42 results about "Resistant tuberculosis" patented technology

The invention provides a compound as shown in a formula (I), a stereoisomer thereof, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a crystal form thereof, an isotope derivative thereof, a prodrug thereof and a metabolite thereof. The solvate or hydrate of the compound can be used for preparing a pharmaceutical composition for treating and / or preventing diseases related to mycobacterium tuberculosis and / or nontuberculous mycobacterium. The compound provided by the invention has an excellent bactericidal effect and strong specificity, has no cross resistance with the existing antituberculosis drugs, and provides a breakthrough direction for treatment of drug-resistant tuberculosis.

The present invention provides a clofazimine ethanol crystalline compound, its preparation method, application, and pharmaceutical composition, relating to the field of biomedicine. The clofazimine ethanol crystalline compound provided by the present invention has a small size and a relatively large surface area. When used as a pharmaceutical, it has a high dissolution rate and a high in vivo absorption rate, enabling faster achievement of higher blood drug concentrations and providing enhanced therapeutic effects against diseases such as leprosy and drug-resistant tuberculosis.

The present invention provides a CRISPR system and a kit for detecting drug-resistant tuberculosis, which belong to the technical field of drug-resistant tuberculosis detection. The CRISPR system includes AaCas12b and sgRNA; the sgRNA includes a first sgRNA targeting the tuberculosis-specific sequence IS6110; and also includes a second and a third sgRNA targeting the drug-resistant tuberculosis rpoBS531L and / or katGS315T mutation sites. The present invention is based on the Crispr-AaCas12b system, targeting the tuberculosis-specific sequence IS6110 and the most common mutation sites of drug-resistant tuberculosis. By selecting PAM and adjusting the length of the sgRNA spacer binding region and artificially introducing base mismatches, Crispr-AaCas12b can specifically recognize drug-resistant mutation sites and does not recognize wild-type sequences; drug-resistant tuberculosis is quickly and accurately detected by fluorescence signal monitoring.

A kit for detecting drug-resistant tuberculosis, includes: detection reagents, configured to perform quantitative detection on 17 serum metabolites of patients with tuberculosis, the 17 serum metabolites comprising: taurine, homocysteine, uric acid, ascorbic acid, suberylglycine, uridine, dopamine 4-sulfate, inosinic acid, glyceraldehyde phosphate, [3-methoxy-4-(phosphoryl)phenyl]carbonyl sulfonic acid, nuclomedone, n4-cyclopropyl-6-(2,3-dichlorophenyl)-1,2,3,4-tetrahydropyrimidine-tetrachlorophthalic anhydride, malotilate, fulvic acid, and L-neopterin.

The invention relates to a drug-resistant tuberculosis early warning method and kit for heterogeneity drug resistance semi-quantitative detection. The early warning method comprises the following steps: designing an amplification primer, a retardation probe and an extension primer for a target gene; extracting DNA of an object to be detected; adding the amplification primer and the retardation probe into a nucleic acid amplification system, and carrying out nucleic acid amplification on the DNA of the object to be detected; digesting an amplification product by using shrimp alkaline phosphatase (SAP); adding the extension primer into a system subjected to SAP digestion, and carrying out single base extension; and finally, carrying out resin desalination on the extension product, and detecting by using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The invention also discloses a kit, which comprises an amplification primer, a retardation probe, an extension primer, an amplification reaction solution, a digestion reaction solution, an extension reaction solution, resin and a chip. According to the invention, trace mutation sites can be rapidly, efficiently and simply detected; and the proportion of mutation sites of a sample can be semi-quantitatively detected.

The present disclosure provides small molecule anti-tuberculosis agents and pharmaceutical compositions comprising the anti-tuberculosis agents. The disclosure further provides a method of treating tuberculosis, including drug-resistant tuberculosis, in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the anti-tuberculosis agent.

The present invention relates to a co-administered formulation for alleviating anti-tuberculosis drug-induced toxicity comprising dead cells, and a pharmaceutical composition for preventing or treating tuberculosis comprising same. By co-administering Lactobacillus sakei CVL-001 or Lactobacillus reuteri NCHBL-005 as the dead cells with the anti-tuberculosis drug, the present invention exhibits excellent effects in alleviating drug toxicity (hepatotoxicity and nephrotoxicity) caused by the anti-tuberculosis drug, thereby increasing drug adherence of the anti-tuberculosis drug to obtain the effect of inhibiting the emergence of multidrug-resistant tuberculosis and recurrence of tuberculosis. In addition, the present invention can be used as an adjuvant for co-administration with drugs that have high efficacy despite significant side effects, such as bedaquiline or linezolid, with the expected effect of reducing the treatment period of tuberculosis, thereby being effectively used in the treatment process of tuberculosis.

