:
配制5mg/mL的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液和5mg/mL的醋酸钬的DMSO溶液，待用。取10mL配置好的2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液置于单口烧瓶中，并加入40mg聚乙烯吡咯烷酮(PVP K30)，混合均匀后，将其升温到90℃，恒温1h，再取10mL上述醋酸钬溶液到烧瓶中，反应10h。反应结束后，用去离子水透析12h，再离心洗涤3次，将得到的样品分散于去离子水中，进行超声和核磁共振测试。Prepare 5 mg/mL DMSO solution of 2-phenylquinoline 3,3'-bipyridyl dicarboxylate iridium complex and 5 mg/mL holmium acetate solution in DMSO for use. Take 10mL of the DMSO solution of the prepared 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex and place it in a single-necked flask, and add 40mg of polyvinylpyrrolidone (PVP K30), mix well, and put it Raise the temperature to 90°C, keep the temperature for 1h, then take 10mL of the above-mentioned holmium acetate solution into the flask, and react for 10h. After the reaction, dialyze with deionized water for 12 hours, centrifuge and wash 3 times, disperse the obtained sample in deionized water, and perform ultrasonic and nuclear magnetic resonance tests.
实施例6：Embodiment 6:
本实施例超声/磁共振双模式造影剂，该造影剂为表面采用聚乙烯吡咯烷酮修饰的配位聚合物纳米粒子造影剂，该配位聚合物纳米粒子造影剂内部具有空腔结构，并且所述的配位聚合物纳米粒子造影剂中还掺杂有稀土元素Ir及Ho。In this embodiment, the ultrasound/magnetic resonance dual-mode contrast agent is a coordination polymer nanoparticle contrast agent whose surface is modified with polyvinylpyrrolidone. The coordination polymer nanoparticle contrast agent has a cavity structure inside, and the The coordination polymer nanoparticle contrast agent is also doped with rare earth elements Ir and Ho.
其中，配位聚合物纳米粒子造影剂的化学结构式为：Wherein, the chemical structural formula of the coordination polymer nanoparticle contrast agent is:
本实施例中，配位聚合物纳米粒子造影剂中，稀土元素Ir的质量百分含量为40％，稀土元素Ho的质量百分含量为30％。配位聚合物纳米粒子造影剂的粒径为800nm，壁厚为100nm。In this embodiment, in the coordination polymer nanoparticle contrast agent, the mass percentage content of the rare earth element Ir is 40%, and the mass percentage content of the rare earth element Ho is 30%. The particle diameter of the coordination polymer nanoparticle contrast agent is 800nm, and the wall thickness is 100nm.
制备方法具体包括以下步骤：The preparation method specifically comprises the following steps:
(1)配制2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液；(1) prepare the DMSO solution of 2-phenylquinoline 3,3'-bipyridyl iridium dicarboxylate complex;
(2)配制醋酸钬的DMSO溶液；(2) prepare the DMSO solution of holmium acetate;
(3)向步骤(1)的溶液中加入聚乙烯吡咯烷酮，搅拌混合均匀，并升温至200℃，恒温0.1h；(3) Add polyvinylpyrrolidone to the solution in step (1), stir and mix evenly, and raise the temperature to 200°C, and keep the temperature constant for 0.1h;
(4)再加入步骤(2)配制的醋酸钬的DMSO溶液，反应0.1h，反应结束后，用去离子水透析10h，离心，即制得所述的双模式造影剂。(4) Add the DMSO solution of holmium acetate prepared in step (2) and react for 0.1 h. After the reaction, dialyze with deionized water for 10 h and centrifuge to obtain the dual-mode contrast agent.
本实施例中，2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的合成方法如下：In this example, the synthesis method of the iridium complex of 2-phenylquinoline 3,3'-bipyridinedicarboxylate is as follows:
称取2-苯基喹啉铱二氯桥配合物(0.1-5g)和2,2’-联吡啶-3,3’-二羧酸(0.2-10g)置于100mL的三颈烧瓶中，在N2保护下，抽真空5-60分钟，充N2约10-60分钟；加入5-15mL的CH2Cl2和5-15mL的CH3OH，回流反应6-24小时得到红色溶液；反应结束后，抽滤，用CH2Cl2和CH3OH洗涤后，干燥；用CH2Cl2/CH3OH(10：1，v/v)过硅胶柱，即可制得2-苯基喹啉3,3’-联吡啶二羧酸铱配合物。Weigh 2-phenylquinoline-iridium dichloro bridge complex (0.1-5g) and 2,2'-bipyridine-3,3'-dicarboxylic acid (0.2-10g) into a 100mL three-necked flask, Under the protection ofN2 , vacuumize for 5-60 minutes, fill withN2 for about 10-60 minutes; add 5-15mL ofCH2Cl2 and5-15mLof CH3OH, and reflux for 6-24 hours to obtain a red solution; After the reaction, filter with suction, wash with CH2 Cl2 and CH3 OH, and dry; use CH2 Cl2 /CH3 OH (10:1, v/v) to pass through a silica gel column to obtain 2-benzene Quinoline 3,3'-bipyridyl dicarboxylate iridium complexes.
