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Application of amino-acid-modified metallofullerene water-soluble nanoparticles in preparation of tumor vascular disrupting agents

A metallofullerene and nanoparticle technology, used in antitumor drugs, medical preparations with non-active ingredients, radiotherapy, etc., to achieve the effects of no toxic side effects, reduced dosage, and strong integrity

Inactive Publication Date: 2017-05-10
BEIJING FUNAKANG BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Any other method of directly attacking tumor cells can only temporarily alleviate the disease to a large extent, and recurrence is difficult to avoid. This is also the limitation of current surgery, radiotherapy and chemotherapy.

Method used

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  • Application of amino-acid-modified metallofullerene water-soluble nanoparticles in preparation of tumor vascular disrupting agents
  • Application of amino-acid-modified metallofullerene water-soluble nanoparticles in preparation of tumor vascular disrupting agents
  • Application of amino-acid-modified metallofullerene water-soluble nanoparticles in preparation of tumor vascular disrupting agents

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1. Metallofullerylalanine nanoparticles Gd@C 82 (OH) 13 (NHCH 2 CH 2 COOH) 6 preparation of

[0055] Put about 10mg Gd@C 82 Add the solid to a 10ml single-necked bottle, add 6ml of β-alanine alkali solution with a mass fraction of NaOH of 14% (the molar ratio of β-alanine to NaOH is 1:2), and stir vigorously at 50°C for 1.5h, a black solid Gradually dissolved to generate a brown-black solution. A small amount of unreacted solid powder is removed by filtration, and the filtrate is dialyzed with a Mw=3500 dialysis bag to remove small molecular impurities, and the brown-black solution obtained after filtering with a 220nm microporous membrane is the amino acid-modified metallofulerene water-soluble nanometer Granular Gd@C 82 (OH) 13 (NHCH 2 CH 2 COOH) 6 (Also known as β-alanine modified metal fullerene nanoparticles, the structural formula is Gd@C 82 (OH) 13 (NHCH 2 CH 2 COOH) 6 , abbreviated as GF-Ala).

[0056] Table 1 Elemental analysis results ...

Embodiment 2

[0063] Example 2. Tumor treatment and effect comparison of metallofullerene nanoparticles modified by β-alanine under the action of radio frequency

[0064] 1. Establish the animal model of tumor-bearing mice:

[0065] Select 5-week-old female BALB / c mice with a body weight of 16.0-20.0 g, and subcutaneously inoculate 100 μL of 5×10 7 / ml of H22 liver cancer cells. After about 5-7 days of growth, the tumor size reaches 50-100mm 3 conduct experiment.

[0066] 2. Tumor treatment and comparative experiment of different drug effects

[0067] Comparative drug: water-soluble hydroxyl-modified Gd@C 82 Nanoparticles, the surface of which is modified with a large number of hydroxyl groups, such as figure 2 Shown is its thermogravimetric analysis TGA and DTG curves, combined with elemental analysis of C, H, and N content (C 36.95%, H 2.36%, N82 (OH) 26 .

[0068] Inject β-alanine derivatized GF-Ala and hydroxylated GF-OH (concentration: 1mmol / L, 2mg / kg) into tumor-bearing mice t...

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Abstract

The invention discloses application of amino-acid-modified metallofullerene water-soluble nanoparticles in the preparation of tumor vascular disrupting agents; the amino-acid-modified metallofullerene water-soluble nanoparticles have a structural general formula: metallofullerene-(OH)x(amino acid)y, wherein metallofullerene is metallic fullerene, with 0< / =x< / =50 and 0< / =y< / =50, and amino acid is a water-soluble amino acid. The tumor vascular disrupting agents prepared by applying the amino-acid-modified metallofullerene water-soluble nanoparticles to their preparation have higher biosafety, have zero toxic and side effects for normal biological tissues, are low in dosage and are good in treatment effect.

Description

technical field [0001] The invention relates to the application of amino acid-modified metal fullerene water-soluble nanoparticles in the preparation of tumor blood vessel blocking agents, and belongs to the field of nano-biomedicine. Background technique [0002] At present, cancer has become the second largest killer after cardiovascular disease, threatening human survival and health. Tumor growth and metastasis depend on the existence of vascular network, and tumor blood vessels are the nutrient channels and metastasis pathways of cancer cells. By selectively destroying the formed tumor vascular network to quickly cut off the tumor blood supply and induce ischemic necrosis of tumor cells, it is a practical and effective method to inhibit tumor growth and prevent metastasis. This concept was proposed by Juliana Denekamp in 1982. Correspondingly Drugs that are used are called vascular disrupting agents (VDAs). Any other method of directly attacking tumor cells can only te...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/44A61K9/51A61K47/62A61K47/54A61K47/69A61P35/00A61N5/00
CPCA61K33/44A61N5/00
Inventor 王春儒甄明明周悦
Owner BEIJING FUNAKANG BIOTECH CO LTD
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