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Application of fexofenadine in preparation of medicine for preventing and treating intervertebral disc degeneration

A technology of fexofenadine and intervertebral disc, applied in the field of medicine, can solve the problem that the effect has not been studied yet.

Pending Publication Date: 2021-09-07
SHANDONG UNIV QILU HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although fexofenadine is widely used in allergic rhinitis and chronic idiopathic urticaria, its role in disc degeneration has not been studied

Method used

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  • Application of fexofenadine in preparation of medicine for preventing and treating intervertebral disc degeneration
  • Application of fexofenadine in preparation of medicine for preventing and treating intervertebral disc degeneration
  • Application of fexofenadine in preparation of medicine for preventing and treating intervertebral disc degeneration

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] This embodiment verifies the efficacy of fexofenadine in preventing TNF-α-induced intervertebral disc degeneration, and the experimental method is as follows:

[0063] (1) In the case of adding or not adding fexofenadine (50uM), the mouse intervertebral disc tissue was cultured and treated with TNF-α (10ng / ml) for 7 days, and stained with Safranin O. The specific operation method is to operate according to the product manual.

[0064] Such as figure 2 As shown in , the Control group is a blank group (safranin O staining is only performed on the mouse intervertebral disc tissue, without adding TNF-α and FFD), and the TNF-α group is used without adding fexofenadine (50uM). TNF-α (10ng / ml) was cultured and treated for 7 days; TNF-α+FFD group was cultured and treated with TNF-α (10ng / ml) for 7 days with fexofenadine (50uM). Depend on figure 2 The stained pathological pictures showed that fexofenadine had a protective effect on TNF-α-induced intervertebral disc degenera...

Embodiment 2

[0074] This embodiment verifies that fexofenadine can inhibit the intervertebral disc degeneration in the tail injury rat model, and the experimental method is as follows:

[0075]A rat model of acupuncture injury was established. The method for establishing the model is as follows: after killing the mice, disinfect the skin surface with 75% alcohol. The area between the 8th and 9th tail vertebrae (Co8-Co9) of rats was punctured with a 20-gauge needle parallel to the tailbone to a depth of 5 mm. Then rotate the needle 360 ​​degrees, in order to eliminate the injection effect, intraperitoneally inject the same volume of PBS or FFD (10mg / kg body weight) every other day

[0076] (2) After culturing and treating the tail injury rat model with or without fexofenadine (concentration 50uM) for 8 weeks, Safranin O staining and HE staining were performed on the rat intervertebral disc. The staining result is as Figure 13 (Safranin O staining) and Figure 14 Shown (HE staining).

...

Embodiment 3

[0082] This example verifies that fexofenadine can inhibit the degradation of extracellular matrix mediated by TNF-α, and the experimental method is as follows:

[0083] (1) Mice nucleus pulposus cells were treated with or without fexofenadine (10 μM) in the presence or absence of TNF-α (10 ng / mL). After 8 hours, the total RNA was extracted, and the mRNA expressions of Aggrecan, Col-II and SOX-9 were detected by PCR technique. The result is as Figure 20 shown. The figure shows that the expressions of Aggrecan, Col-II and SOX-9 in the extracellular matrix were increased in the nucleus pulposus cells of mice treated with FFD (10 μM), indicating that fexofenadine inhibited TNF-α-mediated extracellular Matrix degradation.

[0084] (2) Human nucleus pulposus cells were treated with or without fexofenadine (10 μM) in the presence or absence of TNF-α (10 ng / mL). After 8 hours, the total RNA was extracted, and the mRNA expressions of Aggrecan, Col-II and SOX-9 were detected by PC...

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Abstract

The invention relates to application of fexofenadine in preparation of a medicine for preventing and treating intervertebral disc degeneration. Research finds that fexofenadine can directly enter nucleus pulposus cells to be combined with cPLA2 in the cells after being injected into a body, cPLA2 phosphorylation is inhibited, then NF-kB phosphorylation is influenced, TNF-alpha mediated inflammatory reaction is inhibited, the cell stability is effectively protected, TNF-alpha induced cell apoptosis and inflammatory factor generation are further reduced, and the local inflammatory response is reduced by inhibiting the generation of the inflammatory factors. Besides, fexofenadine can also inhibit the generation of TNF-alpha mediated MMP-13 (cartilage matrix degrading enzyme), so that the destructive effect of the destructive enzyme on intervertebral disc tissues is reduced and prevented, and the integrity of the intervertebral disc tissues is kept. According to the application, the drug indications of fexofenadine are expanded, and a new drug treatment scheme is provided for preventing and treating intervertebral disc degeneration.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to the use of fexofenadine in the preparation of medicines for preventing and treating intervertebral disc degeneration. Background technique [0002] Intervertebral disc degeneration (IDD) is an important pathological factor causing neck, shoulder and back pain, and plays an important role in the major diseases affecting people's health in the world today. IDD has caused a significant economic burden and medical expenses to the society, and brought a heavy burden to the people's medical expenditure and the national medical finance. Intervertebral disc degeneration is a kind of inflammatory degeneration. The main reason is that the increase of TNF-α leads to the aggravation of inflammatory response, triggers the production of downstream inflammatory factors and the increase of expression of destructive matrix enzymes, and destroys the intervertebral disc structure. [0003] Fexo...

Claims

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Application Information

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IPC IPC(8): A61K31/445A61K9/00A61P19/08A61P29/00
CPCA61K31/445A61K9/0019A61P19/08A61P29/00
Inventor 蔚建鲁程雷刘凯文
Owner SHANDONG UNIV QILU HOSPITAL
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