Compound capable of inhibiting mast cell degranulation and preparation method and application thereof

A mast cell and compound technology, applied in the field of medicine, can solve the problem of limited compounds, achieve wide application prospects, and inhibit mast cell degranulation

Inactive Publication Date: 2017-05-10
SHANGHAI UNIV OF T C M
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Mast cell stabilizers prevent mast cells from degranulating or releasing histamine and other components or "mediators" during an allergic reaction. Drugs currently marketed as mast cell stabilizers include disodium cromoglycate, which works by interacting with the outer membrane of sensitive mast cells. Combined with the calcium channel of the compound, prevent calcium influx, inhibit mast cell degranulation, reduce the release of various inflammatory mediators such as histamine, slow reactants, leukotrienes, etc., but the compounds with similar mechanism of action are still very limited. Continued screening is needed for new compounds that may act as mast cell stabilizers

Method used

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  • Compound capable of inhibiting mast cell degranulation and preparation method and application thereof
  • Compound capable of inhibiting mast cell degranulation and preparation method and application thereof
  • Compound capable of inhibiting mast cell degranulation and preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0036] Embodiment 1: the preparation of compound of the present invention

[0037] a) reflux extraction of 17.5kg Magnolia magnolia medicinal material with 95vol% ethanol aqueous solution (extraction three times, each solvent consumption is 60L, extraction 2h), and filter and collect the filtrate;

[0038] b) extract the filtrate with petroleum ether, and separate the liquid and discard the petroleum ether layer, and collect the water layer;

[0039] c) extracting the aqueous layer with ethyl acetate, and separating and discarding the aqueous layer, collecting the ethyl acetate layer;

[0040] d) The ethyl acetate layer was concentrated under reduced pressure, and the ethyl acetate crude extract was chromatographically separated with an MCI column, and the mobile phase was sequentially ethanol: water=1:9, 2:8, 4:6, 5:5, 6 :4, 7:3, 9:1, according to thin-layer chromatography, the flow fraction is divided into eight parts, which are recorded as Fr.E1~E8;

[0041] e) Chromatogr...

Embodiment 2

[0053] Embodiment 2: investigate the impact of compound of the present invention on mast cell degranulation

[0054] Using mast cells (BMMC cells), anti-mouse-DNP-IgE was added overnight, drug intervention was performed for 30 min, and then DNP-BSA was added for 30 min to stimulate degranulation of BMMC cells, and the release of β-hex was detected.

[0055] (1) BMMC cell culture

[0056] Bone marrow was extracted from C57BL / 6 mice, cultured in RPMI 1640 with 30ng / L IL-3 and 10% FBS at 37°C, 5% CO 2 Cultivate in an incubator for four weeks, and after detecting that the mast cell purity is higher than 99%, culture with RPMI1640 of 10 ng / L and 10% FBS, and passage once every 5 days.

[0057] (2) Cell sensitization

[0058] will be 0.5*10 6 Add 0.1 μg / mL anti-mouse-DNP-IgE / mL BMMC cells, at 37°C, 5% CO 2 Incubate overnight in the incubator.

[0059] (3) Dosing intervention

[0060] After 24 hours, 25 μM of the compound of the present invention diluted with HEPES buffer or 5 ...

Embodiment 3

[0074] Embodiment 3: the compound of the present invention is to the influence of mouse passive skin allergy

[0075] Balb / c mice were treated with chlorpheniramine 4mg / kg / d or sample group 50mg / kg / d for 4 days. Inject 0.2 mL of mouse anti-trichosanthin serum into the two auricles of each mouse, continue to administer the drug or solvent for 2 days after injecting the serum, and inject 0.5% Evans blue antigen injection (containing 1.25 mg ovalbumin) 0.25 mL, the animal was sacrificed after 30 min, the two ears were cut off, placed in 0.75 mL of 1 mol / L KOH solution, digested overnight at 37°C, and 3.5 mL of 0.6 mol / L H 3 PO 4 solution and acetone mixture (5:13, volume ratio), centrifuge, take the supernatant, and measure the absorbance with a spectrophotometer (640nm). Data are mean±SE, n=10. ***P<0.0001.

[0076] (1) Breeding of Balb / c mice

[0077] Balb / c mice were kept in the mouse experimental feeding room with barrier system (temperature: 22-23°C, humidity: 50-70%, w...

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Abstract

The invention discloses a compound capable of inhibiting mast cell degranulation and a preparation method and application thereof. The molecular formula of the compound is C22H2606, the molecular weight is 386.17, and the chemical structural formula is shown in the description. As proved by research results, the compound can significantly inhibit the release of beta-hexane in mast cells at the inhibition rate of 85.57 percent, has a significant inhibitory effect on mast cell degranulation, is expected to be used as an active ingredient in the preparation of a medicament for inhibiting mast cell mast cell degranulation, can be further used as an active ingredient in the preparation of a mast cell stabilizer medicament and the preparation of a medicament for preventing or / and treating allergic diseases, has a wide application prospect.

Description

technical field [0001] The invention relates to a compound capable of inhibiting mast cell degranulation, a preparation method and application thereof, and belongs to the technical field of medicine. Background technique [0002] Mast cells are widely distributed around the capillaries and lymphatic vessels in the skin, lymphoid tissue, uterus, bladder, mucous membrane and submucosal connective tissue of the respiratory tract and digestive tract. Mast cell degranulation is one of the causes of many pathological reactions in the body, and it has varying degrees of relationship with tumorigenesis, blood lipid clearance, angiogenesis, nervous system function, sexual cycle changes of the reproductive system, and allergic reactions. Mast cells not only play a key role in allergic reactions, but also show functional polymorphisms in many diseases, such as: inflammatory response, cytotoxicity, growth and formation of blood vessels, and immune regulation. participate. [0003] Mas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D493/04A61K31/34A61P37/08A61P17/00A61P11/06A61P11/02
CPCC07B2200/07C07D493/04
Inventor 李医明张行钱菲毛高慧吴喜民许锦文
Owner SHANGHAI UNIV OF T C M
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