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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: 2022-07-29
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
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Effect test

Embodiment 1

[0027] After the mice were anesthetized, each mouse was injected with 200 μl of emulsion containing Mog35-55 peptide antigen and complete Freund's adjuvant (CFA), followed by injection of 250 ng of pertussis toxin (PTX), and 48 h later A second injection of 250ng pertussis toxin. On the 10th to 12th day after modeling, the mice began to show weakness of the tail, and the paralysis of the hind limbs occurred on the 18th day at the peak of the onset. Administered immediately after the secondary immunization of mice for 48 hours, a mouse EAE model for the prevention of MS (Multiple sclerosis) was obtained (see figure 1 ), the prevention group models were divided into the following groups: modeling group (immune modeling only, 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); after the 18th day after the secondary...

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 48h later, the first test was performed. A second injection of 250ng pertussis toxin. On day 18 after immunization, mice were EAE modeled (EAE disease score reached 3). Mice were intraperitoneally injected with GA 5 mg / kg.bw and 10 mg / kg.bw or administered by gavage with 10 mg / kg.bw of Teflon for 18 consecutive days. On day 36, mice were sacrificed. Both GA and teflunomide reduced the average EAE disease score to 2.3, see ( figure 2 in a). In addition, luxol fast blue staining and MBP immunostaining showed that GA treatment improved white matter pathology ( figure 2 in c). Transmission microscopy revealed new thin myelin sheaths around spinal cord axons in the GA-treated group. In GA-treated mice, g values ​​were significantly lower (P figure 2 in the...

Embodiment 3

[0032] In a mouse model of EAE, reactive immune cells that enter the integrated central nervous system (CNS) reactivate autoreactive CD4+ T cells by self-antigen-presenting APCs and recruit monocytes to the CNS, resulting in more Severe MS inflammation. Th1 and Th17 cells are the predominant CD4+ T cell subsets associated with MS, which are detected in the early stages of multiple sclerosis in the CNS. To determine whether GA inhibits Th1 or Th17 cells, this example examined the ratio of Th1 and Th17 cells relative to CD4+ T cells in the central nervous system of EAE mice, CD4+IL-17+ in the CNS of GA-treated mice T cell and CD4+IFN-γ+ T cell infiltration were significantly less than in GSH-treated MOG35-55 immunized mice, and Th17 cells were more easily inhibited by GA than Th1 cells ( image 3 in a). Enzyme-linked immunospot assay (ELISPOT) analysis of CNS-derived monocytes confirmed the above results, with GA treatment leading to a decrease in pro-inflammatory cytokines (I...

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Abstract

The invention provides an application of a gold complex in preparing a medicine for preventing and / or treating multiple sclerosis, and belongs to the technical field of biomedicine. Gold complexes have good biosafety and can inhibit the activity of pro-inflammatory cytokine receptor-related tyrosine kinase JAK1 in immune cells, regulate the differentiation of naive CD4+ T cells to Th17 cells, and inhibit the expression of inflammatory factors level to achieve prevention and treatment of multiple sclerosis. The gold complex molecule can prevent or treat the occurrence of EAE in mice, and the preventive effect is as high as 2 / 3, showing a significant effect of treating EAE in mice. Gold complex molecules can enter the immune cells of the central nervous system of EAE mice through in vivo metabolism, and inhibit the differentiation of naive CD4+ T cells to Th17 cells and the secretion of IL-17 inflammatory factors by inhibiting the activity of JAK1 cells. But it does not affect the activity of immune cells.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and particularly relates to the application of gold complexes in the preparation of medicines for preventing and / or treating multiple sclerosis. Background technique [0002] Multiple Sclerosis (MS) is one of the most prevalent neurological disorders in the world, causing non-traumatic disability in young adults. Currently, drugs used to improve multiple sclerosis inhibit immune cell activation, reduce the infiltration of activated immune cells, and destroy neuronal myelin 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 flu-like symptoms and increased rates of malignancy. SUMMARY OF THE INVENTION [0003] The purpose of the present invention is to provide the application of gold complexes in the preparation of medicines for preventing...

Claims

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Application Information

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Patent Type & Authority Patents(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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