步骤(1)中，2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的质量浓度为10mg/mL。In step (1), the mass concentration of the iridium complex of 2-phenylquinoline 3,3'-bipyridinedicarboxylate is 10 mg/mL.
步骤(2)中，醋酸钬的质量浓度为10mg/mL。In step (2), the mass concentration of holmium acetate is 10mg/mL.
2-苯基喹啉3,3’-联吡啶二羧酸铱配合物与聚乙烯吡咯烷酮、醋酸钬的质量比为：500：50：500。The mass ratio of 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex to polyvinylpyrrolidone and holmium acetate is 500:50:500.
本实施例制得的超声/磁共振双模式造影剂用于超声造影成像及磁共振造影成像。The ultrasound/magnetic resonance dual-mode contrast agent prepared in this example is used for ultrasound contrast imaging and magnetic resonance contrast imaging.
实施例7：Embodiment 7:
本实施例超声/磁共振双模式造影剂，该造影剂为表面采用聚乙烯吡咯烷酮修饰的配位聚合物纳米粒子造影剂，该配位聚合物纳米粒子造影剂内部具有空腔结构，并且所述的配位聚合物纳米粒子造影剂中还掺杂有稀土元素Ir及Ho。In this embodiment, the ultrasound/magnetic resonance dual-mode contrast agent is a coordination polymer nanoparticle contrast agent whose surface is modified with polyvinylpyrrolidone. The coordination polymer nanoparticle contrast agent has a cavity structure inside, and the The coordination polymer nanoparticle contrast agent is also doped with rare earth elements Ir and Ho.
其中，配位聚合物纳米粒子造影剂的化学结构式为：Wherein, the chemical structural formula of the coordination polymer nanoparticle contrast agent is:
本实施例中，配位聚合物纳米粒子造影剂中，稀土元素Ir的质量百分含量为2％，稀土元素Ho的质量百分含量为1％。配位聚合物纳米粒子造影剂的粒径为100nm，壁厚为20nm。In this embodiment, in the coordination polymer nanoparticle contrast agent, the mass percentage of the rare earth element Ir is 2%, and the mass percentage of the rare earth element Ho is 1%. The particle diameter of the coordination polymer nanoparticle contrast agent is 100nm, and the wall thickness is 20nm.
制备方法具体包括以下步骤：The preparation method specifically comprises the following steps:
(1)配制2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液；(1) prepare the DMSO solution of 2-phenylquinoline 3,3'-bipyridyl iridium dicarboxylate complex;
(2)配制醋酸钬的DMSO溶液；(2) prepare the DMSO solution of holmium acetate;
(3)向步骤(1)的溶液中加入聚乙烯吡咯烷酮，搅拌混合均匀，并升温至30℃，恒温2h；(3) Add polyvinylpyrrolidone to the solution in step (1), stir and mix evenly, and raise the temperature to 30° C., and keep the temperature for 2 hours;
(4)再加入步骤(2)配制的醋酸钬的DMSO溶液，反应48h，反应结束后，用去离子水透析12h，离心，即制得所述的双模式造影剂。(4) Add the DMSO solution of holmium acetate prepared in step (2) and react for 48 hours. After the reaction, dialyze with deionized water for 12 hours and centrifuge to obtain the dual-mode contrast agent.
