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Applications of human carboxylesterase inhibitor using extract product or monomer components of Psoralea corylifolia

A technology of psoraleae extract and carboxylesterase, applied in the field of medicine, can solve the problems of not alleviating delayed-type diarrhea, reducing drug dosage, affecting bioavailability and the like, achieving good therapeutic effect, high inhibitory activity and convenient taking Effect

Inactive Publication Date: 2016-01-27
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 inhibitory effect of psoralen and its chemical components on human carboxylesterase has not been reported, nor has there been any report on the use of psoralen and its chemical components to relieve delayed diarrhea caused by CPT-11
In addition, many oral drugs containing carboxylate bonds are often metabolized by carboxylesterases distributed in the gastrointestinal tract, and are easily hydrolyzed into water-soluble active drugs before being absorbed into the blood, thereby reducing their absorption into the blood. The amount of drug that affects bioavailability

Method used

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  • Applications of human carboxylesterase inhibitor using extract product or monomer components of Psoralea corylifolia
  • Applications of human carboxylesterase inhibitor using extract product or monomer components of Psoralea corylifolia
  • Applications of human carboxylesterase inhibitor using extract product or monomer components of Psoralea corylifolia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Determination of Inhibitory Activity of Psoraleae Extract on Human Carboxylesterase Subtypes

[0030] Using the hydrolysis metabolism of fluorescein diacetate as a probe reaction, with the help of human liver microsome in vitro incubation system, the enzyme activity was rapidly evaluated by 96-well plate fluorescence method to screen medicinal materials with inhibitory activity against human carboxylesterase (hCE2) . The specific experimental process is as follows:

[0031] (1) In 200 microliters of in vitro metabolic reaction system, containing phosphate buffer solution with pH 7.4, the concentration of human liver microsomal protein is 2 μg / ml, psoralen is extracted with 95% ethanol for 3 hours after grinding, and the concentration is 0.3 g / ml, take 2ul of each extract and shake and pre-incubate at 37°C for 10 minutes;

[0032] (2) Add the substrate (final concentration: 10 μM) to the reaction system to initiate the reaction; after reacting at 37° C. for 30 minutes,...

Embodiment 2

[0036] Identification of main components of psoraleae extract inhibiting carboxylesterase

[0037] With the help of high-performance liquid chromatography, the extract components of the traditional Chinese medicine psoraleae were separated, and the separated liquid was collected every 30 seconds, and added to the in vitro incubation system of human liver microsomes to achieve the hydrolysis and metabolism of fluorescein diacetate. For the probe reaction, the inhibitory activity of the above fingerprints on carboxylesterase was measured at each access time period, and the psoralen components with inhibitory activity were identified by mass spectrometry.

[0038] (1) The traditional Chinese medicine Psoraleae was extracted by ultrasonication in 95% ethanol (0.3g / ml) for 3 hours, centrifuged in a high-speed refrigerated centrifuge at 20,000×g and 4°C for 20 minutes, and the supernatant was taken.

[0039] (2) The chromatographic conditions adopted are: ODS chromatographic column ...

Embodiment 3

[0048] Quantitative evaluation of the inhibitory ability of psoralen chemical constituent monomers to carboxylesterase

[0049] Using the hydrolytic metabolism of fluorescein diacetate as a probe reaction, the IC of carboxylesterase inhibition by different psoraleae extracts was determined by means of human liver microsome in vitro incubation system 50 , the specific experimental process is as described in Example 2:

[0050] Table 2 The inhibitory ability IC of psoralen chemical composition monomers to carboxylesterase 2 50

[0051]

[0052]

[0053] a. In 200 microliters of in vitro metabolic reaction system, containing phosphate buffer at pH 7.4, the concentration of human liver microsomal protein is 2 μg / ml, and the final concentration of inhibitors is in the range of 1 μM-80 μM, pre-incubated with shaking at 37°C for 10 minute;

[0054] b. Add the substrate (final concentration 10 μM) to the reaction system to initiate the reaction; after reacting at 37°C for 30 ...

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Abstract

The invention provides applications of a human carboxylesterase inhibitor using an extract product or monomer components of Psoralea corylifolia, and the applications belong to the field of medicine technology. The human carboxylesterase inhibitor using the extract product or monomer components of Psoralea corylifolia is used for alleviating delayed-onset diarrhea caused by a plurality of clinic chemotherapeutics or improving bioavailability of ester medicaments and prolonging metabolic half-life of the medicaments. The extract product of Psoralea corylifolia is a 25%-95% ethanol extract; main monomer chemical components of the extract product of Psoralea corylifolia comprise: neobavaisoflavone, corylifolinin, corylifolin A, bavachinin A, bakuchiol, bavachin or isobavachin. In vitro activity determination shows the IC50 value of the extract product of Psoralea corylifolia or monomer components for inhibiting carboxyle sterase is 0.8-6.4 micromole, the safety of the compounds is good, which prompts the fact that the compounds have good application prospects.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the application of a psoraleae extract or its monomer component as a human carboxylesterase inhibitor. Background technique [0002] Carboxylesterases (CEs) belong to group B esterases, and the CEs involved in the metabolism of ester drugs in the human body are mainly carboxylesterase 1 (hCE-1) and carboxylesterase 2 (hCE-2). hCE-1 is highly expressed in the liver, and exists in macrophages, lung epithelial cells, heart, testis and other tissues, but little expression in the gastrointestinal tract. hCE-2 is present in small intestine, colon, kidney, liver, heart and brain tissue. CEs participate in the hydrolysis and metabolism of various endogenous and exogenous compounds in the body, and cooperate with other metabolic enzymes or carriers to play an important role in the metabolism and clearance of ester drugs. CEs can hydrolyze a variety of drugs or ester prodrug...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K36/487A61K31/37A61K31/352A61K31/05A61K31/12A61K31/4745A61P1/12A61P35/00
Inventor 杨凌李耀光葛广波李世阳刘兆明吕侠
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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