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Application of 5-aminolevulinic acid and iron chelating agents in preparing anti-tumor combined drug

A technology of aminolevulinic acid and anti-tumor drugs, which is applied in the field of preparation of anti-tumor drugs, can solve problems such as limited treatment depth, limited photodynamic effect, and insufficient protoporphyrin concentration, so as to improve curative effect, inhibit growth, and promote tumor growth. The effect of apoptosis

Inactive Publication Date: 2019-05-31
TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In the clinical application of 5-aminolevulinic acid, it was found that in addition to the limited depth of treatment, the specificity and sensitivity of diagnosis and treatment were also insufficient, mainly because of the generation of 5-aminolevulinic acid in deep tissues or inside the tumor after administration. Insufficient porphyrin concentration and uneven distribution lead to limited photodynamic effect

Method used

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  • Application of 5-aminolevulinic acid and iron chelating agents in preparing anti-tumor combined drug
  • Application of 5-aminolevulinic acid and iron chelating agents in preparing anti-tumor combined drug
  • Application of 5-aminolevulinic acid and iron chelating agents in preparing anti-tumor combined drug

Examples

Experimental program
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Effect test

Embodiment 1

[0045] Example 1: The effects of 5-aminolevulinic acid or deferasirox and their combined use on the proliferation ability of human tongue cancer cells SCC-25 were detected by MTT assay

[0046] SCC-25 cells in the logarithmic growth phase were digested with 0.05% trypsin for 2 min, then digested with complete medium, centrifuged at 1000 r / min for 3 min, discarded the supernatant, added 9 mL of complete medium and gently blown to make the cells Single cell suspension, count the cells of this cell suspension, adjust the cell concentration to 2×10 4 The cell density of cells / ml was plated in 96-well plates, that is, 5-aminolevulinic acid group, deferasirox group, 5-aminolevulinic acid+deferasirox combined use group and negative control group. After 12 hours, the culture medium was discarded, replaced with serum-free DMEM, and then added with 20 μL per well. The final concentrations of each compound were 5-aminolevulinic acid: 25 μg / mL, deferasirox: 1 μg / mL, 5-aminolevulinic acid:...

Embodiment 2

[0048] Example 2: Detecting the effects of 5-aminolevulinic acid or deferasirox alone and in combination on protoporphyrin production in human tongue cancer cells SCC-25 by flow cytometry

[0049] SCC-25 cells in the logarithmic growth phase were digested with 0.05% trypsin for 2 min, then digested with complete medium, centrifuged at 1000 r / min for 3 min, discarded the supernatant, added 9 mL of complete medium and gently blown to make the cells Single cell suspension, count the cells of this cell suspension, adjust the cell concentration to 5×10 5 The cell density of cells / ml was spread in 60mm dishes, that is, 5-aminolevulinic acid group, deferasirox group, 5-aminolevulinic acid+deferasirox combined use group and negative control group. After 12 hours, the culture solution was discarded and washed once with PBS, and then added with serum-free DMEM, 150 μL per well. The final concentrations of each compound were 5-aminolevulinic acid: 25 μg / mL, deferasirox: 1 μg / mL , 5-amin...

Embodiment 3

[0051] Example 3: Detecting the effect of 5-aminolevulinic acid or deferasirox alone and in combination on the production of reactive oxygen species in human tongue cancer cells SCC-25 by flow cytometry

[0052] SCC-25 cells in the logarithmic growth phase were digested with 0.05% trypsin for 2 min, then digested with complete medium, centrifuged at 1000 r / min for 3 min, discarded the supernatant, added 9 mL of complete medium and gently blown to make the cells Single cell suspension, count the cells of this cell suspension, adjust the cell concentration to 5×10 5 The cell density per ml was spread in 60mm dishes, that is, 5-aminolevulinic acid group, deferasirox group, 5-aminolevulinic acid + deferasirox combined use group, negative control group and corresponding light Group. After 12 hours, the culture solution was discarded and washed once with PBS, and then added with serum-free DMEM, 150 μL per well. The final concentrations of each compound were 5-aminolevulinic acid: ...

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Abstract

The invention belongs to the technical field of anti-tumor drug preparation, and particularly relates to application of 5-aminolevulinic acid and iron chelating agents in preparing an anti-tumor combined drug. In a photodynamic therapy, through the combination of the 5-aminolevulinic acid and the iron chelating agents such as deferasirox and apoferritin, the generation of protoporphyrin and the production of reactive oxygen after illumination in tumor cells can be improved, the tumor growth is significantly inhibited, the 5-aminolevulinic acid and the iron chelating agents have an obvious synergistic effect, and the curative effect is better than that of the single component or the two components; through the combination of the iron chelating agents and the 5-aminolevulinic acid, the effect of the photodynamic therapy can be significantly enhanced, a new way is provided for tumor therapies, and a broad application prospect is brought in the field of medicine and pharmacology.

Description

technical field [0001] The invention belongs to the technical field of preparation of antitumor drugs, and in particular relates to the application of 5-aminolevulinic acid and iron chelating agent in the preparation of combined antitumor drugs. Background technique [0002] Combined drug therapy is one of the hot spots in the field of tumor treatment in recent years. A large number of clinical and experimental studies have proved that combined drug therapy has significant advantages in the prevention and rehabilitation of tumors. [0003] 5-aminolevulinic acid is a second-generation photosensitizer, an endogenous biochemical substance. In the mitochondria, glycine and succinyl CoA are condensed to generate 5-aminolevulinic acid under the catalysis of 5-aminolevulinic acid synthase. This reaction requires pyridoxal phosphate as a coenzyme, and 5-aminolevulinate synthase is the rate-limiting enzyme for heme synthesis (feedback inhibition by heme). The 5-aminolevulinic acid ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61P35/00A61K33/26
Inventor 王银松周平秦佳琪周策
Owner TIANJIN MEDICAL UNIV
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