本实施例中，2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的合成方法如下：In this example, the synthesis method of the iridium complex of 2-phenylquinoline 3,3'-bipyridinedicarboxylate is as follows:
称取2-苯基喹啉铱二氯桥配合物(0.1-5g)和2,2’-联吡啶-3,3’-二羧酸(0.2-10g)置于100mL的三颈烧瓶中，在N2保护下，抽真空5-60分钟，充N2约10-60分钟；加入5-15mL的CH2Cl2和5-15mL的CH3OH，回流反应6-24小时得到红色溶液；反应结束后，抽滤，用CH2Cl2和CH3OH洗涤后，干燥；用CH2Cl2/CH3OH(10：1，v/v)过硅胶柱，即可制得2-苯基喹啉3,3’-联吡啶二羧酸铱配合物。Weigh 2-phenylquinoline-iridium dichloro bridge complex (0.1-5g) and 2,2'-bipyridine-3,3'-dicarboxylic acid (0.2-10g) into a 100mL three-necked flask, Under the protection ofN2 , vacuumize for 5-60 minutes, fill withN2 for about 10-60 minutes; add 5-15mL ofCH2Cl2 and5-15mLof CH3OH, and reflux for 6-24 hours to obtain a red solution; After the reaction, filter with suction, wash with CH2 Cl2 and CH3 OH, and dry; use CH2 Cl2 /CH3 OH (10:1, v/v) to pass through a silica gel column to obtain 2-benzene Quinoline 3,3'-bipyridyl dicarboxylate iridium complexes.
步骤(1)中，2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的质量浓度为0.01mg/mL。In step (1), the mass concentration of the iridium complex of 2-phenylquinoline 3,3'-bipyridinedicarboxylate is 0.01 mg/mL.
步骤(2)中，醋酸钬的质量浓度为0.01mg/mL。In step (2), the mass concentration of holmium acetate is 0.01mg/mL.
2-苯基喹啉3,3’-联吡啶二羧酸铱配合物与聚乙烯吡咯烷酮、醋酸钬的质量比为0.001：0.1：0.001。The mass ratio of 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex to polyvinylpyrrolidone and holmium acetate is 0.001:0.1:0.001.
本实施例制得的超声/磁共振双模式造影剂用于超声造影成像及磁共振造影成像。The ultrasound/magnetic resonance dual-mode contrast agent prepared in this example is used for ultrasound contrast imaging and magnetic resonance contrast imaging.
实施例8：Embodiment 8:
本实施例超声/磁共振双模式造影剂，该造影剂为表面采用聚乙烯吡咯烷酮修饰的配位聚合物纳米粒子造影剂，该配位聚合物纳米粒子造影剂内部具有空腔结构，并且所述的配位聚合物纳米粒子造影剂中还掺杂有稀土元素Ir及Ho。In this embodiment, the ultrasound/magnetic resonance dual-mode contrast agent is a coordination polymer nanoparticle contrast agent whose surface is modified with polyvinylpyrrolidone. The coordination polymer nanoparticle contrast agent has a cavity structure inside, and the The coordination polymer nanoparticle contrast agent is also doped with rare earth elements Ir and Ho.
其中，配位聚合物纳米粒子造影剂的化学结构式为：Wherein, the chemical structural formula of the coordination polymer nanoparticle contrast agent is:
本实施例中，配位聚合物纳米粒子造影剂中，稀土元素Ir的质量百分含量为25％，稀土元素Ho的质量百分含量为20％。配位聚合物纳米粒子造影剂的粒径为400nm，壁厚为60nm。In this embodiment, in the coordination polymer nanoparticle contrast agent, the mass percentage of the rare earth element Ir is 25%, and the mass percentage of the rare earth element Ho is 20%. The particle diameter of the coordination polymer nanoparticle contrast agent is 400nm, and the wall thickness is 60nm.
制备方法具体包括以下步骤：The preparation method specifically comprises the following steps:
(1)配制2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液；(1) prepare the DMSO solution of 2-phenylquinoline 3,3'-bipyridyl iridium dicarboxylate complex;
(2)配制醋酸钬的DMSO溶液；(2) prepare the DMSO solution of holmium acetate;
(3)向步骤(1)的溶液中加入聚乙烯吡咯烷酮，搅拌混合均匀，并升温至120℃，恒温1h；(3) Add polyvinylpyrrolidone to the solution in step (1), stir and mix evenly, and raise the temperature to 120°C, and keep the temperature constant for 1h;
(4)再加入步骤(2)配制的醋酸钬的DMSO溶液，反应24h，反应结束后，用去离子水透析10h，离心，即制得所述的双模式造影剂。(4) Add the DMSO solution of holmium acetate prepared in step (2) and react for 24 hours. After the reaction, dialyze with deionized water for 10 hours and centrifuge to obtain the dual-mode contrast agent.
