New application of pyrazolo[1,5-a]pyridine compounds and a composition for treating Mycobacterium abscessus infection
A technology of mycobacteria and pyrazolo, which is applied in the direction of medical preparations containing active ingredients, antibacterial drugs, organic active ingredients, etc., to achieve prolonged treatment cycle, fast onset, and overcome the problem of induced drug resistance in clinical treatment Effect
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experiment example 1
[0049] Experimental example 1, graded inhibitory concentration experiment of CFZ and TB47
[0050] 1. Experimental grouping
[0051] The graded concentration of TB47 is 12.5μg / mL, 6.25μg / mL, 3.12μg / mL, 1.56μg / mL, 0.78μg / mL, 0μg / mL;
[0052] The graded concentration of CFZ (CFZ) is 10μg / mL, 5μg / mL, 2.5μg / mL, 1.25μg / mL, 0.62μg / mL, 0μg / mL;
[0053] According to the graded concentrations of the above two drugs, they are combined and administered in combination one by one;
[0054] The CFZ and TB47 used above were dissolved in dimethyl sulfoxide (DMSO) for use.
[0055] 2. Experimental steps
[0056] (1) Mab cultivation
[0057] Insert the self-luminescent Mab into 5mL 7H9 liquid medium for culture, add glass beads to break up, and cultivate to the OD of the bacterial solution 600 When reaching 0.6-0.8, dilute the bacterial solution by 10 -6 , take 0.5mL plated 7H11 solid medium, and culture at 37°C for 14 days; pick a single colony from the plate and use a luminescence detec...
experiment example 2
[0062] Experimental example 2. Synergistic experiment of low concentration TB47 on CFZ anti-Mab
[0063] 1. Experimental grouping
[0064] Utreated group: give equal volume of DMSO as a control
[0065] TB47-0.078 group: administer TB47 at a concentration of 0.078 μg / mL;
[0066] CFZ-2 group: administer CFZ at a concentration of 2 μg / mL;
[0067] CFZ-2+TB47-0.02 group: the administration concentration is TB47 0.02μg / mL and CFZ 2μg / mL;
[0068] CFZ-2+TB47-0.078 group: the administration concentration is TB47 0.078μg / mL and CFZ 2μg / mL;
[0069] The CFZ and TB47 used above were dissolved in DMSO for use.
[0070] 2. Experimental steps
[0071] (1) Mab cultivation
[0072] Insert the self-luminescent Mab into 5mL 7H9 liquid medium for culture, add glass beads to break up, and cultivate to the OD of the bacterial solution 600 When reaching 0.6-0.8, dilute the bacterial solution by 10 -6 , take 0.5mL plated 7H11 solid medium, and culture at 37°C for 14 days; pick a single co...
experiment example 3
[0077] Experimental example 3, detection of intracellular activity of the composition of the present invention
[0078] 1. Experimental grouping
[0079] Untreated group: given an equal volume of dimethyl sulfoxide as a control;
[0080] TB47 group: administer TB47 at a concentration of 1 μg / mL;
[0081] CFZ group: administer CFZ at a concentration of 2 μg / mL, which is the minimum inhibitory concentration in vitro;
[0082] CLR group: CLR was administered at a concentration of 4 μg / mL, which was the minimum inhibitory concentration in vitro;
[0083] ROX group: Administer ROX at a concentration of 4 μg / mL, which is the minimum inhibitory concentration in vitro;
[0084] CFZ+TB47 group: CFZ 1 μg / mL and TB47 2 μg / mL;
[0085] CLR+AMK group: administration of CLR4μg / mL and AMK8μg / mL;
[0086] CFZ+TB47+CLR group: CFZ 1 μg / mL, TB47 2 μg / mL and CLR 4 μg / mL;
[0087] CFZ+TB47+ROX group: CFZ 1 μg / mL, TB47 2 μg / mL and ROX 4 μg / mL;
[0088] The CLR, ROX, CFZ, and TB47 used above ...
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