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Application of lariciresinol to preparing medicament for resisting autoimmune disease and graft rejection disease

A technology for larch resin and autoimmune diseases, which is applied in metabolic diseases, skin diseases, bone diseases, etc., can solve the problems of cell non-specificity, high price, and increase the economic burden of patients, and achieve inhibition of occurrence and development, rich sources, The effect of saving treatment costs

Inactive Publication Date: 2011-03-30
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

[0002] Existing immunosuppressants mainly contain cyclosporine A (CsA), corticosteroids, rapamycin, etc. Most of them have obvious adverse reactions, such as nephrotoxicity and non-specificity to cells, etc., and the price is high, increasing Patient financial burden

Method used

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  • Application of lariciresinol to preparing medicament for resisting autoimmune disease and graft rejection disease
  • Application of lariciresinol to preparing medicament for resisting autoimmune disease and graft rejection disease
  • Application of lariciresinol to preparing medicament for resisting autoimmune disease and graft rejection disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The preparation of embodiment 1 larch resin alcohol

[0037] Grind 50Kg of the dried bark of Daphne velvet, reflux extract with 400L of 80% ethanol for 3 times, each time for 3 hours, combine the extracts, concentrate the extracts under reduced pressure to form a liquid extract, add 50L of water to dilute, and then extract with ethyl acetate. 50 L each time, a total of 3 times to obtain 1600 g of ethyl acetate. Apply silica gel column chromatography to the above-mentioned ethyl acetate part, and use the petroleum ether / ethyl acetate system gradient elution with a volume ratio of 100:0 to 1:1, and detect by thin layer chromatography, collect the fraction containing larch resin alcohol, Then, through Sephadex gel chromatography and eluting with chloroform / methanol with a volume ratio of 1:1, 2.15 g of pure larchoresinol compound was obtained.

Embodiment 2

[0038] Example 2 In vitro culture of human dendritic cells and treatment of DCs with agaricol

[0039] Take 50ml / person of peripheral blood from healthy adults intravenously, anticoagulate with heparin, separate peripheral blood mononuclear cells by density gradient centrifugation, suspend cells in RPMI1640 (1640 medium) containing 10% calf serum, and adjust the cell concentration to 2× 10 6 / ml, add to 24-well culture plate, 0.5ml / well, incubate at 37°C, 5% CO2 for 2 hours, make the mononuclear cells adhere to the wall, wash the culture plate lightly with warm serum-free RPMI1640 to remove the adherence cells, that is, to obtain adherent monocytes. Add serum-containing RPMI 1640 containing rhGM-SCF (human recombinant granulocyte colony-stimulating factor) 1000IU / ml and rhIL-4 (human recombinant interleukin 4) 800IU / ml to the culture plate, at 37°C, 5% CO2 After culturing in an incubator for 5 days, add larch resin alcohol with a final concentration of 4 μmol / L for 24 hours,...

Embodiment 3

[0041] Example 3 Effect of larchoresinol on secretion of IL-10 by human dendritic cells

[0042] The dendritic cells of the agarisol-stimulated group and the non-stimulated group were cultured according to the method in Example 1, the supernatant was collected, and the IL-10 content was detected with an IL-10 ELISA (enzyme-linked immunosorbent assay) kit. The concentration of IL-10 secreted by mononuclear cells transformed dendritic cells in vitro in the agarisol stimulation group and the unstimulated group was 2000 ± 22pg / ml, 1200 ± 14pg / ml, and there was a significant difference (Pfigure 1 ).

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Abstract

The invention provides application of lariciresinol to preparing a medicament for resisting an autoimmune disease and a graft rejection disease. An experiment discovers that: the lariciresinol can inhibit human dendritic cell proliferation in vitro and inhibit the capability of human dendritic cells of promoting allogeneic T cell proliferation reaction and enhancing the secretion of interleukin 10. Meanwhile, in an experimental autoimmune myelomeningitis model, the lariciresinol is applied in vivo, so that an average clinical score of mice can be reduced and the spinal infiltration of mononuclear cells is inhibited. In a heart transplant experiment, the lariciresinol is applied in vivo, so that the survival time of a transplanted heart is prolonged. In a delayed hypersensitivity model, the lariciresinol is applied in vivo, so that the auricle swelling degree of the mice can be reduced. In-vivo and in-vitro results both show that: the lariciresinol has the certain effect of resisting the autoimmune disease and graft rejection disease. The medicament is a preparation which consists of the lariciresinol serving as an active ingredient and a medical carrier, and comprises an oral preparation, an injection, a suppository, an external preparation and the like.

Description

technical field [0001] The present invention relates to medicines. It specifically relates to the preparation of drugs with new indications, especially the application of agarisol in the preparation of drugs against autoimmune diseases and transplant rejection diseases. Background technique [0002] Existing immunosuppressants mainly contain cyclosporine A (CsA), corticosteroids, rapamycin, etc. Most of them have obvious adverse reactions, such as nephrotoxicity and non-specificity to cells, etc., and the price is high, increasing patient financial burden. How to use traditional Chinese medicine and its active ingredients to prevent and treat autoimmune diseases and transplant rejection is one of the important directions of modernization research of traditional Chinese medicine. [0003] Dendritic cells (DC) are currently the most powerful antigen-presenting cells known in the body, which can effectively activate the proliferation and differentiation of initial T cells, re...

Claims

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Application Information

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IPC IPC(8): A61K31/341A61P37/00A61P37/06A61P5/16A61P3/10A61P1/16A61P1/04A61P11/00A61P13/12A61P25/00A61P27/02A61P9/00A61P21/04A61P19/02A61P29/00A61P17/00A61P37/08A61P11/06
Inventor 于益芝张卫东苏娟曹雪涛单磊戴先坤李江燕张寿德
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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