本实施例中，2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的合成方法如下：In this example, the synthesis method of 2-phenylquinoline 3,3'-bipyridyl iridium dicarboxylate complex is as follows:
称取2-苯基喹啉铱二氯桥配合物(0.1-5g)和2,2’-联吡啶-3,3’-二羧酸(0.2-10g)置于100mL的三颈烧瓶中，在N2保护下，抽真空5-60分钟，充N2约10-60分钟；加入5-15mL的CH2Cl2和5-15mL的CH3OH，回流反应6-24小时得到红色溶液；反应结束后，抽滤，用CH2Cl2和CH3OH洗涤后，干燥；用CH2Cl2/CH3OH(10：1，v/v)过硅胶柱，即可制得2-苯基喹啉3,3’-联吡啶二羧酸铱配合物。Weigh 2-phenylquinoline-iridium dichloro bridge complex (0.1-5g) and 2,2'-bipyridine-3,3'-dicarboxylic acid (0.2-10g) into a 100mL three-necked flask, Under the protection ofN2 , vacuumize for 5-60 minutes, fill withN2 for about 10-60 minutes; add 5-15mL ofCH2Cl2 and5-15mLof CH3OH, and reflux for 6-24 hours to obtain a red solution; After the reaction, filter with suction, wash with CH2 Cl2 and CH3 OH, and dry; use CH2 Cl2 /CH3 OH (10:1, v/v) to pass through a silica gel column to obtain 2-benzene Quinoline 3,3'-bipyridyl dicarboxylate iridium complexes.
步骤(1)中，2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的质量浓度为2mg/mL。In step (1), the mass concentration of the iridium complex of 2-phenylquinoline 3,3'-bipyridinedicarboxylate is 2 mg/mL.
步骤(2)中，醋酸钬的质量浓度为2mg/mL。In step (2), the mass concentration of holmium acetate is 2mg/mL.
2-苯基喹啉3,3’-联吡啶二羧酸铱配合物与聚乙烯吡咯烷酮、醋酸钬的质量比为10：1：10。The mass ratio of 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex to polyvinylpyrrolidone and holmium acetate is 10:1:10.
本实施例制得的超声/磁共振双模式造影剂用于超声造影成像及磁共振造影成像。The ultrasound/magnetic resonance dual-mode contrast agent prepared in this example is used for ultrasound contrast imaging and magnetic resonance contrast imaging.
实施例9：Embodiment 9:
本实施例超声/磁共振双模式造影剂，该造影剂为表面采用聚乙烯吡咯烷酮修饰的配位聚合物纳米粒子造影剂，该配位聚合物纳米粒子造影剂内部具有空腔结构，并且所述的配位聚合物纳米粒子造影剂中还掺杂有稀土元素Ir及Ho。In this embodiment, the ultrasound/magnetic resonance dual-mode contrast agent is a coordination polymer nanoparticle contrast agent whose surface is modified with polyvinylpyrrolidone. The coordination polymer nanoparticle contrast agent has a cavity structure inside, and the The coordination polymer nanoparticle contrast agent is also doped with rare earth elements Ir and Ho.
其中，配位聚合物纳米粒子造影剂的化学结构式为：Wherein, the chemical structural formula of the coordination polymer nanoparticle contrast agent is:
本实施例中，配位聚合物纳米粒子造影剂中，稀土元素Ir的质量百分含量为30％，稀土元素Ho的质量百分含量为25％。配位聚合物纳米粒子造影剂的粒径为500nm，壁厚为80nm。In this embodiment, in the coordination polymer nanoparticle contrast agent, the mass percentage of the rare earth element Ir is 30%, and the mass percentage of the rare earth element Ho is 25%. The particle diameter of the coordination polymer nanoparticle contrast agent is 500nm, and the wall thickness is 80nm.
制备方法具体包括以下步骤：The preparation method specifically comprises the following steps:
(1)配制2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的DMSO溶液；(1) prepare the DMSO solution of 2-phenylquinoline 3,3'-bipyridyl iridium dicarboxylate complex;
(2)配制醋酸钬的DMSO溶液；(2) prepare the DMSO solution of holmium acetate;
(3)向步骤(1)的溶液中加入聚乙烯吡咯烷酮，搅拌混合均匀，并升温至165℃，恒温0.5h；(3) Add polyvinylpyrrolidone to the solution in step (1), stir and mix evenly, and raise the temperature to 165°C, and keep the temperature constant for 0.5h;
(4)再加入步骤(2)配制的醋酸钬的DMSO溶液，反应12h，反应结束后，用去离子水透析12h，离心，即制得所述的双模式造影剂。(4) Add the DMSO solution of holmium acetate prepared in step (2) and react for 12 hours. After the reaction, dialyze with deionized water for 12 hours and centrifuge to obtain the dual-mode contrast agent.
