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Applications of dihydroquercetin in preparing medicines for protecting drug-induced acute liver injury

A technology of drug-induced liver injury and dihydroquercetin, which is applied in the directions of drug combination, pharmaceutical formula, organic active ingredients, etc., can solve problems such as liver injury that have not yet been seen

Inactive Publication Date: 2018-10-16
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there is no research report on its use to protect acetaminophen-induced liver injury

Method used

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  • Applications of dihydroquercetin in preparing medicines for protecting drug-induced acute liver injury
  • Applications of dihydroquercetin in preparing medicines for protecting drug-induced acute liver injury
  • Applications of dihydroquercetin in preparing medicines for protecting drug-induced acute liver injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Example 1. Dihydroquercetin protects primary hepatocyte injury induced by acetaminophen

[0015] Primary mouse hepatocytes were obtained from C57BL / 6 mice, extracted by IV collagenase in situ perfusion, and seeded in 96-well plates, divided into blank control group and model control group (APAP 10 mM) , dihydroquercetin treatment group (12.5, 25, 50, 100, 200 μM) and positive drug (NAC 2.5 mM) treatment group, after cultured at 37 ℃ for 24 hours, MTT detection was carried out, and the cell proliferation rate was calculated. The results showed that, with Dihydroquercetin significantly attenuated acetaminophen-induced growth inhibition of primary hepatocytes with increasing doses (e.g. figure 1 shown).

Embodiment 2

[0016] Example 2. Dihydroquercetin attenuates acetaminophen-induced release of lactate dehydrogenase in primary hepatocytes

[0017] Primary hepatocytes were seeded in 96-well plates and cultured overnight. Dihydroquercetin (12.5, 25, 50, 100, 200 μM) and positive drug (NAC 2.5 mM) were pretreated in advance, and acetaminophen was added 1 hour later (10 mM) treatment, cultured at 37°C for 24 hours, then detected lactate dehydrogenase (LDH) and calculated the release rate of LDH. The results showed that, with the dose increasing, dihydroquercetin significantly reduced the paracetamol-induced primary Hepatocyte LDH release (eg figure 2 shown).

Embodiment 3

[0018] Example 3. Dihydroquercetin regulates the abnormality of biochemical indicators of liver function in mice induced by acetaminophen

[0019] C57BL / 6 mice were fasted for 12 hours before the experiment, and 25 mg / kg, 50 mg / kg and 100 mg / kg of dihydroquercetin (dissolved in 25% β-cyclodextrin) were injected intraperitoneally with NAC 600 mg / kg was used as a positive control, 500 mg / kg of acetaminophen was injected intraperitoneally 1 hour later, sacrificed 24 hours later, and whole blood and liver tissues were collected. The results of ALT and AST tests showed that dihydroquercetin could significantly reduce paraacetyl The abnormal increase of ALT and AST in mouse serum induced by aminophenol (such as image 3 shown).

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Abstract

The invention belongs to the field of pharmacy, relates to applications of dihydroquercetin in preparing medicines for protecting drug-induced acute liver injury, and in particular relates to applications of dihydroquercetin in preparing medicines for protecting drug-induced liver injury induced by acetaminophen. The cell and animal experiments prove that dihydroquercetin can weaken primary hepatocyte growth inhibition and death induced by acetaminophen, and can improve the abnormal increase of the liver-function-relevant biochemical index and the change of the pathologic structure of the C57BL / 6 mice induced by acetaminophen. Dihydroquercetin can be used for preparing medicines used for treating drug-induced liver injury, especially the treatment medicines for acute liver injury induced by acetaminophen.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to the use of dihydroquercetin in the preparation of drugs for protecting drug-induced acute liver injury, especially the use of dihydroquercetin in the preparation of drugs for protecting drug-induced liver injury induced by acetaminophen use. Background technique [0002] The prior art discloses that drug-induced liver damage (Drug-induced liver damage, DILD) is an inevitable problem in drug development and clinical application, among which acetaminophen (Acetaminophen, APAP)-induced liver damage is the most common and can be Severe hepatic necrosis, liver failure and even death. At present, the commonly used treatment method in clinical practice is to use the method of intravenous infusion to remove the oxidant N-acetylcysteine ​​(NAC). Studies have shown that NAC, as a precursor of glutathione, can reduce the oxidative stress in the liver. Its disadvantages It has a short half-life, is o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61P1/16
CPCA61K31/352
Inventor 刘洪瑞鞠佃文宰文静
Owner FUDAN UNIV