32 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.

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 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.

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.

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 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 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 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.

Clofazimine (CFZ) is an important component of a full oral pharmaceutical regimen recommended by the World Health Organization (WHO) for the treatment of multidrug resistant tuberculosis (MDR-TB). However, the lack of the divisible oral dosage form has limited the use of the medicament in pediatric populations that may require reduced doses to reduce the likelihood of adverse drug events. Pediatric friendly CFZ mini-tablets prepared from micronized powder via direct compression at relatively high drug loading provide suitable dosage forms for 6-month-old children as well as patients with whole capsules or difficult tablet swallowing.

The present invention provides a monoclonal antibody targeting Mycobacterium tuberculosis MctB, as well as a preparation method and application. The monoclonal antibody comprises a heavy chain variable region and a light chain variable region. The HCDR1-3 sequences of the heavy chain variable region are shown in SEQ ID NOs: 1, 2, and 3, and the LCDR1-3 sequences 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 for the prevention of tuberculosis.

The invention discloses a guaiane type sesquiterpene compound as well as a preparation method and application thereof, and belongs to the technical field of chemical medicines. The invention provides a guaiane type sesquiterpene compound with a novel structure, which is extracted from lactarius deliciosus sporocarp, can well inhibit the activity of mycobacterium tuberculosis, especially has an excellent inhibition effect on single-drug-resistant mycobacterium tuberculosis and multi-drug-resistant mycobacterium tuberculosis, and can be used for preparing medicines for treating lactarius deliciosus. The guaiane type sesquiterpene compound is expected to be used for treating tuberculosis, especially drug-resistant tuberculosis, so that the variety of drugs for treating tuberculosis, especially drug-resistant tuberculosis, is expanded, and the application range of lactarius deliciosus extract is also expanded.

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 invention discloses a rapid inactivation device for harmless treatment of sputum of a drug-resistant tuberculosis patient. The rapid inactivation device comprises a treatment bottle, a heating base and a flow guide cover, the upper portion of the treatment bottle is of a conical structure, the treatment bottle is connected with the flow guide cover in an inserted mode, a shielding assembly is arranged on one side of the treatment bottle and comprises a groove, the groove is located in the side wall of the treatment bottle, a connecting shaft is rotationally connected between the groove and the treatment bottle, and a connecting rod is rotationally connected to the connecting shaft. A heating pad is connected to the side wall of the inner wall of the treatment bottle, the heating arm is connected with a heating base, a controller is arranged on the heating base, and an adjusting knob is connected to the controller. Compared with the prior art, the sputum sterilizing device has the advantages that the heating temperature can be conveniently adjusted, sputum can be conveniently sterilized through the flow guide cover, and therefore treatment is more convenient.

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.