The invention belongs to the technical field of biological medicine, and particularly relates to application of Sulfaclozine and salt thereof in resisting mycobacterium tuberculosis infection. The invention finds that Sulfaclozine has good bacteriostatic activity on mycobacterium tuberculosis standard strains and multi-drug-resistant tuberculosis clinical isolates, has good safety within the concentration of 40 [mu] M, and is expected to become a novel mycobacterium tuberculosis infection resisting drug.

A set of serum metabolic biomarkers and detection kit for detecting drug-resistant tuberculosis are provided. The set of the serum metabolic biomarkers includes 17 serum metabolic biomarkers. The 17 serum metabolic biomarkers are verified to be associated with tuberculosis based on the level changes of these biomarkers. The 17 metabolites includes taurine, homocysteine, uric acid, ascorbic acid, suberylglycine, uridine, dopamine 4-sulfate, inosinic acid, glyceraldehyde phosphate, [3-methoxy-4-(phosphoryl)phenyl]carbonyl sulfonic acid, nuclomedone, n4-cyclopropyl-6-(2,3-dichlorophenyl)-1,2,3,4-tetrahydropyrimidine-2,4-diimine, 1-[2-chlorine-2-(2,4-dichlorophenyl)ethenyl]-1,2,4-triazole, tetrachloro-phthalic anhydride, malotilate, fulvic acid, and L-neopterin. The serum metabolic biomarkers and detection kit for detecting drug-resistant tuberculosis can assist doctors in accurately diagnosing the disease, which is of great significance for the diagnosis and mass screening for drug-resistant tuberculosis.

In one aspect, the disclosure relates to compounds effective in the treatment of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis as well as drug-sensitive tuberculosis, methods of making the same, pharmaceutical compositions comprising the same, and methods of treating bacterial infections caused by Mycobacterium tuberculosis using the same. In an aspect, the compounds and pharmaceutical compositions are not cytotoxic. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

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 method for constructing a model for performing treatment outcome grouping on AIDS (acquired immune deficiency syndrome) and phthisis patients and application of the method. The invention provides a method for constructing a model for performing anti-tuberculosis treatment outcome grouping on AIDS (Acquired Immune Deficiency Syndrome) and pulmonary tuberculosis patients, which comprises the following steps of: taking five specific index data of known AIDS and pulmonary tuberculosis patient groups with different anti-tuberculosis treatment outcomes as training samples; training a model for performing anti-tuberculosis treatment outcome grouping on the AIDS and pulmonary tuberculosis patients; the five specific indexes are CAR, extrapulmonary tuberculosis, other pulmonary infections, lung cavities and CD4 + T lymphocyte count. According to the method, clinical doctors can quickly identify AIDS and tuberculosis patients with high treatment failure risk, personalized management is carried out on the AIDS and tuberculosis patients, the method is of great importance to reduction of the occurrence rate of retreatment and drug-resistant tuberculosis, and a new strategy is provided for precise treatment.

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.

The invention belongs to the technical field of disease prognosis prediction, and provides a prognosis prediction method for multidrug-resistant tuberculosis in order to solve the problem that an existing prognosis monitoring method for a multidrug-resistant tuberculosis patient has certain limitation. By integrating handmade radiology features and deep learning derived imaging features extracted from baseline, two-month and six-month continuous CT scanning, processing data by adopting a gated recurrence unit (GRU) network, and combining with a multi-drug-resistant tuberculosis prognosis prediction system, a treatment result of a multi-drug-resistant tuberculosis patient is predicted. According to the prediction method provided by the invention, the high-risk patient can be accurately identified in the early stage of the treatment process, and powerful support is provided for personalized treatment decision making, intervention opportunity optimization and reasonable public health resource allocation. Moreover, the kit has higher sensitivity and specificity, and the potential in the aspects of multi-drug-resistant tuberculosis treatment result prediction and risk stratification accuracy is improved.

The present invention belongs to the field of biomedicine, and specifically relates to a pharmaceutical composition for treating Mycobacterium tuberculosis infection. The invention proves that cysE is involved in reducing oxidative stress, thereby regulating the virulence and drug resistance of M.tb. Targeting cysE, especially through synergistic effects with CFZ and BDQ, can enhance the treatment of drug-resistant tuberculosis. C1 is a CysE inhibitor, and treatment with C1 alone does not affect the growth of Mycobacterium tuberculosis H. 37 The survival rates of RvWT and ΔcysE strains were significantly lower, and the addition of C1 did not affect the WT's sensitivity to BDQ. However, the addition of C1 significantly increased the WT's sensitivity to CFZ and the combination of BDQ and CFZ, while the ΔcysE strain did not show such an enhancement. This suggests that the serine acetyltransferase CysE is a target for the design of antimycobacterial drugs, and that the CysE inhibitor C1 can synergize with CFZ and BDQ to effectively eliminate Mycobacterium tuberculosis.

