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Novel use of pyrvinium pamoate in preparation of anti-mycobacterium tuberculosis drugs

A technology of mycobacterium tuberculosis and protozolin, which is applied in the direction of antibacterial drugs, pharmaceutical formulas, and medical preparations containing active ingredients, etc., can solve the problems of no reports on the anti-mycobacterium tuberculosis effect of protozoline, and avoid The effect of long approval time and broad application prospects

Inactive Publication Date: 2017-07-21
章晓联
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] There is no report about the anti-mycobacterium tuberculosis effect of Protrudoline

Method used

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  • Novel use of pyrvinium pamoate in preparation of anti-mycobacterium tuberculosis drugs
  • Novel use of pyrvinium pamoate in preparation of anti-mycobacterium tuberculosis drugs
  • Novel use of pyrvinium pamoate in preparation of anti-mycobacterium tuberculosis drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] [Example 1] 60 kinds of Mycobacterium smegmatis bacteriostatic agents were identified in 1280 Chinese drug libraries

[0032] In order to find new inhibitors of Mycobacterium tuberculosis, we used Mycobacterium smegmatis to screen 1280 kinds of drugs to screen new anti-tuberculosis drugs.

[0033] 1) Streak inoculation of Mycobacterium smegmatis strains on 7H10 solid medium, culture upside down at 37°C for 2 days, pick a single colony of Mycobacterium smegmatis and culture it in 7H9 liquid medium, and use enzyme Standard instrument A for the detection of bacteria 600 value;

[0034] 2) Then the bacterial concentration was diluted to 2.5×10 6 CFU / mL, add 200μl per well into 96-well cell culture plate;

[0035] 3) Utilize the 1280 kinds of drug libraries provided by MicroSource Discovery Systems, Inc. (Gaylordsville, CT, USA), and add the drugs to the 96-well cell culture plate through the Echo acoustic wave micropipette system (Labcyte, USA). The concentration duri...

Embodiment 2

[0040] [Example 2] 6 kinds of medicines have dose-dependent effect on the growth inhibition of Mycobacterium smegmatis

[0041] For the 9 drugs screened in Example 1, continue to use Mycobacterium smegmatis as a model bacterium, and add the above 9 drugs at different concentrations for detection.

[0042] 1) Streak inoculation of Mycobacterium smegmatis strains on 7H10 solid medium, culture upside down at 37°C for 2 days, pick a single colony of Mycobacterium smegmatis and culture it in 7H9 liquid medium, and use enzyme Standard instrument A for the detection of bacteria 600 value;

[0043] 2) Then the bacterial concentration was diluted to 2.5×10 6 CFU / mL, add 200μl per well into 96-well cell culture plate;

[0044] 3) Nine drugs with different concentrations (0, 0.5, 1, 2, 5, 10 μg / ml) were added to the 96-well cell culture plate, and after continuing to culture for 2 days, the A 600 value. Rifampicin was used as a positive control.

[0045] Such as figure 2As show...

Embodiment 3

[0046] [Example 3] Two drugs have dose-dependent growth inhibition of BCG and H37Ra

[0047] For the six drugs screened in Example 2, BCG and H37Ra were used as model bacteria, and different concentrations of the above six drugs were added for detection.

[0048] 1) Streak inoculation of BCG and H37Ra strains on 7H10 solid medium, culture upside down at 37°C for 30 days, pick BCG and H37Ra monoclonal colonies and culture them in 7H9 liquid medium, and use a microplate reader after 30 days A for the detection of bacteria 600 value;

[0049] 2) Then the bacterial concentration was diluted to 2.5×10 6 CFU / mL, add 5ml per tube to a 15ml centrifuge tube;

[0050] 3) Add the above 6 drugs at different concentrations (0, 0.5, 1, 2, 5, 10 μg / ml) respectively, and after 30 days, detect the A of the bacterial solution stimulated by different concentrations of drugs. 600 value. Rifampicin was used as a positive control.

[0051] The result is as image 3 As shown, only two drugs ...

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Abstract

The invention discloses a novel use of pyrvinium pamoate in preparation of anti-mycobacterium tuberculosis drugs. The invention is directed at a current situation that incidence and mortality of tuberculosis tend to rise due to high incidence of tuberculosis as well as serious drug resistance and multiple drug-resistant drugs caused by mycobacterium tuberculosis at present; 1280 drug libraries provided by MicroSource Discovery Systems, Inc. (USA) are utilized to identify that the pyrvinium pamoate has activities in inhibition of various mycobacterium tuberculosis and drug-resistant bacteria. The pyrvinium pamoate is a drug approved by FDA of US for treating enterobiasis and human ankylosing chromosome disease; the safety and pharmacokinetic properties of the pyrvinium pamoate are evaluated in humans and animals, so that the anti-mycobacterium tuberculosis effect can be detected directly in clinical practice, avoids a shortcoming of too long approval time of new drugs, and has a broad application prospect in treatment of tuberculosis and extrapulmonary tuberculosis (such as intestinal tuberculosis, etc.) caused by mycobacterium tuberculosis.

Description

technical field [0001] The invention relates to the field of drug anti-infection, in particular to the new application of protrudein in the preparation of anti-tuberculosis mycobacterium drugs. Background technique [0002] Tuberculosis is a chronic infectious disease that seriously endangers human health. Nearly one-third of people in the world are currently infected with Mycobacterium tuberculosis, which causes 130,000 deaths from tuberculosis every year, exceeding the total number of deaths from other infectious diseases. [0003] At present, there are a large number of drug-resistant bacteria in tuberculosis treatment, especially multidrug-resistant tuberculosis (MDR-TB, resistant to two or more first-line anti-tuberculosis drugs (isoniazid and rifampicin) at the same time), extensively drug-resistant The emergence of tuberculosis (XDR-TB, not only resistant to first-line anti-tuberculosis drugs, but also resistant to at least three second-line anti-tuberculosis drugs) h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4709A61K31/194A61P31/06
CPCA61K31/4709A61K31/194A61K2300/00
Inventor 章晓联关清
Owner 章晓联
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