28 results about "Antitubercular Agent" 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 invention belongs to the technical field of medicines, and particularly discloses application of fibronectin 1 (FN1) in treatment of mycobacterial infection. The invention finds that the FN1 has new application, and the survival of mycobacteria can be inhibited when the FN1 is independently applied; in a mycobacterium infection model, after the FN1 protein is exogenously added, the number of mycobacteria in macrophages is remarkably reduced; on the contrary, after the FN1 is knocked down, the number of mycobacteria in the macrophage is obviously increased. Further mechanism research shows that the FN1 affects release of reactive oxygen species (ROS) and cytokines by regulating a PI3K / AKT signaling pathway, and further removes mycobacteria in macrophages. From the perspective of host immunity, the invention discloses a mechanism that FN1 affects ROS (reactive oxygen species) and inflammatory response by regulating a PI3K / AKT signal channel so as to inhibit mycobacteria, and a new medicine is provided for treatment of mycobacteria infection. On the basis, FN1 can be independently used or combined with first-line antituberculosis drugs, and a new means is provided for solving the problem of drug resistance in mycobacterium infection treatment.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a compound NSC348884 in preparation of a medicine for resisting mycobacterium tuberculosis. Experimental results show that the NSC348884 has remarkable in-vitro bacteriostatic activity on standard strains and clinical isolates of mycobacterium tuberculosis. The MIC of the strain to a standard strain is 2 [mu] g / mL, and the MIC distribution of the strain to a clinical isolated strain is 0.5-4 [mu] g / mL. Further bacteriostatic activity evaluation shows that after the mycobacterium tuberculosis is treated by NSC348884 (1 [mu] g / mL) for 3 days, the growth of the mycobacterium tuberculosis is obviously inhibited, and the inhibition rate is 41.82% + / -10.14%. Compared with a DMSO control group, the CFU is reduced by about 0.24 log. The discovery prompts that NSC348884 has the potential of being developed into a novel anti-tuberculosis drug.

This invention provides a monoclonal antibody 4D5 against Rv0340 that can improve drug resistance in Mycobacterium tuberculosis. The heavy chain variable region of antibody 4D5 has the following amino acid sequences: CDR-H1 (SEQ ID No. 1), CDR-H2 (SEQ ID No. 2), and CDR-H3 (SEQ ID No. 3); and the light chain variable region of anti-Rv0340 monoclonal antibody 4D5 has the following amino acid sequences: CDR-L1 (SEQ ID No. 4), CDR-L2 (SEQ ID No. 5), and CDR-L3 (SEQ ID No. 6). This anti-Rv0340 monoclonal antibody 4D5 was prepared using Rv0340 protein as an antigen, and the effect of the anti-Rv0340 monoclonal antibody on the in vitro growth of Mtb in the presence of anti-tuberculosis drugs was investigated. The results showed that antibody 4D5 could significantly increase the sensitivity of Mtb to isoniazid; and when antibody 4D5 was used in combination with isoniazid, the survival rate of Mtb decreased by 26.58%. This invention provides a new monoclonal antibody drug for specifically improving the sensitivity of Mtb to isoniazid, and has the prospect of application as a monoclonal antibody drug to improve the drug resistance of Mycobacterium tuberculosis.

This invention discloses a rapid phenotypic drug susceptibility detection method for Mycobacterium tuberculosis infected samples. The method utilizes the incorporation of deuterium into biomolecules synthesized by metabolically active Mycobacterium tuberculosis in a heavy water (D2O) environment, thereby generating C-D characteristic peaks in single-cell Raman spectroscopy. The inhibition of metabolic activity by anti-tuberculosis drugs leads to a decrease in the C-D signal. By calculating the metabolic change rate between drug-treated and untreated samples, the bacterial drug response can be quantified, and susceptibility / resistance determination and MIC value can be established. This invention provides a rapid phenotypic drug susceptibility detection method for Mycobacterium tuberculosis based on single-cell Raman spectroscopy and heavy water labeling technology (Raman-DIP). This method detects the metabolic changes of individual bacteria under the action of anti-tuberculosis drugs to determine drug susceptibility and minimum inhibitory concentration (MIC), enabling a rapid detection process from sample to result.

