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Triptolide and application of modifier thereof to inhibition of antibody generation by B cells

A technology of triptolide and B cells, applied in the medical field, can solve the problems of poor prognosis, poor treatment effect, and poor prognosis of patients

Inactive Publication Date: 2017-06-27
THE THIRD AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Rejection after transplantation is the main reason affecting the survival time of grafts. Rejection is divided into cell-mediated rejection and antibody-mediated rejection (AMR). Compared with T-cell-mediated cellular rejection, B cells participate in The treatment effect of acute or chronic AMR after transplantation is poor, and the prognosis of patients is poor. It belongs to refractory rejection. Therefore, how to inhibit the production of antibodies by B cells has always been an urgent problem in the field of transplantation immunity.
Acute AMR after organ transplantation (kidney transplantation, skin transplantation, lung transplantation, etc.) is mainly caused by circulating antibodies (DSA), the treatment effect is poor, the prognosis is poor, and it is a refractory acute rejection reaction
[0003] Triptolide is a monomer extracted from the traditional Chinese medicine Tripterygium wilfordii. It has been found to have four major functions: anti-tumor, anti-reproductive, anti-inflammatory and immunosuppressive. Its immunosuppressive effect has long been reported and has been used in clinical Chinese patent medicines. : It can treat rheumatism, arthritis, skin diseases, immune-related nephritis, etc., but the effect of triptolide on the production of antibodies to B cells has not been reported

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  • Triptolide and application of modifier thereof to inhibition of antibody generation by B cells

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Embodiment 1

[0024] Embodiment 1 in vivo experiment

[0025] Experimental method: The experiment was divided into two groups, the experimental group and the control group, both underwent C3h→Balb / c skin transplantation (H2k→H2d), 6 rats in each group. The experimental group used the modified triptolide, i.e. dimethylamine acetyltriptolide citrate for injection (Product No. MC002), which was metabolized into triptolide in mice to play a role in the receptor Balb / c Mice were injected subcutaneously at a dose of 1 mg / Kg, and the frequency was once every other day; the control group was injected with the same amount of normal saline, with the same frequency. Blood samples were taken from the two groups of mice at 2, 4, 6, 8, 12, 16, 24, and 28 days after skin transplantation, and the DSA intensity in the samples was detected and compared between the groups. The results are as follows: figure 1 shown.

[0026] The DSA detection method is as follows: take the whole spleen of the donor, grind a...

Embodiment 2

[0028] Embodiment 2 in vitro experiments

[0029] The applicant of the present invention considers the current effect of triptolide on B cells. At present, there is no in vitro experimental research for reference, so the concentration exploration is carried out in the pre-experiment stage, and the concentration of triptolide used in other cells is referred to. And under the premise of not affecting the activity of B cells, explore the effect of triptolide at the concentration range of 0.04ng / ml-4μg / ml on the apoptosis of B cells, using different concentrations (0.04ng / ml-4μg / ml) of triptolide Purified peripheral blood CD19 treated with phallidine (TPL) and control group dimethyl sulfoxide (DMSO) + cells, i.e. B cells for 8 days, and detected PI by flow cytometry + (propidium iodide) concentration, used to detect the number of apoptotic cells. The result is as figure 2 As shown, when triptolide is at a concentration of 4ng / ml, it has no effect on the apoptosis of B cells, a...

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Abstract

The invention discloses triptolide and application of a modifier thereof to inhibition of antibody generation by B cells. The inventor utilizes triptolide to treat mice sensitized caused by skin grafting of different strains, it is found that triptolide can inhibit generation of a circulating antibody DSA, and an in vitro experiment is further adopted to verify that triptolide can inhibit antibody generation by the B cells. The invention discloses a new application of triptolide. It is verified that triptolide and the modifier thereof can inhibit antibody generation by the B cells, and the basis can be provided for preparing medicines for inhibit antibody generation by the B cells.

Description

technical field [0001] The invention relates to the use of triptolide and its modification in immunosuppression, in particular to the application of triptolide and its modification in inhibiting B cells from producing antibodies, and belongs to the medical field. Background technique [0002] Rejection after transplantation is the main reason affecting the survival time of grafts. Rejection is divided into cell-mediated rejection and antibody-mediated rejection (AMR). Compared with T-cell-mediated cellular rejection, B cells participate in Acute or chronic AMR after transplantation has poor treatment effect and poor prognosis, which belongs to refractory rejection. Therefore, how to inhibit the production of antibodies by B cells has always been an urgent problem in the field of transplantation immunity. Acute AMR after organ transplantation (kidney transplantation, skin transplantation, lung transplantation, etc.) is mainly caused by circulating antibody (DSA), with poor tr...

Claims

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Application Information

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IPC IPC(8): A61K31/585A61P37/06
CPCA61K31/585
Inventor 孙启全
Owner THE THIRD AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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