159 results about "Anti tubercular" patented technology

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 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 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 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.

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 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 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.

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.

The invention relates to the technical field of biology, in particular to a protective monoclonal antibody targeting Mycobacterium tuberculosis PspA and a preparation method and application thereof, the protective monoclonal antibody comprises at least one of the following CDR sequences or a sequence with one amino acid substituted, deleted or increased: a heavy chain variable region CDR sequence: SEQ ID NO: 4-6; the light chain variable region CDR sequences are as shown in SEQ ID NO: 8-9 and WAS. The antibody or the antigen binding fragment can specifically bind to PspA protein of mycobacterium tuberculosis (MTB), shows efficient antituberculous activity in vivo and in vitro, specifically, can significantly enhance phagocytosis of macrophages on tubercle bacillus, inhibit tubercle bacillus growth and the like, and is clear in sequence and structure, so that the antibody or the antigen binding fragment is easy to develop and transform, and has broad application prospects. And moreover, an immune-mediated treatment mechanism is not easy to induce pathogens to generate drug resistance, so that when being applied to prevention and treatment of tuberculosis, not only is a new choice provided for treatment of tuberculosis, but also an important basis is provided for response of drug-resistant strains, development of diagnostic reagents, vaccine development and the like, and the application prospect is wide.

The present invention discloses the use of an inhibitor targeting T-cell TIGIT in the preparation of an anti-tuberculosis drug. The inhibitor includes ociperlimab, AGEN1777, tiragolumab, etc. The present invention blocks TIGIT on the surface of T cells, promoting the ability of T cells to clear intracellular bacteria in macrophages by upregulating MPEG1, thereby achieving control of tuberculosis proliferation and providing evidence for the development of anti-tuberculosis drugs.

The invention provides a method for predicting the dosage of an antituberculous drug, which comprises the following steps of: establishing a group pharmacokinetic model of the antituberculous drug by adopting a nonlinear mixed effect model, a two-atrioventricular model and a mixed residual model through plasma concentration analysis, and calculating the pharmacokinetic parameters of the corresponding model; and the established model is verified based on a graphical method, a visual prediction test method and a nonparametric bootstrap method, and the steps of stability and prediction capability evaluation and the like are completed. According to the anti-tuberculosis drug population pharmacokinetic model established by the invention, individual pharmacokinetic parameters can be estimated, a specific population administration scheme is optimized, the drug curative effect is improved, the adverse reaction risk is reduced, and individualized administration of the anti-tuberculosis drug is realized.

The invention belongs to the technical field of medicines, and particularly relates to a nitroimidazole oxazole derivative as well as a preparation method and application thereof. The invention provides a nitroimidazo oxazole derivative as shown in a formula I. The nitroimidazo oxazole derivative shows better in-vivo and in-vitro anti-tuberculosis activity, has good solubility and bioavailability, can be used for treating diseases caused by mycobacterium tuberculosis infection, and is particularly suitable for diseases caused by drug-resistant mycobacterium tuberculosis.

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.

The invention discloses application of valerian in preparation of a medicine for resisting mycobacterium tuberculosis, and relates to the technical field of bioengineering. The molecular formula of the valerianin disclosed by the invention is C22H30O8. The mycobacterium tuberculosis is a mycobacterium tuberculosis H37Rv strain. The invention discloses valerian as a natural-source compound for the first time, the valerian has the dual advantages of high efficiency and low toxicity, the valerian has an obvious effect of resisting mycobacterium tuberculosis, a brand new candidate drug scheme with development potential is provided for solving the difficulty of tuberculosis treatment, and the valerian has great scientific value and application prospect.

The invention discloses a common rabdosia leaf above-ground whole herb water extraction extract and application thereof, the above-ground whole herb part of common rabdosia leaves is taken, the obtained extract is characterized by being a whole herb water extraction total extract, petroleum ether and ethyl acetate are respectively and sequentially used for extraction, and the respective extracted parts are separated. The isodon amethystoides herb extract disclosed by the invention has an effect of resisting mycobacteria, which is expressed by inhibiting the growth activity of mycobacteria, including mycobacterium tuberculosis. The isodon amethystoides herb extract disclosed by the invention can be used for preparing a medicine for resisting mycobacterium tuberculosis.

The invention discloses application of botrychium ternatum total extract and petroleum ether layer extract in antituberculous activity and a preparation method of the botrychium ternatum total extract and the petroleum ether layer extract, and tests prove that the botrychium ternatum total extract and the petroleum ether layer extract show remarkable antituberculous activity and particularly have a specific inhibition effect on multidrug-resistant strains (such as Mtb706). It is prompted that the compound can possibly become a potential alternative drug source for multi-drug resistant tuberculosis (MDR-TB). Meanwhile, active substances of the petroleum ether layer extract provide a clear direction for subsequent separation and identification, and the screening range of the antituberculous active ingredients in the botrychium ternatum is effectively narrowed. And a methodological foundation is laid for extraction process optimization and active component targeting research of the botrychium ternatum antituberculous drug.

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.

The present application relates to a kind of mycobacterium tuberculosis protective antigen combination and its application, specifically, the antigen of the application is combination antigen, at least includes the following antigen: Ag85B, Rv2465c, Rv2029c, Rv3406;The application is the vaccine for resisting mycobacterium tuberculosis.

The invention belongs to the technical field of medicines, and discloses a prodrug of a pyrrole-2-formamide compound, a preparation method of the prodrug, a pharmaceutical composition taking the compound as an active component, and application of the prodrug in preparation of medicines for preventing or treating MmpL3 target related diseases. Specifically, the invention relates to a compound shown in a formula (I) or pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound, a use method thereof and a method for preparing the compounds, and X and R are described in the specification.

The application provides a milk exosome coated PLGA nanometer anti-tuberculosis drug system and preparation and application. The system structure is: anti-tuberculosis drug-milk exosome@PLGA-anti-tuberculosis drug. The anti-tuberculosis drug is selected from a combination of one or more of aminoquinolones, benzothiazoles, arylquinolines, nitrobenzamide and benzothiazinone anti-tuberculosis drugs. The nanometer anti-tuberculosis drug system prolongs the circulation time of nanoparticles in blood, improves the bioavailability of the drug, enhances the cell uptake efficiency of nanoparticles, improves the drug delivery effect, reduces the immune rejection reaction and potential toxicity, and improves the safety of treatment.