The invention relates to a thienopyridone compound, application thereof and an antituberculosis drug. The thienopyridone compound disclosed by the invention has a structure as shown in a formula (I), wherein-Ar1-(R1) n is a C6-C10 aromatic ring substituted by n R1 or a 4-10-membered heteroaromatic ring, n is selected from 0, 1, 2, 3 or 4, and n R1 is selected from C1-C6 alkyl, C1-C5 alkoxy, C3-C10 cycloalkyl, halogen, C1-C8 acyl, C1-C6 alkyl substituted by hydroxyl, C1-C6 alkyl substituted by halogen, nitro or cyano; -Ar2-(R2) n is a C6-C10 arylene ring substituted by n R2 or a 4-10-membered heteroaromatic ring, n is selected from 0, 1, 2, 3 or 4, and n R2 is respectively selected from C1-C6 alkyl, C1-C5 alkoxy, C3-C10 cycloalkyl, halogen or nitryl; and R3 is selected from the following groups: H or C1-C8 acyl groups. The thienopyridone compound has a novel mother nucleus structure and excellent anti-tubercle bacillus activity, and has a very strong inhibition effect on the growth of tubercle bacillus.

The present invention relates to a 2-pyridone thiophene compound, its preparation method, use, and anti-tuberculosis drug. The 2-pyridone thiophene compound of the present invention is a compound of formula (I); wherein: R is one of phenyl, substituted phenyl, and thienyl. The 2-pyridone thiophene compound has a new core structure and excellent anti-Mycobacterium tuberculosis (abbreviated as tuberculosis) activity. The preparation method uses 3-amino-4-bromothiophene-2-methyl carboxylate as a raw material, and is prepared through an amidation reaction and a ring-closure reaction. The reaction steps are simple. The 2-pyridone thiophene compound is used as a drug for treating infectious diseases caused by tuberculosis bacteria, and has a strong inhibitory effect on the growth of tuberculosis bacteria.

The invention discloses a micromolecule polypeptide capable of inhibiting intracellular survival of mycobacterium tuberculosis and application of the micromolecule polypeptide, and belongs to the technical field of biology. The amino acid sequence of the micromolecule polypeptide is VLARYASICQ (SEQ ID NO.1), and the micromolecule polypeptide has cell penetrability, can promote glycolysis, and further inhibits the survival of mycobacterium tuberculosis in macrophages and mice. The micromolecule polypeptide can be used for preparing a medicine for resisting mycobacterium tuberculosis infection. The results of the invention can provide new tools and ideas for clinical prevention and treatment of tuberculosis, and especially have broad prospects in the aspects of development, clinical application and the like of anti-tuberculosis drugs. The invention has important application value for obtaining novel antituberculosis drugs.

The present disclosure provides a kit and its application, the kit comprising two sets of amplification primer groups, single base extension primers and processing reagents; the amplification primer groups are used for amplifying Mycobacterium tuberculosis flora identification sites and anti-tuberculosis drug pharmacogenetic polymorphism sites; each pair of primers corresponds to the upstream and downstream regions of a SNP site; the processing reagents include PCR reaction mixture, PCR enzyme mixture, SAP reaction mixture, SAP enzyme mixture, extension reaction mixture and extension enzyme mixture. By designing specific amplification primer groups and single base extension primers, the system and reagents are optimized, and the sensitivity is high. The kit combined with matrix-assisted laser desorption ionization time-of-flight mass spectrometry can complete the detection of all sites, and the detection cost is low and the efficiency is high.

The invention discloses application of amitriptyline and / or derivatives thereof, a mycobacterium tuberculosis inhibitor and a pharmaceutical composition, relates to the technical field of biological medicines, and discloses application of amitriptyline and / or derivatives thereof in preparation of an inhibitor for inhibiting mycobacterium tuberculosis and / or nontuberculous mycobacteria. According to the application disclosed by the invention, research finds that amitriptyline has a human macrophage level anti-tuberculosis effect and amitriptyline has an effect of inhibiting intracellular survival of mycobacterium tuberculosis and / or nontuberculous mycobacterium at a macrophage level for the first time, which indicates that amitriptyline has an application value as a drug for treating multidrug-resistant tuberculosis; the compound can be used as a novel antituberculous drug.

