16 results about "Resistant tuberculosis" patented technology

The application discloses application of elvitegravir in preparation of an inhibitor of mycobacterium tuberculosis or non-tuberculous mycobacteria, and relates to the technical field of biological medicine.The application discloses, for the first time, that elvitegravir has the effect of inhibiting intracellular survival of mycobacterium tuberculosis or non-tuberculous mycobacteria at the level of macrophages, has the effect of anti-tuberculosis at the level of macrophages, and can be applied to preparation of an inhibitor of mycobacterium tuberculosis or non-tuberculous mycobacteria.The application also discloses that the anti-tuberculosis effect of elvitegravir at the level of macrophages is not the direct action of antibiotics on bacteria, but the inhibition of intracellular survival of tubercle bacillus by targeting and regulating host immune response, so that elvitegravir also has the potential of an immunomodulator, can realize the anti-tuberculosis effect by regulating the immune response of the body to tubercle bacillus infection, and is not affected by drug resistance of mycobacterium tuberculosis, and has a good treatment effect on multidrug-resistant tuberculosis.

The invention discloses a temperature-sensitive gel preparation entrapped with mycobacterium tuberculosis bacteriophage sustained-release microspheres and application of the temperature-sensitive gel preparation, and belongs to the technical field of biological medicine, the preparation comprises a temperature-sensitive gel matrix and targeted ROS sensitive sustained-release microspheres dispersed in the temperature-sensitive gel matrix; the targeted ROS sensitive sustained release microsphere comprises a mycobacterium tuberculosis phage, a composite targeted unit and an ROS sensitive monomer. According to the preparation disclosed by the invention, a composite targeting-ROS response drug release-temperature-sensitive retention three-in-one anti-multi-drug-resistant tuberculosis gel system is constructed, a closed loop of precise targeting aggregation-on-demand directional drug release-long-acting local effect is formed by the three components in a synergistic manner, efficient bacteriostasis, anti-inflammatory repair and medication safety are considered, and a reference scheme is provided for treatment of tuberculosis infection.

This invention discloses a strategy for rapid detection of isoniazid resistance in Mycobacterium tuberculosis based on multiplex polymerase chain reaction (Multiplex PCR) using local rTth DNA polymerase and interpretation of amplification patterns. This strategy utilizes a specific primer combination that allows simultaneous amplification of the control fragment and the target fragment of the katG gene codon 315 mutation in a single PCR reaction. The amplification products are analyzed by 1% (w / v) agarose gel electrophoresis and interpreted based on the resulting DNA banding pattern to distinguish sensitive isolates, isolates carrying the katG315 mutation causing isoniazid resistance, and invalid test results. The use of local rTth DNA polymerase provides an alternative thermostable enzyme to support national diagnostic raw material independence without changing the detection principle.This strategy allows for rapid identification of katG315 mutations associated with isoniazid resistance without the need for DNA sequencing or further molecular analysis. The invention provides a simple, rapid, specific, easily interpretable, and cost-effective molecular diagnostic method to support the early detection of isoniazid-resistant tuberculosis.

The invention belongs to the field of biological medicines, and particularly relates to application of dapinustat in preparation of a medicine for preventing and / or treating mycobacterium tuberculosis infection. In-vitro experiments prove that dapunostat has remarkable inhibitory activity on a mycobacterium tuberculosis standard strain, the minimum inhibitory concentration (MIC) is 1 mu g / mL, and the bactericidal effect of dapunostat under high bacterial load is superior to that of rifampicin. The dapinustat and the rifampicin have a synergistic effect. When dapunostat is combined with first-line antituberculosis drugs such as isoniazide, bedaquiline and ethambutol for use, drug effects are added. In addition, the dapunostat has no obvious toxicity to THP-1 human macrophages under an effective concentration. According to the invention, the new application of dapinustat in resisting mycobacterium tuberculosis is found for the first time, a brand new candidate drug and a drug combination scheme with known safety are provided for treatment of tuberculosis, especially drug-resistant tuberculosis, and the dapinustat has important clinical application value and development prospect.

The application belongs to the technical field of biology and particularly relates to screening and application of a rifampicin-resistant tuberculosis urine metabolic marker. The urine metabolic marker comprises 20 metabolites. After verification, the level change of the 20 metabolites is indeed related to rifampicin-resistant tuberculosis. The application further provides a screening method of a rifampicin-resistant tuberculosis metabolic marker, a diagnostic rifampicin-resistant tuberculosis disease detection kit and a rifampicin-resistant tuberculosis disease diagnosis model. The 20 urine metabolic markers screened are used for rifampicin-resistant tuberculosis detection, have high accuracy and are of great significance for diagnosis of rifampicin-resistant tuberculosis.

