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Tripterygium wilfordii composition for inhibiting drug-resistant cancer as well as preparation method and application of tripterygium wilfordii composition

A composition, the technology of Tripterygium wilfordii, applied in the field of biomedicine, can solve the problems of liver damage, high pharmacological toxicity, skin pigmentation, etc., and achieve the effects of reduced toxicity, simple and easy operation of separation steps, and high repeatability

Active Publication Date: 2022-07-29
HUAQIAO UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Although, in recent years, the overall chemical composition of Tripterygium wilfordii, especially the evaluation of the toxic effects of triptolides, has attracted increasing attention from scholars at home and abroad, but because there are many components in the original plant, root, bark and leaves of Tripterygium wilfordii, many of the ingredients are in the original plant. The content is extremely low, such as triptolide is only 0.012% (120mg / kg), which limits the application research of a single tripterygium compound
At present, more than 380 biologically active chemical components have been isolated and identified from Tripterygium wilfordii. Some active molecules can inhibit tumors, such as triptolide, but their pharmacological toxicity is very high. For example, oral administration can stimulate the gastric mucosa, causing nausea, Symptoms such as vomiting, abdominal pain, and diarrhea can also cause liver damage, skin pigmentation, rashes, and oral ulcers, resulting in decreased white blood cells

Method used

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  • Tripterygium wilfordii composition for inhibiting drug-resistant cancer as well as preparation method and application of tripterygium wilfordii composition
  • Tripterygium wilfordii composition for inhibiting drug-resistant cancer as well as preparation method and application of tripterygium wilfordii composition
  • Tripterygium wilfordii composition for inhibiting drug-resistant cancer as well as preparation method and application of tripterygium wilfordii composition

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0036] The present invention provides a preparation method of the Tripterygium wilfordii composition. Compound combinations. .

[0037] In the present invention, the specific preparation method for the analysis sample of the Tripterygium wilfordii suspension cell extract is: after drying the Tripterygium wilfordii suspension cells, perform Soxhlet reflux extraction with 20 mL of ethyl acetate, extract 3 times, combine the extracts, Using a rotary evaporator, the solvent was recovered, the residue was evaporated to dryness and dissolved in 1 ml of methanol, 500 ul of methanol solution and 3 g of silica gel powder were mixed, and the sample was loaded. The amount of silica gel filler was 20 g. Rinse with 200mL petroleum ether eluent first, and discard the eluent. Then use 200mL of different ratios of petroleum ether:ethyl acetate eluent (9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9, 0:10) for elution, and 10 fractions were collected. Use a rotary evaporator to recover the sol...

Embodiment 1

[0050] The combined inhibitory effect of the compound of Example 1 on cisplatin-resistant cells A549 / DDP

[0051] 1. Cell model establishment

[0052] Non-small cell lung cancer cells A549 and H1299, human large cell lung cancer cells H460 cisplatin-resistant cells, namely A549 / DDP and H1299 / DDP and H460 / DDP, and normal human lung bronchial epithelial cells 16HBE were used as cultured cells. Cultured in PRMI-1640 complete medium at 37°C, CO 2 The concentration of 5%, cultured to a certain number, can establish three cell models.

[0053] 2. Determination of the inhibition rate of the compound on cell proliferation

[0054] Take the three kinds of cells in the logarithmic growth phase obtained in step 1, respectively, to 5 × 10 4 The density of cells / mL was seeded in 96-well plates. 90 μL of cells were added to each well, and complete medium was set as blank control group, DMSO negative control, TP positive control and experimental groups added with different concentrations...

Embodiment 2

[0073] Example 2 Combined inhibitory effect of five compounds on cisplatin-resistant cells H1229 / DDP

[0074] The experimental design, five compounds, and the method for measuring the inhibitory effect on cisplatin-resistant cells H1229 / DDP are the same as those in Example 1.

[0075] from Figure 5 It can be seen that compared with the control group, the five compounds have significant inhibitory activity on H1299 / DDP cells, among which the inhibitory activity of compound P is stronger than that of TP, and its IC 50 It was found to be 12.80μg / ml. It was found that the proliferation inhibition effect of the two drugs was significantly improved. Compared with the single drug group, the cell inhibition rate was increased by 2.08, 3.24, 3.19, 2.36, and 2.06 times, showing a significant difference. The synergistic effect of TP combination therapy.

[0076] For H1299 / DDP cells, see Table 4 and Image 6 As shown, when the TP concentration dose is 2.5 μg / ml, the combined drug inde...

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Abstract

The invention provides a tripterygium wilfordii composition for inhibiting drug-resistant cancers, and the composition is prepared from triptolide, 1 beta-E-cinnamoyloxy-4a-hydroxy-5a, 7 beta, 11-triacetoxy-8 beta-nicotinoyloxy-dihydroagarofuran, demethylzeylasteral, TriptobeneneR, (3S, 4S, 5R, 10S)-3, 19-dihydroxy-7-oxidized abietane-8, 11, 11-triacetoxy-8beta-nicotinoyloxy-dihydroagarofuran, 1 beta-E-cinnamoyloxy-4a-hydroxy-5a, 7 beta, 11-triacetoxy-8 beta-nicotinoyloxy-dihydroagarofuran, 1 beta-E-cinnamoyloxy-4a, 7 beta, 11-triacetoxy-8 beta-nicotinoyloxy- The composition is composed of any one or two of 1, 3, 4, 5, 6, 7, 13-triene and TriptobenzeneB. The invention further discloses a preparation method of the composition. The composition disclosed by the invention has the advantages that the toxicity is lower than that of triptolide, and the drug effect of inhibiting the proliferation of tumor drug-resistant cells is enhanced, and compared with single triptolide, the composition disclosed by the invention has the effects of reducing toxicity and enhancing efficacy.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a tripterygium wilfordii composition for inhibiting drug-resistant cancer and a preparation method and application thereof. Background technique [0002] Tripterygium wilfordii is a deciduous creeping shrub of the family Euonymus genus Tripterygium wilfordii, aliased as Zhenlonggen, steamed dragon grass, mangcao, yellow vine grass, heartbroken grass, mountain arsenic, etc., with roots, leaves, flowers and fruits as medicine, mainly produced in In Zhejiang, Anhui, Jiangxi, Hunan, Guangdong, Guangxi, Fujian, Taiwan, Yunnan and other places, its active ingredients are very complex, and its pharmacological effects mainly include immune regulation, anti-tumor, improvement of microcirculation, anti-inflammatory, bactericidal, antipyretic and analgesic etc.; clinically it can be used to treat leprosy reaction, rheumatoid arthritis, tuberculosis and other chronic diseases...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/585A61K31/56A61K31/443A61K31/122A61K31/05A61K36/37A61P35/00A61P35/02
CPCA61K31/585A61K31/56A61K31/443A61K31/122A61K31/05A61K36/37A61P35/00A61P35/02A61K2300/00Y02A50/30A61K31/365A61K31/192A61K31/352A61K31/341
Inventor 张景红欧阳静茹何秀枝杨素心
Owner HUAQIAO UNIVERSITY