This invention belongs to the field of biomedicine and specifically relates to the use of a combined synergistic pharmaceutical composition for the treatment of mycobacterial infections. Pimozide (PMZ) described in this invention can be used as an active ingredient in a combined anti-Mycobacterium tuberculosis drug, opening up new applications for PMZ. Combining PMZ with anti-tuberculosis drugs (such as bedaquiline (BDQ) and clofazimine (CFZ)) can enhance anti-tuberculosis activity. PMZ's use as a synergist is expected to shorten treatment courses and reduce drug resistance, representing a novel therapeutic strategy. The combination of PMZ (0.5µg / ml) and BDQ reduced the MIC of susceptible Mycobacterium tuberculosis strain H37Rv to BDQ from 0.06µg / ml to 0.0038µg / ml (a 16-fold increase in efficacy). The combination of pimozide (0.5µg / ml) and BDQ reduced the MIC of the Rv0678 mutant to BDQ from 1µg / ml to 0.0313µg / ml (a 32-fold increase in efficacy), which is lower than the MIC of wild-type H37Rv (0.06µg / ml). This reversed BDQ resistance and further enhanced anti-mycobacterial activity. A 1.5µg / ml PMZ combined with 0.03µg / ml BDQ treatment for 14 days completely killed Mycobacterium 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 discloses application of beta 1,4-galactosyltransferase 1 (B4GALT1) in preparation of a medicine for resisting mycobacterium tuberculosis infection and belongs to the technical field of biotechnology. The application first determines that a host functional protein B4GALT1 can improve the serum IgG galactosylation level, promote macrophage phagocytosis and killing of mycobacterium tuberculosis, and reduce the bacterial load. The B4GALT1 can be used as a new potential medicine for resisting tuberculosis infection. The application achievement can provide a new tool and thought for clinical treatment of tuberculosis, especially has a broad prospect in development and clinical application of an anti-tuberculosis medicine and can be directly applied to the scientific research field. The application has important application value for obtaining a new drug target for resisting tuberculosis and screening a new medicine.

The invention relates to the technical field of biological medicine, in particular to application of salvianolic acid in preparation of an anti-tuberculosis drug. The invention provides application of salvianolic acid A or pharmaceutically acceptable salt thereof in preparation of the anti-tuberculosis drug, the molecular formula of the salvianolic acid A is C26H22O10, and the structural formula is shown in formula I. When the salvianolic acid A is applied to preparation of the anti-tuberculosis drug, a brand new material basis is provided for research and development of the anti-tuberculosis drug, damage of the drug to normal tissues of a human body is reduced, and the anti-tuberculosis drug can be applied to preparation of the anti-tuberculosis drug. Toxic and side effects are reduced. From the aspect of action mechanism, the salvianolic acid A has various biological activities such as inflammation resistance, oxidation resistance and immunoregulation, and can inhibit the growth and reproduction of mycobacterium tuberculosis and enhance the immune defense capability of the body to tubercle bacillus through the multi-target synergistic effect, thereby achieving the purpose of treating 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.

The application belongs to the technical field of medicine, and discloses application of genistein in preparation of medicine for resisting Mycobacterium tuberculosis. The application discloses application of genistein or a pharmaceutically acceptable derivative thereof in inhibition of Mycobacterium tuberculosis or preparation of products for resisting Mycobacterium tuberculosis. Experiments show that the MIC of genistein to M. tb H37Rv ΔleuΔpan and M. tb M. tb M. tb M. tb M. tb H37Ra is 0.03 mg / mL, and under the action of 30 μg / mL genistein, the minimum inhibitory concentration of a rifampicin-resistant strain is reduced from 50 μg / mL to 6.25 μg / mL, which greatly improves the sensitivity of the drug-resistant strain to rifampicin. Therefore, genistein can be used in preparation of medicine for resisting Mycobacterium tuberculosis or resisting tuberculosis alone, and can also be used as an auxiliary medicine for other anti-tuberculosis medicines for combined use, that is, the types of anti-tuberculosis medicines are widened and the course of treatment of tuberculosis is expected to be shortened.

