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Platinum-containing compound and composition and application thereof

A platinum compound and composition technology, applied in the field of tumor treatment, can solve the problems of poor effect, easy generation of drug resistance, hidden dangers of adverse reactions, etc., and achieve the effects of expanding the drug spectrum, improving the poor therapeutic effect and improving the prognosis.

Active Publication Date: 2021-11-30
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In view of the above-mentioned problems and deficiencies, the present invention provides a platinum-containing compound and its composition and application, to solve the long-term use of cisplatin in the prior art to treat lung cancer The existing problems are poor effect, easy to produce drug resistance, and many hidden dangers of adverse reactions

Method used

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  • Platinum-containing compound and composition and application thereof
  • Platinum-containing compound and composition and application thereof
  • Platinum-containing compound and composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1 Cell Killing Experiment in Vitro

[0045] (1) H1975, H23, PC9, H1299, H460 and H2228 cells in the logarithmic growth phase were seeded in 96-well plates at a certain density (3000-5000 / well);

[0046] (2) After 24 hours, the old medium was discarded, and the cells were treated with medium containing different concentrations of drugs; the drugs used were the above-mentioned compound of formula II (Bi-lagand) and compound of formula III (Tri-ligand) , cisplatin (DDP), disulfiram (DSF) and a mixture of DDP and DSF (the molar concentration ratio of the two is 1:1), the drug concentration gradients are 100 μM, 20 μM, 4 μM, 0.8 μM, 0.16 μM, 0.032 μM , 0.0064μM, 0.00128μM and 0μM, and set the blank group without inoculating cells;

[0047] (3) After culturing for 48 hours, add 20 μL of 5 mg / mL MTT solution to each well, place in a 37°C incubator and incubate in the dark for 4 hours, discard the medium carefully, try not to absorb the formazan at the bottom of the we...

Embodiment 2

[0053] Embodiment 2 combined drug experiment

[0054] (1) A549 and H2228 cells in the logarithmic growth phase were inoculated in a 96-well plate at a certain density (3000-5000 / well);

[0055] (2) After 24 hours, the old medium was discarded, and the cells were treated with medium containing different concentrations of drugs; the drugs used were the compound of formula III (Tri-ligand), cisplatin (DDP) and Tri-ligand and DDP (the molar concentration ratio of the two is 1:1), the drug concentration gradients are 100 μM, 20 μM, 4 μM, 0.8 μM, 0.16 μM, 0.032 μM, 0.0064 μM, 0.00128 μM and 0 μM, and the blank group is not inoculated cell;

[0056] (3) After culturing for 48 hours, add 20 μL of 5 mg / mL MTT solution to each well, place in a 37°C incubator and incubate in the dark for 4 hours, discard the medium carefully, try not to absorb the formazan at the bottom of the well, and add DMSO to dissolve the formazan. Zan was dissolved, placed on a shaker and shaken at a low speed f...

Embodiment 3

[0059] Example 3 Effects of platinum-containing compounds on the ability to form different NSCLC clones

[0060] (1) Spread about 500 to 2000 cells (H460 and HCC827) in each well of a six-well plate, and choose different densities according to different experimental purposes;

[0061] (2) Appropriately treat the cells after 24 hours (drugs or irradiate 12 hours after adding drugs), continue to culture for 10 to 14 days, and stop when a single cell clone grows to a clone greater than 50 cells to cultivate;

[0062] (3) Remove the medium supernatant, wash once with 1× PBS solution, stain with 0.5% crystal violet methanol solution, observe the number of clones formed in each group, take pictures and statistics, and calculate the clone formation rate: clone formation Rate = (number of plated clones / total number of plated cells) × 100%.

[0063] The result is as follows figure 2 shown. The results show that the platinum-containing compound of the present invention can produce ...

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Abstract

The invention provides a pharmaceutical composition for treating cancer, especially lung cancer. The pharmaceutical composition comprises a platinum-containing compound. Through a large number of long-term researches, it is found that the platinum-containing compound, especially Tri-ligand, can generate a remarkable growth inhibition effect on lung cancer cells in vivo and in vitro; and the effect of the compound is obviously superior to that of a drug (cisplatin) suggested by a first-line treatment scheme for clinically treating lung cancer, even a DDP+DSF combined medication scheme which is newly researched and used for improving the drug resistance of the cisplatin, and besides, the in-vivo safety shown by Tri-ligand is also superior to that of the DDP+DSF combined medication scheme. Therefore, a new treatment strategy is provided for the lung cancer, especially non-small cell lung cancer, the medication spectrum of the lung cancer can be effectively expanded, and the current situations that the first-line treatment medicine cisplatin for the lung cancer is poor in effects, prone to drug resistance and the like are improved. The invention plays an important role in improving the prognosis of lung cancer, and has very important clinical significance and social significance.

Description

technical field [0001] The invention belongs to the technical field of tumor treatment, and specifically relates to a platinum-containing compound and its composition and application. Background technique [0002] Lung cancer is a common malignant tumor of the respiratory system, and it is one of the most common tumors with the highest discovery rate in the world. In the past 50 years, many countries have reported that the incidence and mortality of lung cancer have increased significantly. The incidence and mortality of lung cancer in men account for the first of all malignant tumors, and the incidence and mortality of lung cancer occupy the second place in women. The etiology of lung cancer is still not completely clear. [0003] Clinically, there are mainly chemotherapy, radiotherapy, and surgery for lung cancer. Chemotherapy is the most common treatment for lung cancer. More than 90% of lung cancers require chemotherapy. The curative effect of chemotherapy on small c...

Claims

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Application Information

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IPC IPC(8): A61K31/282A61K45/06A61P35/00
CPCA61K31/282A61K45/06A61P35/00A61K2300/00
Inventor 刘然义袁雪霞岳欣段有发
Owner SUN YAT SEN UNIV CANCER CENT
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