Application of dihydromyricetin to prepare medicines treating Parkinson's syndrome as active composition

A technology for dihydromyricetin and Parkinson's disease, applied in the field of medicine

Inactive Publication Date: 2014-10-29
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the commercially available COMT enzyme inhibitors (such as tolcapone and entocapone) have a short metabolic half-life, unsatisfactory in vivo activity, and continuous use can easily cause severe liver toxicity [Neurology2004;62:39-46]
However, PD patients need frequent medication, and long-term use of existing drugs can cause severe liver damage

Method used

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  • Application of dihydromyricetin to prepare medicines treating Parkinson's syndrome as active composition
  • Application of dihydromyricetin to prepare medicines treating Parkinson's syndrome as active composition
  • Application of dihydromyricetin to prepare medicines treating Parkinson's syndrome as active composition

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Using the L-dopa methylation reaction as a probe reaction, with the help of human liver cell plasma in vitro incubation system, dihydromyricetin and plant extracts containing dihydromyricetin (total flavonoids of vine tea, containing 48% dihydromyricetin ) IC for COMT enzyme inhibition 50 , the specific experimental procedure is as follows:

[0016] (1) Add 5mM MgCl to 200 microliters of in vitro metabolic reaction system 2 , 2mM dithiothreitol, 150μM substrate L-dopa, human liver cell plasma protein concentration is 1mg / ml, inhibitor final concentration range is 0.05μM-50μM, pre-incubated at 37℃ for 3 minutes;

[0017] (2) Add S-adenosylmethionine (final concentration: 0.2mM) to the reaction system to initiate the reaction; after reacting at 37°C for 30 minutes, add 200 μl of acetonitrile, shake vigorously, and terminate the reaction;

[0018] (3) Using a high-speed refrigerated centrifuge, under the condition of 20,000×g, centrifuge the above system for 20 minutes a...

Embodiment 2

[0021] Select Kunming mice (purchased from Experimental Animal Center of Dalian Medical University), half male and half male, weighing 18-21 g. The mice were divided into random groups, 20 in each group, half male and half male, and oral acute toxicity tests of dihydromyricetin and total flavonoids of rattan tea were carried out in mice respectively. Dihydromyricetin and vine tea total flavonoids extract were suspended in 0.5% CMC-Na. The experimental groups included different doses of dihydromyricetin (0.1-2g / kg); different doses of total flavonoids of rattan tea (0.1-2g / kg) and 0.5% CMC-Na group. Calculation of LD50 found that the LD50 value of dihydromyricetin and the total flavonoid extract of vine tea containing dihydromyricetin (containing 76% dihydromyricetin) to mice was greater than 2.0g / kg, which belonged to the non-toxic level. In addition, in the human liver microsome incubation system with the addition of the cofactor NADPH or its production system, dihydromyrice...

Embodiment 3

[0023] Select 18 Wistar rats, half male and half female, weighing 180-220g, and randomly divided into 3 groups (oral L-dopa / carbidopa control group, rattan tea total flavonoids / L-dopa / carbidopa group, two Hydromyricetin / L-dopa / carbidopa group), 6 rats / group to carry out the overall pharmacokinetic study of L-dopa. Among them, the total flavonoids of vine tea contain 76% of dihydromyricetin, the dosage is 2g / kg, and the oral dosage of dihydromyricetin is 2g / kg. About 0.5ml of rat plasma samples were collected before administration and at 5, 10, 15, 30, 60, 120, 180, and 240 minutes after administration, and placed in pre-heparinized 1.5ml pointed-bottomed brown centrifuge tubes , after centrifugation at 4000×g for 10 minutes, separate the plasma, add an equal volume of methanol to precipitate protein and centrifuge at a high speed (20,000×g), take the supernatant and store it in a -80°C refrigerator for testing. UFLC-MS / MS was used to measure the blood concentration of L-dopa ...

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Abstract

The invention provides a dihydromyricetin-containing plant extract and application thereof as a superactive catechol methylation transferase inhibitor. The dihydromyricetin-containing plant extract is applicable as a synergist of a medicine levodopa treating Parkinson's syndrome. In-vitro activity determination shows that IC50 of the plant extract inhibiting catechol methylation transferase can reach the micro-mole to nano-mole grade. Rat integral pharmacokinetic research shows that combined usage of dihydromyricetin and levodopa containing the dihydromyricetin-containing plant extract can substantially improve the plasma concentration of levodopa. Additionally, dihydromyricetin and the dihydromyricetin-containing plant extract are high in safety, do not generate active intermediates through metabolism activation, do not combine with a biomacromolecule to form a toxic adduct, and therefore dihydromyricetin and the dihydromyricetin-containing plant extract do not cause liver and kidney toxicity, and are expected to have good application prospect in auxiliary treatment of Parkinson's syndrome.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a dihydromyricetin monomer and a plant extract containing dihydromyricetin. The active ingredient dihydromyricetin can be used as a powerful catechol methyltransferase inhibitor to enhance L- The drug effect of dopa is then used as a Parkinson's disease treatment drug. Background technique [0002] Parkinson's disease (PD) is a chronic degenerative disorder of the central nervous system caused by insufficient dopamine in the brain, and its incidence rate in the elderly is as high as 1.7% [Neurology.2000;54:S24-7]. my country is the country with the largest number of PD patients in the world. With the advent of my country's aging society, the medical, family, and social problems brought about by PD have become more extensive and severe. The PD treatment drug levodopa needs to be used in combination with catechol methyltransferase (COMT) inhibitors before it can exert ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61K36/87A61P25/16A61K31/198
Inventor 杨凌孙晓宇葛广波夏杨柳洪沫宁静邹超
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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