The invention discloses a PCR-CRISPR method and a PCR-CRISPR system for integrated detection of drug-resistant sites of mycobacterium tuberculosis and rifampicin. Specifically, the invention discloses a PCR-CRISPR method for in-vitro non-diagnostic and non-therapeutic integrated detection of mycobacterium tuberculosis and rifampicin drug-resistant mutation sites, and the method comprises the following steps: (s1) providing a sample to be detected, and extracting total DNA; (s2) pushing nucleic acid liquid containing the total DNA into a first reaction chamber, and carrying out asymmetric PCR reaction to obtain a first fluorescence signal; (s3) pushing a PCR amplification product in the step (s2) into a second reaction chamber, carrying out CRISPR reaction in the second reaction chamber, and obtaining a second fluorescence signal for judging whether the target sequence exists or not; and (s4) combining and analyzing the first fluorescence signal and the second fluorescence signal to obtain a detection result of the mycobacterium tuberculosis and rifampicin drug-resistant mutation site. The method disclosed by the invention is high in detection sensitivity, convenient to operate and low in cost, and can be used for effectively screening tuberculosis and multidrug-resistant tuberculosis.

This invention provides a compound of formula (I), its stereoisomers, its optical isomers, its pharmaceutically acceptable salts, its crystal form, its isotopic derivatives, its prodrug, its metabolites, its solvates, or its hydrates for the preparation of pharmaceutical compositions for the treatment and / or prevention of diseases associated with Mycobacterium tuberculosis and / or non-tuberculous mycobacteria. The compounds of this invention exhibit excellent bactericidal effects and high specificity, showing no cross-resistance with existing anti-tuberculosis drugs, thus providing a breakthrough direction for the treatment of drug-resistant tuberculosis.

This invention discloses the use of a combination of nitroimidazole derivatives in the preparation of drugs for the prevention and treatment of drug-resistant tuberculosis, belonging to the field of biomedical technology. This invention fills the clinical research gap regarding the use of combination drugs of nitroimidazole derivatives in the prevention and treatment of drug-resistant tuberculosis, providing a method for its application in the preparation of drugs for this purpose. This invention demonstrates good therapeutic effects against drug-resistant tuberculosis by combining nitroimidazole derivatives with various other anti-tuberculosis drugs, and shows promise as a new drug for the prevention and treatment of drug-resistant tuberculosis.

This invention discloses the application of erteiravir in the preparation of inhibitors for Mycobacterium tuberculosis or non-tuberculous mycobacteria, relating to the field of biomedical technology. This invention discloses for the first time that erteiravir has the effect of inhibiting the intracellular survival of Mycobacterium tuberculosis or non-tuberculous mycobacteria at the macrophage level, exhibiting anti-tuberculosis activity at the macrophage level, and can be applied to the preparation of inhibitors for Mycobacterium tuberculosis or non-tuberculous mycobacteria. This invention also discloses that the anti-tuberculosis effect of erteiravir at the macrophage level does not act directly on bacteria as an antibiotic, but rather inhibits the intracellular survival of Mycobacterium tuberculosis by targeting and regulating the host immune response. Therefore, erteiravir also has the potential as an immunomodulator, achieving anti-tuberculosis effects by regulating the body's immune response to Mycobacterium tuberculosis infection without being affected by drug resistance of Mycobacterium tuberculosis, and has a good therapeutic effect on multidrug-resistant tuberculosis.

The present application belongs to the technical field of disease prognosis prediction, and aims at the problem that the existing prognosis monitoring method for multidrug-resistant tuberculosis patients has certain limitations. The present application provides a multidrug-resistant tuberculosis prognosis prediction method, which integrates the manually made radiology features and the deep learning derived imaging features extracted from the baseline, two-month and six-month continuous CT scans, adopts a gated recurrent unit (GRU) network to process the data, and combines a multidrug-resistant tuberculosis prognosis prediction system to predict the treatment results of multidrug-resistant tuberculosis patients. The prediction method provided by the present application can accurately identify high-risk patients in the early stage of the treatment process, and provides strong support for personalized treatment decisions, optimization of intervention timing and reasonable allocation of public health resources. Moreover, the present application has higher sensitivity and specificity, and improves the potential of the accuracy of multidrug-resistant tuberculosis treatment result prediction and risk stratification.

