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Use of compound AG120 or pharmaceutically acceptable salt thereof in preparation of drug for prevention or treatment of tuberculosis

A technology of AG120 and compound, applied in the direction of antibacterial drugs, dipeptide components, etc., can solve the problem of the use of unreported compound AG120 anti-tuberculosis drugs, and achieve the effect of effective drug support and inhibition of infection

Active Publication Date: 2019-01-18
SHANGHAI PULMONARY HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Therefore, none of the existing medical papers or books has reported that the compound AG120 can be used as an anti-tuberculosis drug.

Method used

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  • Use of compound AG120 or pharmaceutically acceptable salt thereof in preparation of drug for prevention or treatment of tuberculosis
  • Use of compound AG120 or pharmaceutically acceptable salt thereof in preparation of drug for prevention or treatment of tuberculosis
  • Use of compound AG120 or pharmaceutically acceptable salt thereof in preparation of drug for prevention or treatment of tuberculosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Db / Db (leptin receptor (Lepr) mutant) peritoneal primary macrophages of C57BL / 6 mice and DB / db mice were mixed with 1*10 5 Each cell / well was inoculated in a 48-well cell culture plate. After about 2 hours for the cells to adhere to the wall, the complete medium 1640 was removed, and then fresh complete medium was added to culture overnight. On the next day, 1 hour before infection, fresh 1640 containing 10% serum without double antibody was used to infect Mycobacterium tuberculosis (H37Rv) at a dose of MOI=5. After 2-3 hours of infection, discard the supernatant, then culture the cells with amikacin-containing medium for 2 hours, discard the supernatant and replace with 1640 containing 10% serum without double antibody and continue at 37°C for 5 %CO 2 Cells were cultured in the incubator for 24 h. Discard the supernatant and wash the cells with PBS, then lyse the cells with PBS containing 1% triton-100, take the cell lysate and spread it on a MiddleBook 7H10 agar pla...

Embodiment 2

[0033] The C57BL / 6 mice were divided into two groups, and the Db / db mice were divided into two groups, with 6 mice in each group, which were infected with Mycobacterium tuberculosis (H37Rv) by intranasal drip at a dose of 200 CFU / mouse for 1 week. Afterwards, the compound AG120 was orally administered continuously for 3 weeks at a dose of 2 mg / kg / day, and pure water was used as a blank control. The mice were sacrificed by dislocation of the cervical spine, and one lobe of the lung was taken out, fixed with 4% paraformaldehyde, paraffin sectioned, and H&E staining was performed to observe the pathological damage of the lung.

[0034] Experimental results such as figure 2 As shown, the pathological damage to the lungs of the mice treated with the compound AG120 was significantly reduced; therefore, the experimental results in this example show that the compound AG120 can effectively reduce the pathological damage to the lungs of the mice.

Embodiment 3

[0036] Take one-third of the mouse lung tissue after one week of infection and three weeks of administration in the above-mentioned Example 2, and grind it with 1 ml of PBS containing 1% triton-100, serially dilute, and take 10 -3 、10 -4 Spread 100ml of the tissue suspension evenly on the MiddleBook 7H10 agar culture plate containing amphotericin B, and then place it in a 37°C incubator for 2 to 3 weeks to complete the colony count. The specific results are as follows: image 3 shown.

[0037] The experimental results of this example confirmed that the compound AG120 significantly reduced the bacterial load of Mycobacterium tuberculosis in the lungs of mice.

[0038] Comprehensive analysis of the above examples shows that the compound AG120 can effectively inhibit the survival rate of Mycobacterium tuberculosis in vivo, thereby providing effective drug support for the treatment of tuberculosis.

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Abstract

The invention belongs to the technical field of pharmaceutical chemistry, and especially relates to use of compound AG120 or pharmaceutically acceptable salt thereof in preparation of drug for prevention or treatment of tuberculosis, and a pharmaceutical composition for preventing or treating tuberculosis. The compound AG120 can effectively inhibit the infection of tuberculosis bacillus, thereby providing effective drug support for the prevention or treatment of tuberculosis. Therefore, the present invention discloses compound AG120 which can be used as a lead compound for preventing or treating tuberculosis, and has the activity of anti-tuberculosis bacteria and drug-resistant tuberculosis bacteria, and is particularly suitable for preventing or treating tuberculosis, thus having wide clinical application prospect and great market potential.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and particularly relates to the use of compound AG120 or a pharmaceutically acceptable salt thereof in the preparation of medicines for preventing or treating tuberculosis, and a pharmaceutical composition for preventing or treating tuberculosis. Background technique [0002] Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis infection. Tuberculosis usually causes an infection of the lungs, but can also infect other parts of the body; also, most infected people are asymptomatic. This type of infection is called latent TB infection. If proper treatment is not given at this time, 10% of patients with latent infection will develop For open tuberculosis, its fatality rate is about 50%. [0003] Tuberculosis is known to affect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis). Extrapulmonary TB (ie, TB that occurs in organs oth...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/05A61P31/06
CPCA61K38/05A61P31/06
Inventor 戈宝学陈建霞刘峰刘海鹏李蒿蒿王菲刘忠华唐芬黄晓辰王洁
Owner SHANGHAI PULMONARY HOSPITAL
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