Application of p-hydroxyl acetophenone glycosidase to medicine for autoimmunity disease and transplant rejection disease

A para-hydroxyacetophenone, autoimmune disease technology, applied in metabolic diseases, skin diseases, bone diseases and other directions, can solve the problems of increasing the economic burden of patients, non-specific cells, adverse reactions, etc., to reduce the economic burden of patients, inhibit Occurrence and development, rich sources of effects

Inactive Publication Date: 2015-03-11
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of these drugs have obvious adverse reactions, such as nephrotoxicity and non-specificity to cells, etc., and the price is high, which increases the economic burden of patients, thus limiting their clinical application

Method used

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  • Application of p-hydroxyl acetophenone glycosidase to medicine for autoimmunity disease and transplant rejection disease
  • Application of p-hydroxyl acetophenone glycosidase to medicine for autoimmunity disease and transplant rejection disease
  • Application of p-hydroxyl acetophenone glycosidase to medicine for autoimmunity disease and transplant rejection disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1: Preparation of p-hydroxyacetophenone glucoside

[0037]Rabbit wind (Incarvillea delavay) whole herb 30kg, reflux extraction with 80% ethanol 2L each time for 3 times, each time for 2 hours, combined extracts, concentrated under reduced pressure to obtain 600g extract, diluted with 3L of water, adjusted with 2% HCl pH to 2-3, filter to obtain filtrate and filter residue, add 20% NaOH to the filtrate to adjust pH to 11, extract with chloroform three times, 2 L each time, to obtain chloroform fraction; concentrate the chloroform extraction fraction under reduced pressure to obtain 250 g of crude product. Mix the crude product with 500g of silica gel (200-300 mesh) to mix the sample, elute with chloroform-acetone (20:1-2:1) system gradient, and collect p-hydroxyacetophenone glucoside (detected by thin-layer chromatography) Fractions were subjected to C18 reverse-phase silica gel (40-70 μm) column chromatography, gradient elution with methanol-water (50%-80%), ...

Embodiment 2

[0038] Example 2 In vitro culture of human dendritic cells and treatment of DCs with p-hydroxyacetophenone glucoside

[0039] 50 mL / person of peripheral blood from healthy adults was extracted intravenously, anticoagulated with 1% sterile heparin, and density gradient centrifugation was used (2000r / min for 20min, carefully absorb the white cloudy mononuclear cells in the interface layer, and 2000r / min was used in a 15mL centrifuge tube) Centrifuge once, centrifuge once at 1500r / min, centrifuge once at 1000r / min, separate the peripheral blood mononuclear cells, suspend the cells with RPMI1640 (1640 medium) containing 10% calf serum, adjust the cell concentration to 2×10 6 / mL, add to 24-well culture plate, 0.5mL / well, 37℃, 5%CO 2 The incubator was cultured for 2 hours to make the monocytes adhere to the wall, and the culture plate was lightly washed with warm serum-free RPMI1640 to remove the adherent cells, so as to obtain the adherent monocytes. Add serum-containing RPMI1640...

Embodiment 3

[0041] Example 3 Effect of p-Hydroxyacetophenone Glucoside on Human Dendritic Cells Secreting IL-10

[0042] Dendritic cells of p-hydroxyacetophenone glucoside treatment group and untreated group cultured according to the method of Example 2, supernatants were collected, and IL-10 was detected with an ELISA (enzyme-linked immunosorbent assay) kit for IL-10. 10 content. The concentration of IL-10 secreted by monocyte-transformed dendritic cells in the p-hydroxyacetophenone glucoside treatment group and the untreated group was 435±22pg / mL and 92±14pg / mL, and there was a significant difference (Pfigure 1 ).

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Abstract

The present invention provides application of p-hydroxyl acetophenone glycosidase to medicine for autoimmunity disease and transplant rejection disease. Through experiments, p-hydroxyl acetophenone glycosidase is found to be capable of restraining multiplication of human dendritic cells in vitro, restraining human denderitic cells to promote breeder reaction of allogeneic T cells, and enhancing the ability of human denderitic cells to secrete interleukin 10. In a model of experimental autoimmunity disease cerebrospinal meningitis, p-hydroxyl acetophenone glycosidase is capable of reducing an average mouse clinical score and restraining spinal cord invasion degree of the mononuclear cells. In an experiment of heart transplantation, p-hydroxyl acetophenone glycosidase is capable of prolonging the survival time of the transplanted heart. In a model of delayed type hypersensitivity, p-hydroxyl acetophenone glycosidase is capable of reducing mouse ear swelling degree. According to the results both in vivo and in vitro, p-hydroxyl acetophenone glycosidase possesses a certain effect on autoimmunity disease and transplant rejection disease. The medicine provided by the invention comprises p-hydroxyl acetophenone glycosidase as an active component and a medicinal carrier, and the medicine includes oral dosage form, injection, suppository, and topical dosage form, etc.

Description

technical field [0001] The present invention relates to medicines. It specifically relates to the new application of medicines, especially the application of p-hydroxyacetophenone glucoside in the preparation of medicines against autoimmune diseases and transplantation rejection diseases. Background technique [0002] Existing immunosuppressants mainly include cyclosporine A (CsA), corticosteroids, and rapamycin. However, most of these drugs have obvious adverse reactions, such as nephrotoxicity and non-specificity to cells, etc., and the price is high, which increases the economic burden of patients, thus limiting their clinical application. [0003] p-Hydroxyacetophenone glucoside is an active ingredient alkaloid extracted from the traditional Chinese medicine Incarvillea delavay, which has been found to have antibacterial, anti-inflammatory, hemostatic, antiviral, liver protection and anti-tumor properties And so on. [0004] Dendritic cells (DCs) are currently known t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/7034A61P37/06A61P37/02A61P3/10A61P1/16A61P1/00A61P25/00A61P19/02A61P21/04A61P13/12A61P11/06A61P37/08A61P5/16A61P17/00
Inventor 张卫东于益芝岳荣彩曹雪涛单磊苏娟
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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