The present invention relates to an application of a combined preparation of cefathiamidine and clavulanic acid in the treatment of tuberculosis. Cefathiamidine and clavulanic acid are used in combination to significantly improve the activity against Mycobacterium tuberculosis. It is verified by in vitro experiments that the β-lactamase inhibitor clavulanic acid significantly improves the anti-tuberculosis effect of cefathiamidine. The combined preparation shows significant advantages in inhibiting the growth of Mycobacterium tuberculosis and has a strong inhibitory effect on drug-resistant strains. At the same time, the combined preparation shows lower cytotoxicity in in vitro experiments and shows better safety. In addition, the combined preparation has potential application prospects in the treatment of drug-resistant tuberculosis and can effectively supplement existing tuberculosis treatment regimens.

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 invention relates to an application of a cefathiamidine and clavulanic acid combined preparation in tuberculosis treatment, cefathiamidine and clavulanic acid are combined for use, and the activity of resisting mycobacterium tuberculosis is remarkably improved. In-vitro experiments prove that the beta-lactamase inhibitor clavulanic acid remarkably improves the antituberculous effect of cefathiamidine, and the combined preparation shows remarkable advantages in the aspect of inhibiting the growth of mycobacterium tuberculosis and has a relatively strong inhibiting effect on drug-resistant strains. Meanwhile, the combined preparation shows relatively low cytotoxicity in an in-vitro experiment, and shows relatively good safety. In addition, the combined preparation has a potential application prospect in treatment of drug-resistant tuberculosis, and can effectively supplement the existing tuberculosis treatment scheme.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a compound in resisting mycobacterium tuberculosis infection. It is found that Haloxon has good bacteriostatic activity on mycobacterium tuberculosis standard strains and multi-drug-resistant tuberculosis clinical isolates, the MIC of Haloxon on the mycobacterium tuberculosis standard strains can reach 10 [mu] M, the MIC distribution of Haloxon on the multi-drug-resistant tuberculosis clinical isolates is 1.25-20 [mu] M, and Haloxon does not have obvious toxicity and is expected to become a new anti-mycobacterium tuberculosis infection drug.

The invention relates to the technical field of nucleic acid detection, and discloses an RCA-CRISPR multiple mutation detection system for drug-resistant tuberculosis screening, which comprises a sample processing module, an RCA isothermal amplification module, a CRISPR-Cas multiple detection module and a signal output module, and solves the problems that when the existing detection system is used, the detection is often performed through a single mutation detection system, and the detection time is short. The detection method cannot meet the multi-target screening requirement of the drug-resistant tuberculosis, and a multi-channel detection platform has the problems of complex operation, high cost and the like, and is not beneficial to subsequent screening and detection.

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 provides an application of (5R, 6E)-5-hydroxy-17-diphenyl-6-heptene-3-ketone in preparation of a medicine for treating or preventing drug-resistant mycobacterium tuberculosis infection, the MIC (minimal inhibitory concentration) of the (5R, 6E)-5-hydroxy-17-diphenyl-6-heptene-3-ketone to mycobacterium tuberculosis H37Rv, rifampicin drug-resistant strains, levofloxacin drug-resistant strains and bedaquiline drug-resistant strains is 2g / mL, and the MIC (minimal inhibitory concentration) of the (5R, 6E)-5-hydroxy-17-diphenyl-6-heptene-3-ketone to mycobacterium tuberculosis H37Rv, rifampicin drug-resistant strains, levofloxacin drug-resistant strains and bedaquiline drug-resistant strains is The core problem of tuberculosis with multiple drug resistance and wide drug resistance is solved, and an alternative treatment approach is provided.

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 invention discloses application of eupatilin and a pharmaceutical composition, and relates to the technical field of biological medicines, and the medicine is used for treating diseases caused by mycobacterium tuberculosis or nontuberculous mycobacterium infection. According to the application disclosed by the invention, the research finds that the eupatilin has a human macrophage level anti-tuberculosis effect and has an effect of inhibiting intracellular survival of mycobacterium tuberculosis or nontuberculous mycobacterium at a macrophage level for the first time, which indicates that the eupatilin has an application value as a drug for treating multidrug-resistant tuberculosis; the compound can be used as a novel anti-tuberculosis or anti-nontuberculous mycobacterium medicine.

The present invention provides a protective monoclonal antibody targeting Mycobacterium tuberculosis OmpA, as well as a preparation method and application. The monoclonal antibody comprises a heavy chain variable region and a light chain variable region. The sequences of HCDR1-3 of the heavy chain variable region are shown in SEQ ID NOs: 1, 2, and 3, and the sequences of LCDR1-3 of the light chain variable region are shown in SEQ ID NOs: 4, 5, and 6. The provided antibody can be used to treat tuberculosis, especially drug-resistant tuberculosis, and can also be used to prevent 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.