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Application of triptonide to anti-angiogenesis drugs

A technology of triptolide ketone and anti-vascular, applied in the field of medicine, can solve problems such as no experimental evidence, no anti-angiogenesis, etc.

Active Publication Date: 2013-08-07
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0021] (4) The anti-angiogenesis effect of triptolide ketone has not been reported so far: However, according to the existing literature research and scientific and technological search, the effect of triptolide ketone on neovascularization has not been reported in domestic and foreign literature and patents. In 1972, Kupchan et al. discussed the relationship between the chemical structure of triptolide and triptolide and its anti-leukemic activity in a 2-page research communication, and only used one sentence to mention the effect of triptolide on leukemia. The proliferation of cells is inhibited, but the research communication does not produce any experimental evidence
In addition, Zhu Yongliang declared the diterpene lactone compound of Tripterygium wilfordii for the treatment of cancer, but did not involve the anti-angiogenesis effect
In summary, there have been no reports and patents on the anti-tumor angiogenesis effect of triptolide at home and abroad so far.

Method used

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  • Application of triptonide to anti-angiogenesis drugs
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Effect of triptolide on tumor cell adhesion in vitro

[0038] Tumor cell adhesion and migration are necessary steps for tumor angiogenesis and tumor metastasis. The inventors first investigated whether triptolide could inhibit tumor cell adhesion.

[0039] (1) Experimental materials

[0040] Tumor cell line: human lung cancer cell H1299 was frozen in our laboratory; cell culture medium DMEM (high glucose) was a product of Hyclone Company.

[0041]Test drug: triptolide (purchased from a commercial company) was dissolved in dimethyl sulfoxide (DMSO), and diluted with DMEM (high sugar) medium to the desired concentration; gelatin was purchased from Sigma.

[0042] (2) Experimental method

[0043] Human tumor cells were treated with different concentrations of triptolide for 24 hours, resuspended in serum-free medium, counted viable cells with trypan blue, adjusted cell density and seeded in 96-well plates coated with 0.1% gelatin. After the cells adhered to ...

Embodiment 2

[0049] Example 2: Inhibitory effect of triptolide on tumor cell migration in vitro

[0050] The faster the tumor cells migrate, the stronger the metastases. The inventors studied the effect of triptolide on the migration of tumor cells in vitro, and found that triptolide can inhibit the migration of tumor cells.

[0051] (1) Experimental materials

[0052] Tumor cell line: human lung cancer cell H1299 was frozen in our laboratory; cell culture medium DMEM (high glucose) was a product of Hyclone Company.

[0053] Test drug: triptolide (purchased from a commercial company) was solubilised with dimethyl sulfoxide (DMSO), and diluted to the required concentration with DMEM (high glucose) medium.

[0054] (2) Experimental method

[0055] Human lung cancer H1299 cells in the logarithmic growth phase were inoculated in a 6-well plate at a suitable density, scratched after 24 hours, the medium was discarded, washed with PBS three times, and 5% triptolide containing different concent...

Embodiment 3

[0060] Example 3: Inhibitory effect of triptolide on the formation of tumor vessel-like network structure

[0061] As mentioned above, tumor cells play an important role in tumor angiogenesis. The inventors used tumor cells with angiogenesis ability as a model to study the effect of triptolide on the ability of tumor cells to form a blood vessel-like network structure.

[0062] (1) Experimental materials

[0063] Tumor cell lines: Human lung cancer cells H1299, A549 and pancreatic cancer cells PaTu8988 were from ATCC and were cryopreserved in our laboratory; the cell culture medium DMEM (high glucose) was the product of Hyclone Company.

[0064] Test drug: purified triptolide (purchased from a commercial company with a purity greater than 95%) was dissolved in dimethyl sulfoxide (DMSO), diluted to the required concentration with DMEM (high sugar) medium; Matrigel reagent was purchased Rui-Ji's dye was purchased from BD Company and Nanjing Jiancheng Technology Co., Ltd.

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Abstract

The invention relates to the medicine field and discloses application of triptonide to anti-angiogenesis drugs. In-vitro and in-vivo tests for suppressing tumor neovascularization are carried out by adopting triptonide and the results show that the Chinese herbal medicine monomer triptonide can induce silencing of key genes for tumor neovascularization, promote tumor cell aging, differentiation and apoptosis, eliminate or reduce the neovascularization capacities of tumor cells, normalize and eliminate tumor vessels and improve the anticancer curative effects. Effective dose of triptonide and pharmaceutically acceptable auxiliary components can be used for preparing tablets, granules, capsules, suspension agents, syrup, emulsion or other common drug preparations. The drug preparations can be used for anti-angiogenesis. Besides, the extracts containing triptonide can be used for preparing the anti-angiogenesis drug preparations.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of triptolide in antiangiogenesis drugs. Background technique [0002] The global cancer death toll reaches 10 million every year. At present, the cause of death of a quarter of the world's population is caused by cancer. Malignant tumors have become the culprit that seriously endangers human life. Drugs for clinical prevention and treatment of tumors can be roughly divided into two categories: the first category is various chemotherapeutic drugs that directly kill tumors, which are most widely used in clinical practice, but have encountered severe side effects, easy drug resistance, and high treatment costs during development. and many other bottlenecks; the second class of drugs that inhibit tumor angiogenesis and tumor metastasis, such as angiogenesis inhibitors. The growth and metastasis of tumor cells require a complete vascular system, so preventing tumor angiogenes...

Claims

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Application Information

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IPC IPC(8): A61K31/585A61P35/00
Inventor 周泉生曹志飞
Owner SUZHOU UNIV
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