The invention belongs to the technical field of organic synthetic chemistry, and particularly relates to a method for preparing a 1, 3-dithio indolizine compound without a catalyst and application of the 1, 3-dithio indolizine compound. In an organic solvent, substituted 2-methylpyridine, alpha-bromoketone and N-thiosuccinimide are used as raw materials, and a reflux stirring reaction is performed to obtain the 1, 3-dithio indolizine compound. The method does not need to use a metal catalyst and a chemical oxidant, is mild in reaction condition, conforms to the green chemistry principle, and has the characteristics of simplicity and convenience in operation, high yield, good functional group compatibility and the like. Meanwhile, a cell experiment result shows that the 1, 3-dithio indolizine compound provided by the invention has relatively good inhibitory activity on standard strains, sensitive strains and drug-resistant strains of mycobacterium tuberculosis, so that a drug lead compound and a drug candidate are provided for development of a novel anti-tuberculosis drug, and the 1, 3-dithio indolizine compound has a broad application prospect. The important significance is realized on the prevention and / or treatment of tuberculosis.

The invention relates to the technical field of biology, in particular to a fusion protein, mRNA for coding the fusion protein and application of the fusion protein to inhibition of mycobacterium tuberculosis. The invention provides a fusion protein based on an antibacterial peptide combination and bacteriophage pigtail fiber protein or lysin and mRNA for coding the fusion protein, the mRNA can effectively express the antibacterial peptide and the bacteriophage pigtail fiber protein / lysin in macrophages, and after being infected with mycobacterium tuberculosis, the mRNA can effectively express the antibacterial peptide and the bacteriophage pigtail fiber protein / lysin. The antibacterial peptide combination carried by the phage pigtail fiber protein / lysin expressed in the cells specifically targets and kills the mycobacterium tuberculosis, so that the aim of removing the mycobacterium tuberculosis in the cells is fulfilled. Compared with the existing antituberculous drugs, the mRNA preparation disclosed by the invention can be massively expressed in cells, the expression duration is long, and mycobacterium tuberculosis of the cells can be effectively eliminated.

The invention relates to the technical field of microbial fermentation and biological medicine, in particular to a halogenated cyclopentenone compound as well as a preparation method and application thereof. The invention provides a halogenated cyclopentenone compound, which is obtained by carrying out fermentation culture, extraction and separation on mangrove forest plant artemisinin endophytic fungi Perconia macrospinosa F35, and the chemical structure of the halogenated cyclopentenone compound is identified by modern spectrum technologies such as nuclear magnetic resonance, high-resolution mass spectrum, ultraviolet spectrum and the like. Activity research shows that the series of halogenated cyclopentenone can effectively inhibit the activity of key virulence factor tyrosine phosphatase MptpA and MptpB of mycobacterium tuberculosis, shows good anti-tuberculosis activity by inhibiting pathogenic signal channels of pathogenic bacteria, and has wide application potential and development value in the field of anti-tuberculosis drugs.

The invention relates to the technical field of biological medicine manufacturing, and discloses application of an HSPA5 monoclonal antibody in preparation of medicines for blocking tubercle bacillus transmission and / or resisting tuberculosis. The monoclonal antibody is adopted to antagonize the function of HSPA5 protein in a mouse body in a targeted manner, so that precise intervention on HSPA5 positive large vesicles secreted after neutrophil infection is realized, and the problems of survival and replication of mycobacterium tuberculosis in cells and subsequent intercellular, intertissue and individual propagation are solved.

The invention belongs to the technical field of biological medicines, and particularly discloses application of indolinone compounds in preparation of anti-mycobacterium tuberculosis medicines. The molecular structural formula of the indolinone compound is shown as a formula (A), and the indolinone compound has the advantages of high inhibitory activity, high selectivity, low toxicity and the like as a PafA inhibitor, can be used for developing novel antituberculosis drugs and overcomes the problem of severe drug resistance of drugs for clinically treating tuberculosis.

The invention relates to the technical field of biological medicine manufacturing, and discloses application of an HSPA5 monoclonal antibody in preparation of medicines for blocking tubercle bacillus transmission and / or resisting tuberculosis. The monoclonal antibody is adopted to antagonize the function of HSPA5 protein in a mouse body in a targeted manner, so that precise intervention on HSPA5 positive large vesicles secreted after neutrophil infection is realized, and the problems of survival and replication of mycobacterium tuberculosis in cells and subsequent intercellular, intertissue and individual propagation are solved.

