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Application of ginsenoside used as heparanase inhibitor in preparation of tumor therapeutic drug

A technology of heparanase and ginsenoside, which is applied in the direction of antineoplastic drugs, drug combinations, and pharmaceutical formulations, and can solve the complex production process of antibodies and vaccine antagonists, the difficulty of preparing monomer anticoagulant effects, and the production cost advanced questions

Inactive Publication Date: 2017-05-31
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Antibody and vaccine-like antagonists have complex production processes, high production costs, and often cause severe immune reactions
Existing inhibitors such as heparin analogs and sulfated polysaccharides are difficult to prepare monomeric and often have anticoagulant effects

Method used

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  • Application of ginsenoside used as heparanase inhibitor in preparation of tumor therapeutic drug
  • Application of ginsenoside used as heparanase inhibitor in preparation of tumor therapeutic drug
  • Application of ginsenoside used as heparanase inhibitor in preparation of tumor therapeutic drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1 Safety Evaluation

[0039] The research results of the non-clinical safety evaluation of the present invention are as follows:

[0040] 1. Oral acute toxicity test in mice

[0041] Under the conditions of the maximum dosage concentration and maximum dosage volume, the mice were orally given ginsenoside Rk1 12g / kgwt., observed continuously for 14 days, and no death or abnormal toxic reaction was found in the animals. It shows that the maximum tolerated dose of ginsenoside Rk1 mice is 12g / kg wt.

[0042] 2. Beagle dog oral acute toxicity test

[0043] Under the conditions of maximum dosage concentration and maximum dosage volume, Beagle dogs were given ginsenoside Rk12g / kgwt. orally by gavage, and were observed continuously for 14 days. No death or abnormal toxic reaction was found in the animals. It shows that the maximum tolerated dose of ginsenoside Rk1Beagle dog gavage is 2g / kg wt.

[0044] 3. Long-term toxicity of intragastric administration in rats

...

Embodiment 2

[0052] Embodiment 2 Pharmacodynamics

[0053] Research result of the present invention is as follows:

[0054] 1. Ginsenoside Rk1 down-regulates the content of mature heparanase

[0055] Materials: human lung cancer cell A549, heparanase-specific antibody (Santa Cruz), ginsenoside Rk1 (Dalian Meilun Biotechnology Co., Ltd., purity >99%), denaturing polyacrylamide gel electrophoresis system (BioRad).

[0056] method:

[0057] Culture human lung cancer cells A549 to the logarithmic growth phase at 2.0×10 6 Cells / plate were subcultured in 100mm cell culture plate, 37°C, 5% CO 2 Cultivate in the environment for 24 hours, add ginsenoside Rk1 ethanol solution to the medium until the final concentrations of ginsenoside Rk1 are 1, 2, 3, 4, 5 μg / mL (the stock solution is 1 mg / mL ginsenoside Rk1 ethanol solution), 37 °C, 5% CO 2 Continue to culture in the environment for 4 hours, collect the cells, and perform denatured polyacrylamide gel electrophoresis——Western blot detection, th...

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Abstract

The invention relates to application of ginsenoside in the field of pharmacy, in particular to application of ginsenoside used as a heparanase inhibitor in preparation of tumor therapeutic drug. Through tests, the compound has high safety and good inhibition effect on heparanase under the test dosage, and can be used for treating tumors.

Description

technical field [0001] The invention relates to the use of chemical substances in the field of medicine. More specifically, it is the application of ginsenoside as a heparanase inhibitor, and also relates to the application of ginsenoside in the preparation of tumor treatment drugs. [0002] technical background [0003] Heparanase (HPSE-1) is a mammalian β-glucuronidase, the only endonuclease found so far that can cut heparan acetyl sulfate (HS), heparanase from Cleavage of the HS chain at specific sites yields fragments of approximately 5-7 kD. Heparanase promotes cell migration and invasion by cleaving the HS chain on heparan sulfate proteoglycan (HSPG). Heparanase is highly expressed in tumor cells such as lung cancer, esophageal cancer, colorectal cancer, and pancreatic cancer and promotes the invasion and metastasis of tumor cells. At the same time, HPSE can also release angiogenesis-promoting factors such as VEGF, bFGF, and HGF bound on the HS chain to the vicinity ...

Claims

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Application Information

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IPC IPC(8): A61K31/704A61K31/575A61P35/00
CPCA61K31/704A61K31/575
Inventor 金英花林英嘉王宇石李杨王德宇
Owner JILIN UNIV
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