Application of glycerophosphorylcholine in preparation of medicines for preventing and treating tuberculosis

A technology for glycerophosphocholine and tuberculosis, applied in the field of biomedicine, can solve the problems of unreported application, unclear function and mechanism, etc., and achieve the effect of inhibiting deterioration and no cytotoxicity

Active Publication Date: 2021-12-24
SHANGHAI PULMONARY HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] In the early stage, through the comparative metabolomics analysis of the lungs and peripheral blood of Mtb-infected granulomatous mice, we found that the content of glycerophosphocholine (GPC) in the lung granulomas and peripheral blood of mice was significantly down-regulated, suggesting that GPC may be involved in In the occurrence and development of tuberculous granuloma, but its role and mechanism in the progression of granuloma are still unclear, especially the application in the preparation of drugs for the prevention and treatment of tuberculosis has not been reported

Method used

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  • Application of glycerophosphorylcholine in preparation of medicines for preventing and treating tuberculosis
  • Application of glycerophosphorylcholine in preparation of medicines for preventing and treating tuberculosis
  • Application of glycerophosphorylcholine in preparation of medicines for preventing and treating tuberculosis

Examples

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Embodiment 1

[0031] The present embodiment utilizes the C57BL / 6 mouse infection model to analyze the effect of GPC on tuberculosis. The specific experimental process and results are as follows:

[0032] 6-8 week old female C57BL / 6 mice, 6 in each group, were infected with H37Rv strain by intranasal route, about 200 CFU / mouse. After 3 weeks of infection, the control group was supplemented with 1% DMSO in the drinking water, and the GPC group was supplemented with GPC (1%) in the drinking water, and the mice were sacrificed 4 weeks after the administration. The effect of GPC on tuberculosis was analyzed by detecting the following indicators:

[0033] (1) The amount of bacteria in the organs: collect part of the lungs under sterile conditions, add PBS to homogenize, inoculate on 7H10 agar medium after 10-fold dilution, culture at 37°C for 4 weeks, observe the growth of Mtb, and calculate the amount of bacteria in the lungs , it was found that the amount of bacteria in the lungs infected with...

Embodiment 2

[0037] The present embodiment utilizes the zebrafish infection model to analyze the effect of GPC on mycobacterial diseases, especially granulomas. The specific experimental steps and results are as follows:

[0038] Wild-type zebrafish (AB strain) were obtained from China Zebrafish Resource Center, reared in a recirculating aquaculture system, and transferred to a toxicology system for infection experiments. The standard conditions for zebrafish feeding and infection were ensured that the water temperature was about 28°C, and the pH was about 28°C. 7.4, the conductivity is about 1,500 μS. Adult zebrafish were first anesthetized with 0.1% tricaine, and then infected with Mycobacterium marinum by intraperitoneal injection, with a bacterial count of about 200 CFU. One week later, the control group was orally administered DMSO, and the GPC group was orally administered 0.1 mg / Fish GPC. After 1 week of administration, they were killed, and the effect of GPC on the development of g...

Embodiment 3

[0043] In this example, the in vitro infection model of macrophages was used to analyze the effect of GPC on the survival of intracellular Mtb in macrophages. The specific experimental steps and results are as follows:

[0044] Wild-type mouse peritoneal primary macrophages were taken and cultured in complete 1640 medium (containing 10% FBS + 1% penicillin-streptomycin) at 37°C for 4 hours. After the cells adhered, they were replaced with complete 1640-free medium, and GPC was added. The final concentration was 1 mM, and 12 hours later, H37Rv was infected with MOI=2. After 3 hours of infection, the supernatant was removed, the cells were washed twice with PBS to remove extracellular bacteria, and the number of bacteria entering the cells was counted by CFU. After another part of the cells was washed, 1640 medium containing DMSO or 1 mM GPC was added to continue culturing for 24 hours, and the survival of intracellular bacteria was detected by CFU counting. It was found that G...

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Abstract

The invention provides application of glycerophosphorylcholine (GPC) in preparation of medicines for preventing and treating tuberculosis. The invention verifies that the GPC inhibits intracellular survival and in-vivo survival of mycobacterium tuberculosis by enhancing expression of antibacterial peptides in macrophages, inhibits deterioration of tuberculous granuloma, has no cytotoxicity, and can be used as a new effective metabolic molecule for preparing the medicines for preventing and treating the tuberculosis, and a new strategy is provided for treating the multidrug-resistant tuberculosis.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of glycerophosphocholine in the preparation of medicines for preventing and treating tuberculosis. Background technique [0002] Tuberculosis (TB) is a major infectious disease that seriously endangers people's health. About a quarter of the world's population is latent tuberculosis infection (LTBI). Once the body's immunity is weakened, LTBI develops into active tuberculosis, becoming a new source of infection and infecting more people. Globally, in 2019, approximately 10 million people were living with TB, 1.45 million people died from TB, and nearly half a million people developed rifampicin-resistant tuberculosis (RR-TB), 78% of whom were resistant to TB. Multi-drug tuberculosis (MDR-TB), especially XDR-TB, has become a new incurable disease. The three countries with the largest global burden are India (27%), China (14%) and the Russian Federation (8%). At presen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/685A61P31/06
CPCA61K31/685A61P31/06Y02A50/30
Inventor 戈宝学杨华王菲郭欣娅
Owner SHANGHAI PULMONARY HOSPITAL
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