The present invention discloses the use of acivicin in preparing anti-mycobacterium tuberculosis drugs, belonging to the technical field of biomedicine. The present invention discloses the use of acivicin in preparing anti-mycobacterium tuberculosis and anti-tuberculosis drugs, and the present invention confirms through in vitro experiments that acivicin has a good effect of inhibiting Mtb H37Rv and Mtb H37Ra. Therefore, acivicin can be used to prepare anti-mycobacterium tuberculosis or anti-tuberculosis drugs alone, and can also be used as an auxiliary drug for combined use with other anti-tuberculosis drugs. That is, the present invention broadens the types of anti-tuberculosis drugs and is expected to shorten the treatment course of tuberculosis. At the same time, the present invention belongs to "new uses of old drugs", thus saving drug research and development costs and treatment costs, and has obvious economic benefits and clinical application value.

The invention belongs to the field of biological medicine, and particularly relates to application of murrayone or a pharmaceutically acceptable carrier or excipient thereof in preparation of a medicine for preventing and / or treating mycobacterium tuberculosis infection. In-vitro experiments show that murrayone has specific and efficient inhibiting and killing effects on mycobacterium tuberculosis, and has no activity on common gram-positive and gram-negative bacteria. When the murrayone is combined with first-line antituberculosis drugs (such as isoniazide and rifampicin), the drug effects are added. A time killing curve proves that the mycobacterium tuberculosis with high bacterial loading capacity can be completely removed within 48 hours, and the sterilizing effect is lasting. Cell experiments show that the compound has low toxicity to THP-1 human macrophages and good safety, and can effectively kill intracellular infected mycobacterium tuberculosis clinical strains. Therefore, the murrayone can be used as a single drug component or a drug combination component, is used for developing novel, efficient and safe antituberculosis drugs, and is particularly suitable for treating infectious diseases caused by mycobacterium tuberculosis.

A composition comprising a hypoxia-inducible factor prolyl hydroxylase inhibitor and an antituberculosis drug, and a use thereof in the preparation of medicines or health care products for preventing and treating chronic inflammatory anemia and infections. The obtained medicines or health care products can alleviate chronic inflammatory anemia caused by interference from mycobacterium tuberculosis, and can be used for treating tuberculosis.

The invention provides an anti-drug-resistant mycobacterium tuberculosis cinnamon extract I and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine extracts.Cinnamon is used as a raw material, and the cinnamon extract I with the anti-drug-resistant mycobacterium tuberculosis effect is obtained through moving bed extraction, countercurrent chromatography separation and distillation. The cinnamon extract I disclosed by the invention has obvious anti-mycobacterium tuberculosis activity, and has a good inhibition effect on mycobacterium tuberculosis and various drug-resistant mycobacterium tuberculosis; the cinnamon extract I has no synergistic effect with common anti-tuberculosis drugs such as rifampicin, isoniazide, ethambutol, streptomycin and levofloxacin, and has no cross resistance with rifampicin, isoniazide and levofloxacin, so that the cinnamon extract I possibly has a unique antibacterial mechanism for mycobacterium tuberculosis, and a new thought and a new method can be provided for prevention and treatment of tuberculosis.

This invention discloses a plant pta The study of gene-inactivated BCG mutant strains and their applications falls under the fields of biotechnology and infectious disease prevention and control. Mutant strain B494 (accession number CCTCC NO.M 20253064) was obtained through screening a random insertion mutant library of Mycobacterium bovis BCG. Identification revealed that the mutation occurred in... pta The gene (SEQ ID NO.1), inactivation of which leads to impaired bacterial energy metabolism, intracellular acidification, decreased tolerance to environmental stress, and reduced survival and proliferation capacity within macrophages. This invention discloses... pta Genes play a central role in regulating mycobacterial metabolism and virulence. The mutant strain B494 exhibits significant attenuated characteristics and can serve as a candidate strain for novel attenuated live tuberculosis vaccines or for screening anti-tuberculosis drugs that regulate metabolism.

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.