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Application of gold complex in preparation of medicine for preventing and/or treating multiple sclerosis

A multiple sclerosis and gold complex technology, applied in the field of biomedicine, can solve the problems of flu-like symptoms and high incidence of malignant tumors, accompanied by side effects, etc., to achieve the prevention and treatment of multiple sclerosis, good biological Safety, good weight recovery effect

Active Publication Date: 2021-06-22
BEIJING UNIV OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although first-line broad-spectrum immunosuppressive drugs such as Teriflunomide reduce immune cell activity and reduce the frequency of MS relapses, it is often associated with side effects such as increased flu-like symptoms and a high incidence of malignancies

Method used

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  • Application of gold complex in preparation of medicine for preventing and/or treating multiple sclerosis
  • Application of gold complex in preparation of medicine for preventing and/or treating multiple sclerosis
  • Application of gold complex in preparation of medicine for preventing and/or treating multiple sclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] After mice were anesthetized, 200 μl of emulsion containing Mog35-55 peptide antigen and complete Freund's adjuvant (CFA) was injected into the back of each mouse, followed by injection of 250 ng of pertussis toxin (PTX), and the first injection was performed 48 hours later. A second injection of 250 ng of pertussis toxin was given. On the 10th to 12th day after modeling, the mice began to have tail weakness, and the hind limbs were paralyzed on the 18th day at the peak of the onset. Administer immediately after the secondary immunization of mice 48h, obtain the prevention mouse EAE model of MS (Multiple sclerosis, multiple sclerosis) (see figure 1 ), the prevention group model is divided into the following groups: Modeling group (only immune modeling, no therapeutic intervention, vehicle), GA high concentration group (10mg / kg.bw), GA low concentration group (5mg / kg.bw) , the positive drug group (Teriflunomide, 10mg / kg.bw), the ligand control group (GSH, 10mg / kg.bw); a...

Embodiment 2

[0030] After the mice were anesthetized, 200ul of emulsion containing Mog35-55 peptide antigen and complete Freund's adjuvant (CFA) was injected into the back of each mouse, followed by 250ng of pertussis toxin (PTX), and the first A second injection of 250 ng of pertussis toxin was given. On day 18 after immunization, mice were modeled with EAE (EAE disease score reached 3). Intraperitoneal injection of GA5mg / kg.bw and 10mg / kg.bw to mouse EAE or intragastric administration of 10mg / kg.bw of teflunomide for 18 consecutive days. On day 36, mice were sacrificed. Both GA and terflunomide reduced the mean EAE disease score to 2.3, see ( figure 2 in a). Furthermore, luxol fast blue staining and MBP immunostaining showed that GA treatment improved white matter pathology ( figure 2 in c). New thin myelin around the spinal cord axons of the GA-treated group was observed by transmission microscopy. In GA-treated mice, g values ​​were significantly lower (P figure 2 in c. In add...

Embodiment 3

[0032] In a mouse model of EAE, reactive immune cells entering the central nervous system (CNS), reactivated autoreactive CD4+ T cells via self-antigen presentation of APCs, and recruited monocytes to the CNS, resulting in more Severe MS inflammation. Th1 and Th17 cells are the main CD4+ T cell subtypes associated with MS, and they are detected in the early stages of multiple sclerosis in the CNS. In order to determine whether GA can inhibit Th1 or Th17 cells, this example detected the proportion of Th1 and Th17 cells relative to CD4+ T cells in the central nervous system of EAE mice, and the CD4+IL-17+ T cells in the CNS of GA-treated mice T cells and CD4+IFN-γ+ T cell infiltration were significantly less than GSH-treated MOG35-55 immunized mice, and Th17 cells were more susceptible to GA inhibition than Th1 cells ( image 3 in a). ELISPOT analysis of CNS-derived monocytes confirmed the above results, and GA treatment resulted in a decrease in the pro-inflammatory cytokine ...

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Abstract

The invention provides application of a gold complex in preparation of a medicine for preventing and / or treating multiple sclerosis, and belongs to the technical field of biological medicine. The gold complex has good biological safety, and can inhibit the activity of pro-inflammatory cytokine receptor related tyrosine kinase JAK1 in immune cells, regulate the differentiation of young CD4 + T cells to Th17 cells, inhibit the expression level of inflammatory factors, and prevent and treat multiple sclerosis. The gold complex molecule can prevent or treat mouse EAE, the prevention effect is up to 2 / 3, and the obvious mouse EAE treatment effect is shown. Gold complex molecules can enter immune cells of a central nervous system of an EAE mouse through in-vivo metabolism, and by inhibiting the activity of cell JAK1, differentiation of young CD4 + T cells to Th17 cells and secretion of IL-17 inflammatory factors are inhibited, but the activity of the immune cells is not affected.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of gold complexes in the preparation of drugs for preventing and / or treating multiple sclerosis. Background technique [0002] Multiple Sclerosis (MS) is one of the most prevalent neurological diseases in the world, causing non-traumatic disability in young people. Currently, the drugs used to improve multiple sclerosis are to inhibit the activation of immune cells, reduce the infiltration of activated immune cells and destroy neuronal myelinating cells. Although first-line broad-spectrum immunosuppressive drugs such as teriflunomide reduce immune cell activity and reduce the frequency of MS relapses, it is often associated with side effects such as increased flu-like symptoms and a high incidence of malignancies. Contents of the invention [0003] The purpose of the present invention is to provide the application of gold complexes in the prepar...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/242A61K38/02A61P25/00
CPCA61K33/242A61K38/02A61P25/00
Inventor 高学云何哲圣高福平
Owner BEIJING UNIV OF TECH
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