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Silibinin and sorafenib-containing pharmaceutical composition and applications thereof

A technology of silibinin and composition, which is applied in the field of pharmaceutical compositions containing silybin and sorafenib, can solve the problems of combined drug use and no silybin, and achieve good synergy and bioavailability The effect of improving the degree of toxicity and small side effects

Active Publication Date: 2014-07-23
ZHONGXING PHARM CO LTD JIANGSU
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] At present, there is no report on the combination of silybin and sorafenib

Method used

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  • Silibinin and sorafenib-containing pharmaceutical composition and applications thereof
  • Silibinin and sorafenib-containing pharmaceutical composition and applications thereof
  • Silibinin and sorafenib-containing pharmaceutical composition and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1 The determination and IC of silybin and Sorafenib combined drug concentration 50 Determination.

[0024] In this example, the MTT method was used to analyze the drug sensitivity of HepG2 cells to silybin and sorafenib. HepG2 cells were treated with 1×10 4 / mL concentration was inoculated in a 96-well culture plate, 100 μL / well, and after culturing overnight, different concentrations of drugs or control solutions (20 μL per well) were added. Among them, silybin had 8 concentration gradients, respectively 10, 5 , 2.5, 1.25, 0.625, 0.3125, 0.1500 and 0.0750 (units are μmol / L); Sorafenib has 7 concentration gradients, respectively 10, 5, 2.5, 1.25, 0.625, 0.3125 and 0.1500 (units are μmol / L). Three replicate wells were set for each drug concentration, and the experiment was repeated three times, and a drug-free control group was also set. After culturing for 24h, 48h, and 72h, add 20μL of MTT solution to each well, and continue to culture for 4h. Add 130μL ...

Embodiment 2

[0027] Example 2 Experiment of the inhibitory rate of the pharmaceutical composition on the proliferation of HepG2 cells.

[0028] HeG2 cells in logarithmic phase were divided into 1×10 4 The density per well was inoculated in a 96-well plate, 50 μL / well, and drugs were added after 24 hours of culture (50 μL of silibinin, sorafenib, combined group or control solution was added to each well). Among them, the concentrations of silybin were 0.01, 0.05, 0.1, 0.2, 0.4, 0.8 and 1.0 (units are μmol / L), and the concentrations of sorafenib were 0.01, 0.1, 0.2, 0.4, 0.8, 1.6 and 2.0 (units are μmol / L), the concentration of the combination group is (0.01 μmol / L silybin + 0.01 μmol / L sorafenib), (0.05 μmol / L silybin + 0.1 μmol / L sorafenib) fenib), (0.1 μmol / L silybin + 0.2 μmol / L sorafenib), (0.2 μmol / L silybin + 0.4 μmol / L sorafenib), (0.4 μmol / L water Silybin + 0.8μmol / L sorafenib), (0.8μmol / L silybin + 1.6μmol / L sorafenib) and (1.0μmol / L silybin + 2.0μmol / L sora Fini), and each conc...

Embodiment 3

[0034] Example 3 In vitro inhibition experiments of individual drugs and combined drugs on various tumor cells.

[0035] The MTT method was used to determine the concentration of silybin (1 μmol / L), sorafenib (2 μmol / L) alone and the combination of both (0.5 μmol / L silybin + 1 μmol / L sorafenib) within 72 hours. Inhibitory effect on the proliferation of various liver cancer cells (MHCC97, KMHC and HepG2 cells) and renal cancer cells (786-0 cells). The test results are shown in Table 2. Compared with the single drug, the combined drug (0.5 μmol / L silybin + 1 μmol / L sorafenib) has better effects on various malignant tumor cells, especially for those with HepG2 cells, which are closer to primary liver cancer cells, have a better inhibitory effect.

[0036] Table 2 Sorafenib, silybin and the inhibitory effect of the combination of the two on cancer proliferation (measurement time 72 hours)

[0037]

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Abstract

The invention discloses a silibinin and sorafenib-containing pharmaceutical composition, wherein the mass ratio of silibinin to sorafenib in the pharmaceutical composition is (1:1)-(1:5). The pharmaceutical composition can effectively improve the dissolvability of the silibinin and the adverse effect of the sorafenib while the tumor suppression effect is enhanced, and the drug combination of the silibinin and the sorafenib shows better synergism action.

Description

technical field [0001] The invention relates to the field of medicines, in particular to a pharmaceutical composition containing silybin and sorafenib and an application thereof. Background technique [0002] Primary liver cancer (Hepatocellular carcinoma, HCC) is one of the most life-threatening cancers. Although the drugs for the treatment of HCC have made great progress in recent years, due to environmental factors, changes in living habits and the relative lag of the health care system, it has become an important killer affecting human health, and the morbidity and mortality are still rising year by year . At present, there are about 600,000 new patients with liver cancer every year in the world, and more than half (55%) of them come from my country. Therefore, it is imminent to develop new and efficient anti-liver cancer drugs or preparations. [0003] Silybin (silybin) is a flavonoid natural product drug, which is usually used clinically as a hepatoprotective drug t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/44A61P35/00A61K31/357
Inventor 朱峰邓廷丽武俊明
Owner ZHONGXING PHARM CO LTD JIANGSU
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