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Fluorescence specific nanometer iron oxide hybrid dispersion liquid for cancer metastatic lymph node tracing as well as preparation method and purpose of fluorescence specific nanometer iron oxide hybrid dispersion liquid

A nano-iron oxide and hybrid technology, which is applied in the direction of dispersion liquid delivery, preparations for in vivo tests, luminescent/biological dyeing preparations, etc., can solve the problems of lymph node omission, insufficient free iron ions, false negatives, etc., and achieve simple experiments , Improve water solubility, save the effect of cumbersome operations

Pending Publication Date: 2018-06-05
王亚楠
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, clinical experiments have shown that oral or intravenous ALA-induced porphyrin fluorescence is still limited to isolated specimens for the diagnosis of human gastrointestinal cancer metastatic lymph nodes. Although the specificity is high, the sensitivity is not satisfactory, and false positives and false positives are prone to occur. negative result
The inventors analyzed the reasons as follows: (1) Since ALA-induced autofluorescence does not have the effect of visual tracer under white light, the use of fluorescence detectors in intra-abdominal living tissues cannot be targeted. In order to avoid missing lymph nodes, we can only choose Fluorescent detection of isolated specimens
(2) Although oral or intravenous administration of exogenous ALA can cause the accumulation of protoporphyrin in the lymph nodes and produce autofluorescence with an intensity 10 times higher than that of normal cells, but at the same time, the fat or connective tissue around the lymph nodes will also be exposed to protoporphyrin due to the increased concentration of ALA. The relative lack of free iron ions necessary for the continued metabolism of phyllophyrin to form heme leads to the accumulation of protoporphyrin and autofluorescence, which affects the observation of porphyrin fluorescence in tumor metastatic lymph nodes, resulting in false positive or false negative results
(3) Due to the limitation of ALA concentration in the lymph nodes through the systemic blood circulation after oral and intravenous administration of exogenous ALA, it is almost impossible for metastatic lesions smaller than 200 μm in tiny lymph nodes to produce sufficient autologous porphyrin fluorescence to detect, resulting in false negative results

Method used

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  • Fluorescence specific nanometer iron oxide hybrid dispersion liquid for cancer metastatic lymph node tracing as well as preparation method and purpose of fluorescence specific nanometer iron oxide hybrid dispersion liquid
  • Fluorescence specific nanometer iron oxide hybrid dispersion liquid for cancer metastatic lymph node tracing as well as preparation method and purpose of fluorescence specific nanometer iron oxide hybrid dispersion liquid
  • Fluorescence specific nanometer iron oxide hybrid dispersion liquid for cancer metastatic lymph node tracing as well as preparation method and purpose of fluorescence specific nanometer iron oxide hybrid dispersion liquid

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Embodiment 1

[0037] Such as figure 1 , a fluorescence-specific nano-iron oxide hybrid dispersion (5ALA-Dex-SPIO) for cancer metastatic lymph node tracking, including dextran derivatives, iron oxide particles and water, the dextran derivatives and Iron oxide particles are combined to form nano-iron oxide hybrids, which are uniformly dispersed in water; the nano-iron oxide hybrids are prepared by co-precipitation of dextran derivatives and iron salts; the dextran The sugar derivative is prepared by reacting 5-aminolevulinic acid (5ALA) with oxidized dextran through Schiff base; the diameter of the nano iron oxide hybrid is between 100-180nm.

Embodiment 2

[0039] A use of a fluorescence-specific nano-iron oxide hybrid dispersion liquid for cancer metastasis lymph node tracing, this embodiment adopts the fluorescence-specific nano-iron oxide hybrid dispersion for cancer metastasis lymph node tracing described in Example 1 Liquid, the fluorescence-specific nano-iron oxide hybrid dispersion liquid for cancer metastasis lymph node tracking is used for preoperative and intraoperative local injection of solid malignant tumors such as gastrointestinal cancer, breast cancer, thyroid cancer, etc. When used, it is used for local injection around solid malignant tumor tissues such as gastrointestinal cancer mucosa or subserosa, breast cancer, and thyroid cancer.

Embodiment 3

[0041] A method for preparing a fluorescence-specific nano-iron oxide hybrid dispersion liquid for cancer metastasis lymph node tracing, comprising the following steps,

[0042] S1: Synthesis of oxidized dextran:

[0043] Weigh 5.0 g of dextran (molecular weight 10KDa) (Dextran) and dissolve it in 400 mL deionized water, then add sodium periodate (1.25 g dissolved in 100 mL deionized water) (NaIO 4 ), react at room temperature in the dark for 24 h, add 2 mL of ethylene glycol dropwise to deactivate unreacted sodium periodate, continue stirring for 1 h, put the reaction product in a cellulose dialysis bag with a molecular weight cut-off of 10,000, and use Deionized water was dialyzed for 3 days and lyophilized to obtain oxidized dextran.

[0044] S2: Synthesis of Dextran Derivatives:

[0045] Weigh 0.1 g of oxidized dextran and dissolve it in a phosphate buffer with pH 8.0, add 0.01 g of 5-aminolevulinic acid hydrochloride, react in the dark for 24 hours, dialyze and freeze-d...

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Abstract

The invention relates to the field of medical preparations, in particular to fluorescence specific nanometer iron oxide hybrid dispersion liquid for cancer metastatic lymph node tracing as well as a preparation method and a purpose of the fluorescence specific nanometer iron oxide hybrid dispersion liquid. The fluorescence specific nanometer iron oxide hybrid dispersion liquid for cancer metastatic lymph node tracing comprises a dextran derivative, iron oxide particles and water; the dextran derivative is combined with the iron oxide particles to form a nanometer iron oxide hybrid which is uniformly dispersed in the water and is prepared from the dextran derivative and ferric salt through a coprecipitation method; and the dextran derivative is prepared from 5-aminolevulinic acid and oxidized dextran through Schiff base reaction. The prepared fluorescence specific nanometer iron oxide hybrid dispersion liquid is hopeful to be applied to evaluation of gastrointestinal cancer metastatic lymph nodes and can be coupled to an anti-tumor drug through function derivatization of dextran so as to realize the purpose of diagnosis and treatment integration.

Description

technical field [0001] The invention relates to the field of medical tracer diagnostic reagents, in particular to a fluorescence-specific nano-iron oxide hybrid dispersion liquid for cancer metastasis lymph node tracer and its preparation method and application. Background technique [0002] Gastrointestinal cancer is one of the most lethal tumors worldwide. my country is a high-incidence area of ​​gastrointestinal cancer. Gastric cancer and colorectal cancer are the third and fourth leading causes of cancer death, with mortality rates of 17.96 / 100,000 and 12.59 / 100,000, respectively. Lymph node metastasis is the main way of metastasis of gastrointestinal cancer, and the evaluation of its metastasis is the most important basis for deciding the operation method, accurate pathological staging, and formulating adjuvant treatment plan. Doctors often use imaging methods to evaluate the metastatic lymph nodes before surgery. Such as B-ultrasound, CT and magnetic resonance method...

Claims

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Application Information

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IPC IPC(8): A61K49/00
CPCA61K49/0021A61K49/0054A61K49/006A61K49/0076
Inventor 王亚楠周海鹏傅超萍李国新张黎明邓海军
Owner 王亚楠
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