Application of fingolimod hydrochloride to preparation of medicine for treating systemic lupus erythematosus encephalopathy

A technology of fingolimod hydrochloride and lupus erythematosus, which is applied in the field of medicine, can solve the problems that the treatment of lupus encephalopathy has not yet been reported, and achieve the effects of convenient administration, integrity protection, and improvement of behavioral symptoms

Inactive Publication Date: 2017-06-20
THE SECOND AFFILIATED HOSPITAL OF NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In recent years, it has also been reported that FTY720 has curative effect in the treatment of lupus nephritis in B6.MRL-Fas(lpr) / J mice, but its treatment of lupus encephalopathy has not been reported

Method used

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  • Application of fingolimod hydrochloride to preparation of medicine for treating systemic lupus erythematosus encephalopathy
  • Application of fingolimod hydrochloride to preparation of medicine for treating systemic lupus erythematosus encephalopathy
  • Application of fingolimod hydrochloride to preparation of medicine for treating systemic lupus erythematosus encephalopathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] FTY720 treatment improves the behavior of B6.MRL-Fas(lpr) / J mice

[0017] 1. Method: The source of the drug needed for the experiment: FTY720 was purchased from Cayman Chemical Company. The mouse behavior experiment used open field experiment, tail suspension experiment and feeding experiment. C57BL / 6 female mice and B6.MRL-Fas(lpr) / J female mice aged about 8 weeks were divided into 3 groups: C57BL / 6 group, B6.MRL-Fas(lpr) / J group, B6 .MRL-Fas(lpr) / J+FTY720 group. The administration method of the B6.MRL-Fas(lpr) / J+FTY720 group is as follows: B6.MRL-Fas(lpr) / J mice were given 1mg / kg / day FTY720 by intragastric administration from the age of 8 weeks, three times a week , the other two groups were replaced with normal saline, and the feeding experiment, drinking water experiment, tail suspension experiment and open field experiment were carried out at about 20 weeks, and the experimental results were analyzed by SPSS statistical software.

[0018] 2. Results: see figure ...

Embodiment 2

[0033] Effects of FTY720 on Neuronal Apoptosis in Brain Tissue of B6.MRL-Fas(lpr) / J Mice

[0034] 1. Method: Sources of medicines required for the experiment: Neuron apoptosis kit Fluoro-Jade B was purchased from ATT Bioquest. The mice were grouped as described in Example 1, and at 20 weeks, they were sacrificed to obtain brain tissue, stained for neuronal apoptosis, and observed under a fluorescent microscope (see procedure description).

[0035] 2. Results: see figure 2 , After FTY720 treatment, although the number of apoptotic neurons in the hippocampus of the mouse brain tissue decreased, there was no significant difference compared with the untreated group, while the apoptotic number of neurons in the amygdala area decreased significantly compared with the untreated group .

[0036] 3. Step description: Fluoro-Jade B staining

[0037] a. Mice were anesthetized at the age of 20 weeks, and their limbs were fixed on a flat plate. The chest cavity was opened to expose the...

Embodiment 3

[0046] Effects of FTY720 on inflammatory factors in the brain tissue of B6.MRL-Fas(lpr) / J mice

[0047] 1. Method: The source of kits required in the experiment: TNF-α and IL-6 ELISA kits were purchased from BD Company in the United States. The mice were grouped as described in Example 1, and the brain tissues were taken for inflammatory reactions at 20 weeks. factor detection. Anesthetize the mouse and fix it on a flat plate, open the chest cavity, expose the heart, perfuse the ventricle with PBS until the tissue turns white, take the mouse brain tissue, add 500 μL PBS, centrifuge at 12,000 rpm for 5 minutes after homogenization, and take the supernatant for ELISA experiment .

[0048] 2. Results: see image 3 , B6.MRL-Fas(lpr) / J mice have an inflammatory state in the brain tissue, and the levels of TNF-α and IL-6 in the brain tissue are significantly higher than those in C57BL / 6 mice, while the levels of TNF-α and IL-6 in the brain tissue after FTY720 treatment The levels...

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Abstract

The invention provides application of fingolimod hydrochloride to preparation of a medicine for treating systemic lupus erythematosus encephalopathy. The fingolimod hydrochloride (FTY720) can be used for remarkably improving behavioral symptoms of B6.MRL-Fas(lpr) / J mice, reducing the quantity of neuronal apoptosis in brain tissues, alleviating an expression level of brain tissue inflammatory factors, reducing the infiltration of inflammatory cells in brains and protecting the integrity of a blood brain barrier. The FTY720 can be orally taken and the curative effect is remarkable; compared with a traditional intrathecal injection treatment manner, a drug administration manner is more convenient and surgical risks do not exist.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to the application of fingolimod hydrochloride in the preparation of medicines for treating systemic lupus erythematosus encephalopathy. Background technique [0002] Systemic lupus erythematosus encephalopathy (neuropsychiatric syndromes of systemic lupus erythematosus, NP-SLE) is the most serious complication of SLE, with a high mortality rate, and is one of the leading causes of death in lupus crisis. The treatment of NP-SLE includes the treatment of primary disease and symptomatic treatment. The treatment of the primary disease generally adopts intrathecal injection of dexamethasone and methotrexate. Although this treatment method can effectively relieve symptoms and control the condition of encephalopathy, the administration method is not convenient enough, and as a traumatic treatment means, there is a certain surgical risk, and preventive medication cannot be used. The...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/137A61P25/00A61P37/02A61P19/04
CPCA61K31/137
Inventor 周洪施冬艳田通关尤强温爽
Owner THE SECOND AFFILIATED HOSPITAL OF NANJING MEDICAL UNIV
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