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Antineoplastic pharmaceutical composition and application thereof

A technology of anti-tumor drugs and compositions, applied in the field of medicine, to achieve the effects of convenient operation, reduced toxicity, and reduced damage

Inactive Publication Date: 2018-02-09
TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] So far, there is no report on the combined use of cetuximab and oridonin in antitumor therapy and the synergistic effect of the two in antitumor

Method used

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  • Antineoplastic pharmaceutical composition and application thereof
  • Antineoplastic pharmaceutical composition and application thereof
  • Antineoplastic pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1: the preparation method of oridonin

[0039] Dried the aboveground part (9kg) of Rubescens japonicus, refluxed and extracted with 10 times the amount of 95% ethanol solution for 3 times, each time for 2 hours, and recovered the obtained ethanol extract until it had no alcohol smell to obtain the extract. The extract was dissolved in water, degreased with an equal volume of petroleum ether, and then extracted with an equal volume of ethyl acetate to obtain 180 g of ethyl acetate layer extract. Afterwards, the ethyl acetate layer extract was separated by silica gel column chromatography, and dichloromethane and methanol were used in volumes of 100:0, 100:1, 100:2, 100:3, 100:5, 100:7, and 100:10. By continuous elution, the crude product of oridonin was obtained, and white needle crystals (3g) were obtained by recrystallization.

[0040] The white needle crystals (MeOH) were positive for the reaction of vanillin-concentrated sulfuric acid. Combined with 1H a...

Embodiment 2

[0047] Example 2: Molecular docking

[0048] 1 Experimental method

[0049] Molecular docking of Rubescensin A and EGFR was carried out using Autodock4.23 molecular docking software, and the binding free energy of Rubescensin A and EGFR was obtained.

[0050] 2 Experimental results

[0051] Depend on figure 1 It can be seen that Rubescensin A binds to Lys721 and Asp831 of EGFR in the form of hydrogen bonds, and binds to Val702, Leu694 and Leu820 in the form of hydrophobic bonds. The binding free energy of oridonin A to EGFR is -8.34kcal / mol, and its binding site is the intracellular ATP binding site of EGFR (Cell, 2006, 125:1137-1149). Normally, the binding free energy predicted by Autodock reaches -9kcal / mol, which means that the affinity can reach the nM level. The molecular docking research results combined with the previous experimental research results suggest that Rubescensin A has a strong binding ability to EGFR.

Embodiment 3

[0052] Example 3: The growth inhibitory effect of cetuximab combined with oridonin on human laryngeal squamous cell carcinoma HEp-2 cells and Tu212 cells

[0053] 1 Experimental method

[0054] (1) MTT assay for cell proliferation: HEp-2 and Tu212 cells were inoculated in RPMI-1640 medium containing 10% fetal bovine serum, 1×105 U / L penicillin and 100 g / L streptomycin, in a 5% CO2 incubator , cultured at 37°C. HEp-2 and Tu212 cells in the logarithmic growth phase were seeded in 96-well plates at 3×104 and 5×104 cells per well, respectively. After culturing for 24 hours, cetuximab at concentrations of 0, 1, 10, and 100 μg / mL and 0, 12, 24, and 36 μM oridonin were added. Three replicate wells were set up for each group, and a negative control was set up at the same time. Place in a 5% CO2 incubator at 37°C for 24 and 48 hours. Add 100 μL of 5 mg / mL MTT to each well, and after culturing for 2.5 hours, carefully discard the culture medium in the well, add 150 μL of DMSO to eac...

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Abstract

The invention provides a pharmaceutical composition and an application thereof, wherein the pharmaceutical composition consists of oridonin and cetuximab. The pharmaceutical composition, when used fortreating laryngeal cancer, shows an obvious synergistic effect. Based upon both in-vivo and in-vitro experiments, it is proved that the pharmaceutical composition provided by the invention can obviously inhibit the growth of laryngeal cancer cells, and the pharmaceutical composition is subjected to a mechanism of inhibiting the activation of an EGFR signaling pathway; and meanwhile, the pharmaceutical composition can promote the generation of reactive oxygen so as to induce apoptosis of the laryngeal cancer cells and cell cycle arrest. The pharmaceutical composition provided by the invention,when used for treating the laryngeal cancer, has the advantages of being obvious in antineoplastic effect and low in toxic and side effects.

Description

technical field [0001] The invention relates to an anti-tumor pharmaceutical composition and its application, in particular to a composition of cetuximab and oridonin and its application for anti-laryngocarcinoma, belonging to the technical field of medicine. Background technique [0002] Head and neck cancer is the sixth most common cancer worldwide. Among them, laryngeal cancer (laryngeal cancer) is a common malignant tumor in the head and neck. In my country, the disease accounts for about 1% to 5% of systemic tumors. There are 1.5 to 3.4 new cases of laryngeal cancer among 100,000 cancer patients in my country every year. The pathological classification of laryngeal carcinoma is mainly squamous cell carcinoma. In recent years, with the aggravation of industrial pollution, the incidence of laryngeal cancer has a clear upward trend (Cancer Treatment Reviews, 2006, 32: 504-515; Clinical Otolaryngology & Allied Sciences, 2001, 26: 442-446). Due to the inconspicuous symptom...

Claims

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Application Information

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IPC IPC(8): A61K39/395C07D493/10A61P35/00A61K31/352
CPCA61K39/3955A61K31/352A61K2039/505C07D493/10A61K2300/00
Inventor 康宁曹世杰邱峰高秀梅张强
Owner TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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