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Application of neuraminidase and inhibitor in preparing medicine for treating pulmonary fibrosis and renal fibrosis

A technology of neuraminidase and pulmonary fibrosis, applied in the field of biomedicine, can solve the problems of undiscovered neuraminidase correlation

Active Publication Date: 2018-04-20
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In subsequent studies, the applicant also found that neuraminidase is related to various diseases. After searching, no prior art has been found to disclose the relationship between neuraminidase and these diseases

Method used

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  • Application of neuraminidase and inhibitor in preparing medicine for treating pulmonary fibrosis and renal fibrosis
  • Application of neuraminidase and inhibitor in preparing medicine for treating pulmonary fibrosis and renal fibrosis
  • Application of neuraminidase and inhibitor in preparing medicine for treating pulmonary fibrosis and renal fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Example 1: Relationship between neuraminidase and its inhibitors and pulmonary fibrosis

[0020] 1. Experimental method

[0021] Grouping and administration: SPF male C57BL / 6 mice (weight 20-24g) were adaptively reared for 3-5 days and then randomly divided into sham operation group (control group), model group, zanamivir, oseltami phosphate Wei, coptisine, salvianolic acid B administration group. Except for the control group, which was injected with equal volume of sterile saline, the other groups were injected with BLM (5 mg / kg) through the trachea to establish models. After 2 hours, the mice in the administration group were given 0.2 mg / kg / d zanamivir (i.v.), 5 mg / kg / d oseltamivir phosphate (p.o.), 40 mg / kg / d coptisine (p.o.), 40 mg / kg / d salvianolic acid B (p.o.), the model group and the control group were given an equal volume of vehicle 0.5% CMC-Na by gavage for 4 weeks. 2 hours after the last administration, the patients were sacrificed by exsanguination of the...

Embodiment 2

[0031] Example 2: Relationship between neuraminidase and its inhibitors and renal fibrosis

[0032] 1. Experimental method

[0033] Grouping and administration: Male clean-grade Wistar rats (body weight 160-180 g) were adaptively reared for 3-5 days and then randomly divided into sham operation group (control group), model group and zanamivir, oseltamivir phosphate, Coptis alkaloid, salvianolic acid B administration group. Except for the control group, the other groups of rats were modeled. The modeling method is as follows: after the rats were anesthetized by ip 10% chloral hydrate (4ml / kg), the rats were fixed in the right lateral position on the operating table, the skin was routinely prepared for disinfection, the left abdominal incision was made, and the rats were separated layer by layer. The tissue was extended to the peritoneum, the left ureter was exposed and freed, and the upper 1 / 3 and the middle 1 / 3 of the ureter were ligated with silk threads, and then the urete...

Embodiment 3

[0043] A commercially available neuraminidase inhibitor screening kit P0309 (Beyotime, Beyotime) was used to test the inhibitory activity of salvianolic acid B in vitro, and the positive control drug was oseltamivir phosphate. Add 70 μL of buffer and 10 μL of neuraminidase solution to each well of the 96-well plate, then add 10 μL of different concentrations of the solution to be tested, shake and mix, incubate at 37°C for 5 min, add 10 μL of the solution containing the fluorescent substrate, and shake to mix. After 30min incubation at 37°C, fluorescence measurement was performed, where the excitation wavelength was 322 nm and the emission wavelength was 450 nm. According to the fluorescence readings, the inhibition rates of different test solutions were calculated, and the IC50 values ​​of the positive control drugs oseltamivir phosphate and salvianolic acid B were further obtained. The results are shown in Table 3.

[0044] Table 3 IC50 values ​​of positive control drugs os...

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Abstract

The invention discloses application of neuraminidase and an inhibitor in preparing a medicine for treating pulmonary fibrosis and renal fibrosis. Reports show that zanamivir and oseltamivir phosphateare effective inhibitors of neuraminidase, the inhibition functions of coptisine to neuraminidase are also already disclosed in former patents of the inventor, and the inventor also finds that danshinolic acid B is capable of inhibiting activity of neuraminidase in vitro and is a neuraminidase inhibitor; tests show that the neuraminidase inhibitors are capable of effectively inhibiting activity ofneuraminidase in lung and kidney tissue, and furthermore pulmonary fibrosis and renal fibrosis can be inhibited. Therefore, neuraminidase and inhibitors thereof can be adopted to prepare medicines for treating pulmonary fibrosis and renal fibrosis.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to the application of enzymes and enzyme inhibitors, in particular to the application of neuraminidase and the inhibitors in preparing medicines for treating pulmonary fibrosis and renal fibrosis. Background technique [0002] Neuraminidine is a class of natural sugar acid compounds that are widely present in living organisms. Now it is determined that there are more than 50 natural derivatives of neuraminic acid, among which N-acetylneuraminic acid and N-glycolylneuraminic acid are the more common ones. Neuraminidine is usually linked to the end of glycoconjugates such as glycoproteins and glycolipids in the form of short chain residues. Neuraminidine is an important biological information transmission molecule, and the neuraminidation modification of cell surface glycoproteins and glycolipids plays a crucial role in many biological processes, including cell adhesion, antigen recognition, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/47A61K31/4375A61K31/343A61K31/351A61K31/215A61P11/00A61P13/12
CPCA61K31/215A61K31/343A61K31/351A61K31/4375A61K38/47C12Y302/01018
Inventor 张蕾齐炼文魏婷婷
Owner CHINA PHARM UNIV
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