285 results about "Anti tubercular" patented technology

The invention discloses an application of an inhibitor aiming at T cell TIGIT in preparation of an anti-tuberculosis drug. The inhibitor comprises an Ociperlimab (Ociperlimab), an AGEN1777 (AGEN1777), a Tiragolumab (Tiragolumab) and the like. The TIGIT on the surface of the T cell is blocked, the T cell is promoted to increase the capacity of eliminating intracellular bacteria of macrophages by up-regulating MPEG1, the proliferation of tubercle bacillus is controlled, and evidence is provided for developing antituberculous drugs.

The invention discloses an application of cryptotanshinone in preparation of an anti-mycobacterium tuberculosis drug, and relates to the technical field of bioengineering. The molecular formula of the valerianin disclosed by the invention is C19H20O3. The mycobacterium tuberculosis is a mycobacterium tuberculosis H37Rv strain. Cryptotanshinone is disclosed as a natural-source compound for the first time, has the dual advantages of high efficiency and low toxicity, has an obvious effect of resisting mycobacterium tuberculosis, provides a brand new candidate drug scheme with development potential for solving the difficulty of tuberculosis treatment, and has great scientific value and application prospect.

The present invention provides novel pyridine carboxamide compounds that have anti-tubercular activity. The compounds of the invention have inhibitory action against drug sensitive as well as drug resistant M. tuberculosis infection.

The invention discloses a primer composition and application thereof. According to the invention, a group of primer compositions is obtained aiming at mycobacterium tuberculosis complex group identification and drug resistance related genes thereof. The primer composition can be combined with nucleic acid matrix-assisted laser desorption ionization time-of-flight mass spectrometry to detect a mycobacterium tuberculosis complex group, and can also detect the mutation conditions of 18 drug-resistant genes and 92 gene mutations related to drug resistance of 21 common first-line and second-line antituberculous drugs / types in the mycobacterium tuberculosis complex group. The medication is guided. Based on a MassARRAY technical platform, the primer composition has the advantages of good accuracy, high sensitivity, short required time and high efficiency when being used for detecting the mycobacterium tuberculosis complex group and the drug resistance thereof, is suitable for various sample types, can meet clinical detection requirements, is beneficial to clinical diagnosis and medication guidance of mycobacterium tuberculosis, and realizes precise treatment of pulmonary tuberculosis.

The invention provides application of B-AP15 in preparation of antituberculosis drugs, and particularly belongs to the technical field of drug preparation. The B-AP15 is used for preparing the antituberculous drugs and has relatively good inhibitory activity on MTB standard strains, MTB sensitive strains and clinical drug-resistant strains, so that a drug lead compound and a drug candidate are provided for development of the novel antituberculous drugs, and the B-AP15 has important significance on prevention and / or treatment of tuberculosis.

The invention relates to a method for detecting six second-line antituberculous drugs by high performance liquid chromatography. The method comprises the following steps: providing an internal standard stock solution and a standard stock solution of six second-line antituberculosis drugs; preparing an internal standard working solution and a standard curve working solution by utilizing the diluent; preparing a solution of a product to be detected by using the Tianlongitudinal sample extraction liquid TZ-002; a liquid chromatograph is used for detection, and the conditions are as follows: a mobile phase A is a Tianlongitudinal sample releasing agent TZ-D004; a mobile phase B is acetonitrile; a mobile phase C is water; and gradient elution. According to the method, the plasma concentration of the second-line antituberculous drug taken by a tuberculosis patient is measured by applying the reversed-phase high-performance liquid chromatography, the cost is relatively low, the analysis time is short, the sensitivity is high, and the accuracy is high. The kit can be used for simultaneously detecting the blood concentration of six second-line antituberculosis drugs such as isopropylthioamide, levofloxacin, linezolid, moxifloxacin, deramanib and bedaquiline in human serum, and is expected to provide a more reliable basis for clinicians to adjust the dosage of the antituberculosis drugs.

The invention relates to novel rufomycin analogs targeting C1pC1 protease. The compounds of the invention have antibacterial activity, for example, with anti-tuberculosis properties, and are useful for the treatment of, for example, tuberculosis.

