Iridium complex-based double-metal-center radiodynamic drug and preparation method thereof

An iridium complex and kinetic technology, applied in the field of medicine, can solve the problems of limited enhancement effect and no large-scale clinical application, and achieve the effects of reducing the attenuation length, improving the energy transfer efficiency, and increasing the attenuation coefficient.

Pending Publication Date: 2022-03-01
上海市质子重离子临床技术研发中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the past, it was believed that radiotherapy sensitizing drugs fit the T1PE mechanism of drugs directly producing ROS under X-rays, and every increase of 1wt% (gold / water) would have a radiotherapy enhancement effect of 1.4 times. This enhancement effect is very limited, so there is no major clinical application at scale

Method used

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  • Iridium complex-based double-metal-center radiodynamic drug and preparation method thereof
  • Iridium complex-based double-metal-center radiodynamic drug and preparation method thereof
  • Iridium complex-based double-metal-center radiodynamic drug and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] In this embodiment, R1 is selected from phenyl, X is selected from nitrogen atom, R2 is selected from methyl group; M is selected from holmium(III) ion.

[0033] When R1 is selected from phenyl, X is selected from nitrogen atom, and R2 is selected from methyl group, the radiodynamic drug tetrakis[bis(2,3-diphenylquinoxaline)·2,2'- Bipyridine-4,4'-dicarboxylate iridium(III)]·bis(acetic acid)diholmium(III)(Ir-M-1).

[0034] Its synthetic chemical formula is as figure 1 Shown, concrete its preparation process is:

[0035] 1. Preparation of intermediate bridged chloroiridium complex (Ir-1):

[0036] 2,3-diphenylquinoxaline (310.6mg, 1.1mmol) and IrCl 3 Hydrate (60% Ir, 160mg, 0.5mmol) was added to 5mL of H 2 O and 15mL of 2-methoxyethanol in a mixed solvent, then reflux and stir for 24h under the protection of an inert gas (argon). After cooling down to room temperature, add 5 mL of H 2 O, the ice bath was further cooled until a large amount of brown precipitates were...

Embodiment 2

[0042] Verification of X-ray absorption effect of radiodynamic drug (Ir-M-1) in solid state:

[0043] The Ir-2 and Ir-M-1 solid powders described in Example 1 are respectively placed in a 1mL centrifuge tube, and the emission spectrum at 365nm is tested on Edinburgh FLS 980 under the irradiation of X-rays (0.05Gy / h) .

[0044] figure 2 Represents the X-ray emission spectrum of the radiodynamic drug (Ir-M-1) with a double metal center described in Example 1 of the present invention and the iridium complex (Ir-2) that does not form a double metal center complex under solid .

[0045] In the figure: Ir-M-1 can be directly excited by X-rays in the solid state and emit red fluorescence, while Ir-2 hardly observes fluorescence emission;

[0046] From the above results, it can be seen that the bimetallic center structure involved in the present invention has better absorption of X-rays and higher energy transfer efficiency.

Embodiment 3

[0048] Verification of the Relative Generation of Hydroxyl Free Radicals (·OH) in Radiokinetic Drug (Ir-M-1) Aqueous Solutions under X-ray Irradiation:

[0049] 1. Prepare the Ir-2 and Ir-M-1 described in Example 1 into 1 mg / mL aqueous solution respectively, then add methylene blue with a final concentration of 0.25 mg / mL in the solution as a hydroxyl radical indicator, and use ultraviolet A spectrometer measures the absorbance of these solutions at 664 nm.

[0050] 2. After exposing the above solution to X-rays (0.25Gy), test the absorbance of the solution at 664nm again, and calculate the degradation rate of methylene blue.

[0051] like image 3 It means that the double metal center radiodynamic drug (Ir-M-1) described in Example 1 of the present invention and the iridium complex (Ir-2) that does not form a double metal center complex are irradiated by X-rays in an aqueous solution of the same concentration The relative generation content of hydroxyl radicals (·OH) is sho...

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Abstract

The invention discloses a bimetallic-center radiodynamic drug based on an iridium complex and a preparation method of the bimetallic-center radiodynamic drug, and aims to solve the major problems that the energy utilization efficiency of existing radiotherapy is low, and the structure and the function of existing radiodynamic drugs are not perfect. Research and development of radiodynamic drugs with high X-ray absorption, high energy transfer efficiency and high ROS generation capability are extremely urgent, and particularly, new drugs with proprietary intellectual property rights in China and containing high Z elements and photosensitizers in molecules are developed, so that the iridium complex-based bimetal center radiodynamic drugs are provided; the compound is used for enhancing the curative effect of radiotherapy, can enhance X-ray absorption of a focus, and can enhance energy deposition around the medicine through a T2PE mechanism, so that a higher radiodynamic curative effect is achieved.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to a radiodynamic drug based on a bimetallic center of an iridium complex. Background technique [0002] On a global scale, radiation therapy has provided great help to human beings against malignant tumors. Among the many high-energy particle rays, the traditional X-ray is still the most used at present. As a source of ionizing radiation, X-rays have been widely used in clinical treatment to improve patient survival due to their deep penetration and high radiation energy. [0003] However, due to the weak absorption and scattering of X-rays by human lesions, most of the X-ray energy passes out of the body or is absorbed by normal tissues. At present, the mainstream way to improve the utilization rate of X-rays is to use radiotherapy sensitizing drugs of high-Z media, for example, the use of nano-medicines containing high-Z atoms such as bismuth, gold, and platinum can enhance th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F19/00A61K41/00A61P35/00
CPCC07F15/0033A61K41/0038A61K41/0057A61P35/00
Inventor 孙筠邓勇
Owner 上海市质子重离子临床技术研发中心
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