The invention discloses an application of a compound JQB-22 or a pharmaceutically acceptable salt thereof in preparation of antituberculosis drugs, and relates to the technical field of biological medicines. It is found that the compound JQB-22 has the effect of inhibiting intracellular survival of tubercle bacillus at the macrophage level, the anti-tuberculosis effect can be remarkably enhanced by regulating and controlling host immunity, and compared with a traditional first-line anti-tuberculosis drug ethambutol, the compound JQB-22 shows better control over the load of tubercle bacillus in lung tissue. The compound JQB-22 provided by the invention has the potential of being developed as an antituberculous drug. The invention provides an innovative research direction and a preclinical candidate drug for solving the treatment difficulty of the drug-resistant tuberculosis.

The application discloses application of isoschaftoside and a pharmaceutical composition, relates to the technical field of biological medicine, and the medicine is used for treating diseases caused by mycobacterium tuberculosis or non-tuberculous mycobacterial infection. The application discloses that isoschaftoside has human macrophage level anti-tuberculosis effect for the first time, and the isoschaftoside has the effect of inhibiting intracellular survival of mycobacterium tuberculosis or non-tuberculous mycobacteria at the macrophage level, which indicates that the isoschaftoside has the application value as a medicine for treating multidrug-resistant tuberculosis, and the isoschaftoside can be used as a novel anti-tuberculosis or anti-non-tuberculous mycobacterial medicine.

The invention discloses an application of a CD2 antagonist in preparation of an antituberculous drug. The preparation method comprises the following steps: targeting CD2 molecules on the surface of an NK cell by virtue of a high-affinity CD2 antagonist, synergistically strengthening the degranulation of the NK cell and the release of antibacterial peptide (granulysin, beta-defensin 4), and directly destroying the completeness of a cell membrane and a cell wall of mycobacterium tuberculosis (Mtb), so that the extracellular rapid sterilization is realized; in an in-vitro NK cell-macrophage co-culture model, the number of intracellular CFUs is remarkably reduced through the strategy; meanwhile, the mitochondrial membrane potential and metabolic activity of the NK cells are optimized, and the lasting effect is maintained; in a peripheral blood model of a tuberculosis patient, the strategy significantly amplifies Mtb-induced infected macrophage death, reduces intracellular bacterial load, integrally improves the ability of immune cells to remove infected macrophages, and provides a safe, efficient and convertible molecular intervention entry point for precise immunotherapy of tuberculosis, especially multidrug-resistant tuberculosis.

The application discloses application of Rv-NG-14 gene and coded protein thereof as a multidrug-resistant tuberculosis biomarker, the nucleotide sequence of the gene is SEQ ID NO:1, and the amino acid sequence of the coded protein is SEQ ID NO:2. The gene is verified to be normally expressed in Mycobacterium tuberculosis through multi-omics verification, and it is found through detection of 50 clinical strains that the transcriptional expression level of the gene in a multidrug-resistant group is significantly lower than that in a drug-sensitive group (p=0.002), and there is no significant difference between a single drug-resistant group and the drug-sensitive group. The application first finds out the multidrug-resistant tuberculosis marker value of the gene, and the gene can be used for preparing products such as detection kits and test strips, so that rapid diagnosis of multidrug-resistant tuberculosis is realized, a new target point is provided for research and development and screening of anti-multidrug-resistant tuberculosis drugs, and the application prospect is wide in clinical application.

The invention discloses combined application of glutamine and a TIGIT inhibitor in preparation of a medicine for resisting mycobacterium tuberculosis infection. According to the invention, by jointly supplementing exogenous glutamine and blocking TIGIT, the NK cell function can be cooperatively rescued from dual dimensions of metabolic supplement and signal release. Experiments prove that the drug combination shows a remarkable synergistic amplification effect in the aspects of enhancing the lethality of NK cells to infected target cells, reducing the number of intracellular bacteria, recovering mitochondrial quality, membrane potential and ATP level and the like. The glutamine is endowed with new application in tuberculosis host-oriented treatment, a brand-new precise immunometabolism treatment scheme is provided for patients with drug-resistant tuberculosis or poor curative effects of traditional anti-tuberculosis drugs, and the glutamine has a good clinical transformation prospect.

The invention discloses an application of epothilone and rifampicin in preparation of a synergistic anti-tuberculosis drug, and belongs to the technical field of anti-tuberculosis drugs. The core of the application is that the epothilone and the rifampicin are combined for use, and through the synergistic effect of the epothilone and the rifampicin, the bactericidal activity of the rifampicin is remarkably enhanced, the minimum inhibitory concentration of the rifampicin is reduced, and development of drug resistance of mycobacterium tuberculosis is effectively inhibited. The invention also provides a pharmaceutical preparation and a medicine box containing the two active components. According to the combined application scheme, the clinical dosage of rifampicin can be reduced, so that adverse reactions such as hepatotoxicity of the rifampicin are reduced, and the compound is suitable for treating sensitive and rifampicin-resistant tuberculosis and has important clinical value and application prospects.