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 discloses application of Rv2610 in preparation of a medicine for resisting mycobacterium tuberculosis infection, and belongs to the technical field of biology. The invention finds that the Rv2610 can promote the adhesion capacity of mycobacterium tuberculosis to macrophages and inhibit the expression of early inflammatory molecules TNF-alpha and IL-1beta of the macrophages, and in a mouse infection model, the Rv2610 promotes the colonization of mycobacterium in the lung in vivo. The Rv2610 can be used as a new drug target for resisting tuberculosis infection, and an inhibitor of the Rv2610 can be used for preparing a drug for resisting mycobacterium tuberculosis infection. The invention provides new tools and ideas for clinical prevention and treatment of tuberculosis, particularly has wide prospects in the aspects of development, clinical application and the like of antituberculosis drugs and vaccines, and can also be applied to the field of scientific research or guide development of inhibitors for inhibiting mycobacterium tuberculosis from infecting host macrophages. The invention has important application value for obtaining new anti-tuberculosis drug targets and screening new drugs.

This invention concerns pharmaceutical compositions for administration via intramuscular or subcutaneous injection, comprising micro- or nanoparticles of the anti-TB compound bedaquiline, suspended in an aqueous pharmaceutically acceptable carrier, and the use of such pharmaceutical compositions in the treatment and prophylaxis of a pathogenic mycobacterial infection.

The invention discloses a BCG1059c gene knock-down recombinant bacillus calmette guerin vaccine strain, and the BCG1059c gene of the strain is knocked down. A CRISPRi / dCas9th1 technology is utilized to block RNA polymerase movement in space through a compound formed by crRNA, dCas9 protein and sgRNA at a transcriptional level, so that the expression of the BCG1059c gene in the BCG vaccine is inhibited. The strain has the characteristics of low-abundance polar fat and high-abundance fat arabinomannan compared with wild BCG (Bacillus Calmette Guerin); in an in-vitro experiment, compared with a wild type BCG, the macrophage treated by the BCGkd can secrete IL-2 and TNF-alpha at a higher level, and shows a stronger bactericidal ability on escherichia coli; in an in-vivo experiment, after intravenous injection of a mouse, the survival time of the gene knock-down strain BCGkd in the lung can reach more than 16 weeks, and a more lasting anti-tuberculosis capability can be provided.

The invention relates to an application of bisphenicol in preparation of a product for inhibiting mycobacterium tuberculosis, the bisphenicol has a very good antibacterial effect on mycobacterium tuberculosis, the MIC of the bisphenicol on a mycobacterium tuberculosis standard strain (ATCC25618) is 0.125 mu g / mL, and the MBC of the bisphenicol on the mycobacterium tuberculosis standard strain is 0.25 mu g / mL. The bisphenicol has low cytotoxicity and good safety, and can be used as a candidate drug to be applied to the development of anti-mycobacterium tuberculosis infection drugs.

The invention relates to a 6, 5, 7, 6-tetracyclic derivative with a structural characteristic shown in a formula (I) as well as a preparation method and application of the 6, 5, 7, 6-tetracyclic derivative, including application of pharmaceutically acceptable salt of the 6, 5, 7, 6-tetracyclic derivative in treatment of tuberculosis. The compound is novel in structure, has good in-vitro and in-vivo anti-tubercle bacillus activity, and is a novel anti-tubercle bacillus compound with a good application prospect in the field of medicines. # imgabs0 #

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 purpose of this invention is to provide a polypeptide with anti-tuberculosis activity, its preparation method, and its application, belonging to the field of biotechnology. The preparation method of the polypeptide of this invention includes the following steps: (1) preparing a linear polypeptide, the sequence of which is shown in SEQ ID NO:1; (2) subjecting the thiol groups of two cysteine ​​residues in the linear polypeptide to a dehydration condensation reaction with 1,3-dihydroxymethylurea to obtain the polypeptide. The polypeptide of this invention has low cytotoxicity and good anti-tuberculosis effect.

The application belongs to the technical field of biological medicine, and particularly relates to a non-classical IFN-gamma-dependent mycobacterium tuberculosis peptide epitope P15, a coding sequence and application thereof, and an anti-tuberculosis vaccine. The amino acid sequence of the mycobacterium tuberculosis peptide epitope P15 is shown as SEQ ID NO. 1. The application is found through research that the mycobacterium tuberculosis peptide epitope P15 has good immunogenicity, in-vivo immunity has a significant anti-tuberculosis protection effect, and the protection effect is not dependent on the host cell IFN-gamma response, and can be used as an ideal target antigen of a tuberculosis vaccine, and is made into an epitope vaccine, and has a good application prospect.

The present invention relates to novel primers and sloppy molecular beacon and molecular beacon probes for amplifying segments from different genes in Mycobacterium tuberculosis for identifying the presence of M.tb DNA and / or resistance to anti-tuberculosis drugs.

