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Conjugated carbon-iodine polymer and preparation thereof, and application of conjugated carbon-iodine polymer in preparation of positioning marker

A polymer and marker technology, which is used in the preparation of X-ray contrast agents, preparations for in vivo experiments, and pharmaceutical formulations, etc. Stability and other issues to achieve the effect of improving CT imaging quality, meeting clinical needs, and making up for defects and deficiencies

Active Publication Date: 2022-03-08
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The present invention solves the technical problems of low imaging quality, unstable relative position, and poor biocompatibility of the imaging markers in the prior art. Provided is a conjugated polymer containing a polydiacetylene (PDA) backbone but with only iodine atom substituents, as well as methods of synthesis and use in label-guided precision surgical resection and radiation therapy in vivo

Method used

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  • Conjugated carbon-iodine polymer and preparation thereof, and application of conjugated carbon-iodine polymer in preparation of positioning marker
  • Conjugated carbon-iodine polymer and preparation thereof, and application of conjugated carbon-iodine polymer in preparation of positioning marker
  • Conjugated carbon-iodine polymer and preparation thereof, and application of conjugated carbon-iodine polymer in preparation of positioning marker

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Embodiment 1

[0053] Example 1: Polymer design and CT imaging performance characterization

[0054]

[0055] According to the ligand-receptor co-crystal polymerization synthesis method, the present invention cultures single crystals of PIDA monomer and ligand E3 in methanol, and can realize topological polymerization at room temperature to obtain PIDA-E3 co-crystal ( figure 1 in a). The three-dimensional structure between the conjugated polymer PIDA and the small molecule ligand E3 was confirmed by single crystal X-ray diffraction analysis ( figure 1 in b). The distance between the iodine atom on the side chain of PIDA and the nitrogen atom of the pyridyl group at the end of the ligand E3 is 2.925 angstroms, and the two interact through a strong halogen bond. The small molecule E3 itself is arranged in an orderly manner through the hydrogen bonds between the oxalic acid amide structures, and the distance between the repeating units on PIDA is the same as that of 4.957 angstroms. The ...

Embodiment 2

[0062] Example 2: Multiple Local Labeling in Animals

[0063] In order to verify whether the super-strong CT imaging effect of PIDA can be pushed to practical application, the present invention injects PIDA dispersion and iohexol with the same iodine content locally into rat leg muscles respectively under the guidance of CT. For effective CT labeling, the CT signal intensity should be more than 2 times that of the background tissue. The background CT signal of rat muscle tissue is about 50 HU, and the CT marker signal intensity exceeding 100 HU can be regarded as an effective CT marker. The results showed that the intramuscular injection in the PIDA group showed a significant CT enhancement effect. Considering the effective time of the overall operation before the clinical operation and during the operation, it was found that PIDA always maintained a strong CT enhancement effect within 6 hours ( Figure 4 in a). In the corresponding intramuscular injection of the iohexol gro...

Embodiment 3

[0067] Example 3: PIDA Markers for CyberKnife Therapy

[0068] In addition to surgical resection of tumors, radiation is also an important means of tumor treatment, and the most cutting-edge precision radiation therapy—cyberknife therapy relies on accurate CT positioning of implanted markers ( Figure 10 in a). Although gold simple substance markers commonly used in clinical practice can meet the requirements of strong CT signal and relatively stable position of CT positioning markers, they can easily cause local edema, which in turn leads to positioning deviation. Poor biocompatibility, permanent retention in the body is difficult to degrade. CT metal artifacts are severe (a in Figure 7), which affects the quality of CT imaging and the planning of subsequent radiation dose distribution maps. Such problems reduce the curative effect of CyberKnife and limit its further popularization and use. Based on this, the present invention replaces gold markers with PIDA solid fibers, ...

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Abstract

The invention relates to a conjugated carbon-iodine polymer, preparation thereof and application of the conjugated carbon-iodine polymer in preparation of a positioning marker, and belongs to the technical field of imaging markers. According to the brand-new imaging marker based on the conjugated carbon-iodine polymer disclosed by the invention, due to the conjugated structure, the polymer has very strong absorption in a visible light region, and the iodine content up to 84.1% corresponds to the superstrong imaging capability of the polymer. In the tumor operation process, based on double guidance of polymer image marking and naked eye observation, the marking can better assist in determining the cutting edge of the tumor, so that accurate cutting of the tumor is achieved, and damage to surrounding normal tissue is reduced as much as possible. In the tumor cyber knife treatment process, the polymer can replace a clinical gold mark to provide ray marking guidance, the ray imaging quality and more accurate radiation dose distribution are improved due to no metal artifacts, the relative stability of the marking position is improved due to good biocompatibility, and the radiotherapy side effect can be further reduced.

Description

technical field [0001] The invention belongs to the technical field of imaging markers, and more specifically relates to a conjugated carbon-iodide polymer and its preparation and application for preparing positioning markers. Background technique [0002] Cancer is a leading cause of morbidity and mortality worldwide. Considering the high risk and high mortality rate of cancer, researchers around the world have been working hard to develop more precise and rapid diagnosis and treatment methods to fight cancer. In clinical cancer treatment, most cancer treatment methods (such as chemotherapy, radiotherapy and surgery) are partially successful, but they also have certain limitations, and they often damage the surrounding healthy tissue, which ultimately affects the patient's survival period, tumor Precision therapy is considered to be an important direction for future development. Although there are many reports of targeted drugs in chemotherapy, the problem of systemic tox...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G61/04A61K49/04
CPCC08G61/04A61K49/0442C08G2261/11C08G2261/18C08G2261/3328C08G2261/3327C08G2261/146Y02E10/549C08L65/00C09D165/00C08G2261/12C08G2261/1432C08G2261/3422C08G2261/94A61K49/0461
Inventor 罗亮殷明明刘小明孟凡玲
Owner HUAZHONG UNIV OF SCI & TECH
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