本实施例中，2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的合成方法如下：In this example, the synthesis method of the iridium complex of 2-phenylquinoline 3,3'-bipyridinedicarboxylate is as follows:
称取2-苯基喹啉铱二氯桥配合物(0.1-5g)和2,2’-联吡啶-3,3’-二羧酸(0.2-10g)置于100mL的三颈烧瓶中，在N2保护下，抽真空5-60分钟，充N2约10-60分钟；加入5-15mL的CH2Cl2和5-15mL的CH3OH，回流反应6-24小时得到红色溶液；反应结束后，抽滤，用CH2Cl2和CH3OH洗涤后，干燥；用CH2Cl2/CH3OH(10：1，v/v)过硅胶柱，即可制得2-苯基喹啉3,3’-联吡啶二羧酸铱配合物。Weigh 2-phenylquinoline-iridium dichloro bridge complex (0.1-5g) and 2,2'-bipyridine-3,3'-dicarboxylic acid (0.2-10g) into a 100mL three-necked flask, Under the protection ofN2 , vacuumize for 5-60 minutes, fill withN2 for about 10-60 minutes; add 5-15mL ofCH2Cl2 and5-15mLof CH3OH, and reflux for 6-24 hours to obtain a red solution; After the reaction, filter with suction, wash with CH2 Cl2 and CH3 OH, and dry; use CH2 Cl2 /CH3 OH (10:1, v/v) to pass through a silica gel column to obtain 2-benzene Quinoline 3,3'-bipyridyl dicarboxylate iridium complexes.
步骤(1)中，2-苯基喹啉3,3’-联吡啶二羧酸铱配合物的质量浓度为8mg/mL。In step (1), the mass concentration of the iridium complex of 2-phenylquinoline 3,3'-bipyridinedicarboxylate is 8 mg/mL.
步骤(2)中，醋酸钬的质量浓度为8mg/mL。In step (2), the mass concentration of holmium acetate is 8mg/mL.
2-苯基喹啉3,3’-联吡啶二羧酸铱配合物与聚乙烯吡咯烷酮、醋酸钬的质量比为200：35：200。The mass ratio of 2-phenylquinoline 3,3'-bipyridinedicarboxylate iridium complex to polyvinylpyrrolidone and holmium acetate is 200:35:200.
本实施例制得的超声/磁共振双模式造影剂用于超声造影成像及磁共振造影成像。The ultrasound/magnetic resonance dual-mode contrast agent prepared in this example is used for ultrasound contrast imaging and magnetic resonance contrast imaging.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106188149B (en)* | 2016-07-05 | 2019-03-22 | 上海师范大学 | A kind of near-infrared metal iridium complex and its preparation method and application |
| CN106310259B (en)* | 2016-10-12 | 2019-05-07 | 上海师范大学 | A kind of multifunctional nanocomposite material and its preparation method and application |
| CN107854695A (en)* | 2017-05-08 | 2018-03-30 | 上海师范大学 | The rare-earth metal doped hollow silica nanoparticle of targeting modification and its application |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030003055A1 (en)* | 1989-12-22 | 2003-01-02 | Unger Evan C. | Methods of preparing gaseous precursor-filled microspheres |
| US20140140934A1 (en)* | 2012-11-21 | 2014-05-22 | Korea Institute Of Science And Technology | Liver tumor-targeting ultrasound contrast agent and method for preparing the same |
| CN104787054A (en)* | 2015-04-28 | 2015-07-22 | 北京中索国游索道工程技术有限公司 | Detachable rope clip |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19640981A1 (en)* | 1996-10-04 | 1998-04-16 | Asea Brown Boveri | Rogowski coil |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030003055A1 (en)* | 1989-12-22 | 2003-01-02 | Unger Evan C. | Methods of preparing gaseous precursor-filled microspheres |
| US20140140934A1 (en)* | 2012-11-21 | 2014-05-22 | Korea Institute Of Science And Technology | Liver tumor-targeting ultrasound contrast agent and method for preparing the same |
| CN104787054A (en)* | 2015-04-28 | 2015-07-22 | 北京中索国游索道工程技术有限公司 | Detachable rope clip |
| Title |
|---|
| Effects of Nanoparticle Size on Cellular Uptake and Liver MRI with Polyvinylpyrrolidone-Coated Iron Oxide Nanoparticles;Jing Huang,et al;《ACS NANO》;20101202(第12期);第7151-7160页* |
| Publication number | Publication date |
|---|---|
| CN105288667A (en) | 2016-02-03 |
| Publication | Publication Date | Title |
|---|---|---|
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