FIELD: pharmacology.SUBSTANCE invention can be used to determine the concentration of an anti-tuberculosis drug in blood serum. The method for determining the concentration of bedaquiline in the blood serum in patients with tuberculosis or mycobacteriosis is that whole blood samples are centrifuged at 3000 rpm for 20 minutes, then the blood plasma is collected in sterile 1.5 mL Eppendorf tubes, then 900 mcL of acetonitrile are added to 300 mcL of plasma and centrifuged at 13500g for 15 minutes, then 1 mL of the supernatant is transferred to a chromatographic vial and make the assay by UHPLC MS / MS using an Athena UHPLC C18, 1.8 mcM, 120A, 2.1×100 mm chromatography column, when using an aqueous solution containing 5 g / L of ammonium acetate, 25 ml / L of concentrated acetic acid, 2 ml / L trifluoroacetic acid as mobile phase A and 100% acetonitrile as mobile phase B, the concentration of bedaquiline is determined using a pre-plotted calibration curve.EFFECT: determination of bedaquiline in human blood plasma in a time not exceeding 6 minutes.1 cl, 9 dwg, 6 tbl

There is an urgent need for an effective therapeutic vaccine against tuberculosis (TB), which remains a major public health problem. Current "classical" strategies under development have failed or are suboptimal, and more effective vaccines are needed to achieve the World Health Organization's 2035 End TB Strategy. We have generated a post-exposure / therapeutic TB vaccine candidate (CD40.TB) whose heavy chain consists of an antibody directed against a surface antigen (i.e., CD40) of antigen-presenting cells (i.e., dendritic cells) conjugated to three relevant Mycobacterium tuberculosis (Mtb) antigens and which is liable to induce potent anti-TB humoral and cellular immunity.

According to the invention, 23 key miRNAs are identified in patients with liver injury caused by taking antituberculous drugs. Compared with patients who cannot cause liver injury by taking antituberculous drugs, the miRNAs are obviously differentially expressed in the patients who cannot cause liver injury by taking antituberculous drugs. Furthermore, five miRNAs are selected from the key miRNAs to construct a diagnosis model for drug-induced liver injury caused by tuberculosis and antituberculosis drugs. The model can accurately diagnose tuberculosis, and also can accurately diagnose drug-induced liver injury caused by antituberculosis drugs.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting BCG (bacillus calmette guerin) BCG3965 as well as a preparation method and application of the protective monoclonal antibody. The antibody or an antigen binding fragment comprises a CDR sequence selected from at least one of the following sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 3-5; and the light chain variable region CDR sequences are as shown in SEQ ID NO: 7-9. The monoclonal antibody 5F10 shows efficient antituberculous activity in vivo and in vitro through specific targeting of BCG3965 protein on the surface of mycobacterium tuberculosis, mainly including the aspects of remarkably enhancing the phagocytosis of macrophages on tubercle bacillus, inhibiting tubercle bacillus growth and the like, and in addition, the monoclonal antibody 5F10 is clear in sequence and structure, easy to develop and modify, and capable of being used for preparing antituberculous drugs for treating mycobacterium tuberculosis. The monoclonal antibody 5F10 disclosed by the invention has the advantages that the monoclonal antibody 5F10 is not easy to induce pathogens to generate drug resistance by an immune-mediated treatment mechanism, and the monoclonal antibody 5F10 is applied to prevention and treatment of tuberculosis, not only provides a new choice for treatment of tuberculosis, but also provides an important technical basis for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and is wide in application prospect.

The present invention relates to novel synthetic lipidic alkynylcarbinols, in particular as antibacterial agents, preferably against mycobacteria, and more preferably against species from the Mycobacterium tuberculosis complex, and also to therapeutic uses thereof. The present invention also relates to said compounds for use for the treatment of bacterial infections. The present invention further relates to the discovery of the pharmaceutical mechanism and bioactivity of these novel synthetic lipidic alkynylcarbinols.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting mycobacterium tuberculosis MPT83 as well as a preparation method and application of the protective monoclonal antibody. The antibody or an antigen binding fragment comprises a CDR sequence selected from at least one of the following sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 5-7; cDR sequences of a light chain variable region are as follows: SEQ ID NO: 9-10 and LAS. The monoclonal antibody 9C9 can be specifically combined with MPT83 protein on the surface of Mycobacterium tuberculosis (MTB) and shows efficient antituberculous activity in vivo and in vitro, the activity mainly comprises the aspects of remarkably enhancing the phagocytosis of macrophages on tubercle bacillus, inhibiting tubercle bacillus growth and the like, and in addition, the monoclonal antibody 9C9 is clear in sequence and structure, easy to develop and modify and capable of being used for preparing the anti-tubercle bacillus monoclonal antibody 9C9. The monoclonal antibody 9C9 disclosed by the invention has the advantages that the monoclonal antibody 9C9 can be used for preventing and treating tuberculosis, an immune-mediated treatment mechanism of the monoclonal antibody 9C9 does not easily induce pathogens to generate drug resistance, a new choice is provided for the treatment of tuberculosis when the monoclonal antibody 9C9 is applied to prevention and treatment of tuberculosis, an important technical basis is also provided for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and the application prospect is wide.

