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Application of salvianolic acid C in preparation of drugs for prevention and treatment of hyperuricemia

A technology of hyperuricemia and salvianolic acid, which is applied in the field of medicine and can solve the problems that have not been reported yet.

Active Publication Date: 2012-04-25
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The salvianolic acid C of the present invention is a non-purine xanthine oxidase inhibitor discovered during a large number of screening studies, and its prevention and treatment of hyperuricemia and gout has not yet been reported.

Method used

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  • Application of salvianolic acid C in preparation of drugs for prevention and treatment of hyperuricemia
  • Application of salvianolic acid C in preparation of drugs for prevention and treatment of hyperuricemia
  • Application of salvianolic acid C in preparation of drugs for prevention and treatment of hyperuricemia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Preparation and structure identification of salvianolic acid C:

[0016] Take 10 kg of Danshen medicinal material, decoct it with water, filter the extract, concentrate under reduced pressure to obtain extract, dissolve the extract in water, adjust the pH value to be acidic, and use macroporous adsorption resin to purify to obtain total phenolic acid and total phenolic acid. The acid was purified by Sephadex LH-20 column and ODS column to obtain compound salvianolic acid C.

[0017] According to HRESI-MS, the molecular formula is C 26 h 20 o 10 ([M-H] - m / z 491.0994, calculated: 491.0984). 1 H-NMR (300MHz, CDCl 3 )δppm: 6.73 (1H, d, J=8.25Hz, H-5), 7.36 (1H, d, J=8.25Hz, H-6), 7.92 (1H, d, J=16.0Hz, H-7) , 6.46(1H, d, J=16.0Hz, H-8), 6.72(1H, d, J=8.0Hz, H-5″), 6.66(1H, d, J=8.0Hz, 1.9Hz, H- 6″), 6.80 (1H, d, J=1.9Hz, H-2″), 3.14 (1H, dd, J=14.4Hz, 4.3Hz, H-7α″’), 3.06 (1H, dd, J= 14.4Hz, 8.2Hz, H-7β″’), 5.25 (1H, dd, J=8.2Hz, 4.3Hz, H-8″), 7.40 (1H, d, J=2.0Hz,...

Embodiment 2

[0020] Xanthine oxidase inhibitory activity of salvianolic acid C

[0021] The xanthine oxidase inhibitory activity of salvianolic acid C was determined by the uric acid production method. The specific experimental method is as follows: fix the concentration of xanthine oxidase (Sigma company, batch number 119K3793) to 0.2 units, add different concentrations of salvianolic acid C (5 μmol / L, 12.5 μmol / L, 25 μmol / L, 50 μmol / L, 75 μmol / L, 100 μmol / L), after incubating at 25°C for 3 minutes, add xanthine 120 μmol / L, measure the UV absorbance at 295 nm, and calculate the inhibition rate. The result is as figure 1 , whose IC 50 =9.07μmol / L, the IC of the positive control drug allopurinol 50 =2.55μmol / L, indicating that salvianolic acid C has strong xanthine oxidase inhibitory activity. Calculate the kinetic constant of salvianolic acid C inhibiting xanthine oxidase according to Lineweaver-Burk's plotting method. The concentration of xanthine oxidase was 0.24units, and the reac...

Embodiment 3

[0023]Direct interaction between salvianolic acid C and xanthine oxidase

[0024] According to the target protein affinity-two-dimensional turbulent flow chromatography-LC / MS online analysis method [Jian-Liang Zhou, Jing-Jing An, Ping Li, Hui-Jun Li, Yan Jiang, Jie-Fei Cheng.Two-dimensional turbulent flow Chromatography coupled on-line to liquid chromatography-mass spectrometry for solution-based ligand screening against multiple proteins.Journal of Chromatography A, 2009, 1216: 2394-2403], the identification of salvianolic acid C and xanthine oxidase (XO) can be directly interaction. Salvianolic acid C with a concentration of 20 μmol / L and xanthine oxidase were incubated at 25°C in the dark for 1 hour, and 20 μL of sample was injected for two-dimensional eddy current chromatography-MSD analysis and detection. At the same time, 20 μL of phosphate buffer (PB) and 20 μmol / L of Salvianolic acid C was used as a control. The result is as image 3 , showing that only salvianolic ...

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Abstract

The present invention relates to the technical field of medicine, specifically to an application of salvianolic acid C in preparation of drugs for prevention and treatment of hyperuricemia. The results of the pharmacological test show that: the salvianolic acid C can be adopted as a xanthine oxidase (XO) inhibitor to prevent and treat hyperuricemia and complications of the hyperuricemia, wherein the complications caused by the hyperuricemia comprise: gout, gouty arthritis, gouty nephropathy, lithangiuria, cardiovascular diseases and other diseases.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of salvianolic acid C in the preparation of medicines for preventing and treating hyperuricemia. Background technique [0002] Xanthine oxidase is widely distributed in the cytoplasm of human heart, lung, liver and other tissues, and can catalyze the oxidation of xanthine and hypoxanthine to generate uric acid and produce peroxide free radicals. The metabolism of purine substances in the human body is disturbed, the synthesis of uric acid is increased or the excretion is decreased, and uric acid is deposited in the joints, cartilage and kidneys in the form of sodium salt, causing an inflammatory reaction of foreign bodies in tissues, that is, gout. It is generally considered that hyperuricemia is a sign of gout, and according to statistics, about 5% to 12% of patients with hyperuricemia eventually develop gout. Hyperuricemia is the most important biochemical bas...

Claims

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Application Information

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IPC IPC(8): A61K31/343A61P19/06A61P19/02A61P13/04A61P13/12A61P9/00
Inventor 陈君李萍高雯
Owner CHINA PHARM UNIV
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