The invention provides application of bacteroides fragilis 839 in preparation of health food, food composition or medicine for improving hepatotoxicity caused by antituberculosis medicine. The bacteroides fragilis BF839 is adopted for the first time in the world to improve the mouse hepatotoxicity caused by the antituberculous drug, and it is found that the bacteroides fragilis BF839 can reduce or relieve the mouse hepatotoxicity caused by the antituberculous drug and has the advantages of being efficient and safe.

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 belongs to the field of medical technology, discloses substituted pyrrole-2,5-dione compounds and preparation methods and uses thereof, relates to pharmaceutical compositions in which the compounds are active ingredients, and their applications in treating and / or preventing infectious diseases caused by Mycobacterium tuberculosis. Specifically, the present invention relates to a compound shown in formula (I), a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the compound of the present invention, wherein R1, R2, and R3 are as described in the specification. The present invention aims to prepare a new compound having anti-mycobacterium tuberculosis activity, which, as a potential new drug, can be used for infectious diseases caused by bacteria, particularly for the treatment or preventive treatment of pulmonary tuberculosis (TB) diseases caused by Mycobacterium tuberculosis.

The present invention discloses a compound with structural formula I. The compound of the present invention exhibits strong inhibitory activity against Mycobacterium tuberculosis, has good antituberculosis effects, and has a significantly reduced MIC value compared with isoniazid, a first-line clinical drug. It has weak inhibitory effects on the proliferation of human hepatoma cells HepG2 and Chang cells and has good safety. In addition, in the experiment of Mycobacterium tuberculosis infection overexpressing DprE1, the antibacterial ability of the compound decreased, further verifying that the compound exerts its antibacterial effect by inhibiting the DprE1 enzyme, and it is a novel DprE1 inhibitor.

The invention discloses a recombinant rMS:: MPT64 and an application thereof. The recombinant rMS:: MPT64 is prepared by transfecting mycobacterium smegmatis by a recombinant vector for expressing an MPT64 gene. According to the present invention, the MPT64 gene is integrated into Mycobacterium smegmatis (MS) to construct the recombinant MS (rMS:: MPT64) for expressing the MPT64, and the recombinant MS (rMS:: MPT64) has excellent immunogenicity and excellent anti-tuberculosis effect when being used in the tuberculosis vaccine.

The invention belongs to the technical field of biological medicines, and particularly relates to a group of synergists for anti-tuberculosis infection medicines and application of the synergists. In the invention, Vortioxetine (Vor) shows obvious activity for enhancing mycobacterium infection resistance: under the concentration of 2 mu g / mL, the MIC (minimal inhibitory concentration) of Bedaquiline to H37Rv can be reduced by about 64 times (from 0.06 mu g / mL to 0.0009375 mu g / mL), and the MIC of Bedaquiline to an Rv0678 mutant strain can be reduced by about 64 times (from 1 mu g / mL to 0.0156 mu g / mL). And the content of sertraline hydrochloride (STL) can be reduced by about 16 times and 8 times respectively. The synergistic effect of fluoxetine (FXT) is weakest and is only reduced by two times. The synergist disclosed by the invention is a drug which has been sold on the market, so that the synergist has safety and complete medication guidance. The preparation process and the production process are both perfect, the product can be quickly sold on the market, the selling price is reasonable, the market acceptability is good, and the patient compliance is high. The votioxetine or the sertraline can be used as a synergist of a medicine for resisting mycobacterium tuberculosis infection.

This application relates to the field of biomedical technology, and in particular to the application of a small molecule D6 and its derivatives in the preparation of anti-tuberculosis drugs. Through research, this application has discovered that small molecule D6 can specifically target methionine synthase in Mycobacterium tuberculosis to block the methionine synthesis pathway, thereby causing metabolic disorders and cell death in the bacteria. Furthermore, this small molecule D6 exhibits significant antibacterial activity against various Mycobacterium tuberculosis strains, including drug-resistant and dormant strains. Therefore, this small molecule D6 can be well-suited for the preparation of anti-tuberculosis drugs.