29 results about "Antituberculosis drug" patented technology

The invention belongs to the technical field of medical equipment, and particularly relates to a portable tuberculosis drug aerosol inhalation device. The device comprises a medicine storage chamber, an outflow channel and a controller, the top of the medicine storage chamber is provided with a medicine tank groove with a conical pricking pipe, and one-step medicine filling through placing and pressing can be achieved; the respiratory rhythm of a user is identified through lip contact and a respiratory airflow sensor, and the atomizer is synchronously controlled to start and stop; the system has the functions of liquid medicine identity recognition, heating temperature control and self-adaptive power adjustment based on liquid medicine storage, efficient, safe and comfortable tuberculosis medicine inhalation treatment is achieved, and the medication compliance and the treatment effect are remarkably improved.

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 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.

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

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 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.

The invention provides an establishment method of an antituberculous drug-induced liver injury prediction model and a prediction system thereof, and belongs to the technical field of biomedicine. Aiming at the influence of multiple factors on antituberculosis drug-induced liver injury (ADLI), the prediction effects of different types of variables are integrated by utilizing a machine learning method, meaningful potential prediction variables are obtained after screening, the method is not limited to existing possible indexes, meanwhile, new potential variables can be found, and the method has a good application prospect. The occurrence of the anti-tuberculosis drug-induced liver injury can be accurately predicted. Therefore, the ADLI occurrence risk of a pulmonary tuberculosis patient is evaluated through a machine learning method before the antituberculosis drug is applied, that is, the ADLI occurrence risk of different patients can be preliminarily known before treatment by utilizing the antituberculosis drug-induced liver injury prediction model established by the invention, and information is provided for personalized treatment of the patients.

The invention provides a milk exosome coated PLGA (poly (lactic-co-glycolic acid)) nano antituberculosis drug system as well as preparation and application thereof. The structure of the system is as follows: anti-tuberculosis drug-milk exosome-coated PLGA-anti-tuberculosis drug. The antituberculous drug is selected from one or a combination of more of aminoquinolones, benzothiazoles, aryl quinoline, nitrobenzamides and benzothiazinone antituberculous drugs. According to the nano antituberculosis drug system, the circulation time of nano particles in blood is prolonged, and the bioavailability of the drug is improved. The cellular uptake efficiency of the nanoparticles is enhanced, and the drug delivery effect is improved. The immunological rejection and the potential toxicity are reduced, and the treatment safety is improved.

The invention discloses a 2-[2-(thiophenyl) benzothiazole-6-yl] acetamide compound with antimicrobial activity and / or pharmaceutically acceptable salt and application thereof, and relates to the technical field of chemical and pesticide chemical development. The 2-[2-(thiophenyl) benzothiazole-6-yl] acetamide compound with antimicrobial activity and / or the pharmaceutically acceptable salt thereof provided by the invention are / is obtained by carrying out structure optimization on the basis of benzothiazole active compounds in black ants. The compound provided by the invention has a certain inhibition effect on plant pathogenic fungi and animal pathogenic bacteria, and realizes broad-spectrum antimicrobial activity by inhibiting succinate dehydrogenase (SDH), and an acute toxicity test shows that the compound is good in safety. The 2-[2-(thiophenyl) benzothiazole-6-yl] acetamide compound with antimicrobial activity and / or the pharmaceutically acceptable salt thereof provided by the invention can be prepared into a bactericidal pesticide, and can also be used as a structure precursor of an antituberculosis drug.

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 application discloses a glycosylation modified polyethylene imine and application thereof as an anti-tuberculosis drug. The glycosylation modified polyethylene imine provided by the application is obtained by reacting polyethylene imine with gluconolactone, and one or more amino groups on the polyethylene imine are modified with a gluconolactone group L (HOCH2(CHOH)4CO-). Further, the anti-tuberculosis activity, cytotoxicity and stability of the glycosylation modified polyethylene imine are verified through a series of experiments, and the experimental results show that the toxicity of the gluconolactone modified polyethylene imine to normal cells is obviously reduced, the polyethylene imine has high inhibitory activity to tubercle bacillus, and the polyethylene imine has good stability, so the polyethylene imine has great clinical application potential as a new anti-tuberculosis drug.

The invention relates to the technical field of medical consumables, in particular to a finished product of a 3D-printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone as well as a preparation method and application of the finished product of the 3D-printed PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone. The finished product of the 3D printing PaMZ / PLGA-loaded hydroxyapatite / calcium silicate ceramic artificial bone comprises a hydroxyapatite / calcium silicate ceramic artificial bone and a PaMZ / PLGA slow-release system, and can effectively and slowly release antituberculosis drugs for sterilization for a long time, so that spinal tuberculosis is thoroughly treated. The drug-loaded artificial bone material disclosed by the invention can be applied to filling of bone defect parts of spinal tuberculosis, so that the practical problem that hydroxyapatite ceramic artificial bones are relatively low in strength is solved, and the problem that the blood concentration of the bone defect parts of spinal tuberculosis is relatively low is also solved, and thus the cure rate of spinal tuberculosis is increased.

The invention relates to a 2-pyridone thiophene compound as well as a preparation method and application thereof and an antituberculosis drug. The 2-pyridone thiophene compound disclosed by the invention is a compound as shown in a formula (I), and in the imgabs0 #, R is one of phenyl, substituted phenyl and thienyl. The 2-pyridone thiophene compound has a novel mother nucleus structure and excellent activity of resisting mycobacterium tuberculosis (mycobacterium tuberculosis for short). According to the preparation method, 3-amino-4-bromothiophene-2-methyl formate is taken as a raw material, the compound is prepared through amidation reaction and ring closing reaction, and the reaction steps are simple. The 1, 2-pyridone thiophene compound can be used as a medicine for treating infectious diseases caused by tubercle bacillus, and has a very strong inhibition effect on the growth of tubercle bacillus.

The invention provides a pharmaceutical composition for preventing and / or treating diseases caused by mycobacterium tuberculosis infection. The pharmaceutical composition contains a substance for inhibiting the activity of Rv2521 protein or a substance for reducing the content of the Rv2521 protein. According to the invention, an Rv2521 large-fragment knockout strain delta Rv2521 is constructed, and a complement strain delta Rv2521:: 2521 is further constructed, compared with cells infected with delta Rv2521, the death rate of the cells infected with the WT or delta Rv2521: 2521 strain is obviously increased, and the intracellular LPO (marker of ferroptosis) level displayed by the cells infected with the WT or delta Rv2521: 2521 strain is obviously higher than that displayed by the cells infected with the delta Rv2521 strain, so that the death rate of the cells infected with the delta Rv2521 strain is obviously increased. The Mtb Rv2521 is a key ferroptosis promoting effector in the mycobacterium tuberculosis infection process, can promote the survival and dissemination of mycobacterium tuberculosis in macrophages, and can provide a new target spot for clinical tuberculosis treatment and antituberculosis drug development.

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 discloses application of phenothiazine compounds in preparation of antituberculosis drugs, and belongs to the technical field of biomedicine. The invention discloses application of phenothiazine compounds in preparation of antituberculous drugs, phenothiazine compounds X79 serve as a photosensitizer to mediate photodynamic therapy to generate active oxygen to achieve host-oriented treatment, a brand new treatment strategy is provided for infection of intracellular bacteria such as mycobacterium tuberculosis, biocompatibility is excellent, functional modification is easy to achieve, and the phenothiazine compounds X79 can be applied to preparation of antituberculous drugs. Good application prospects are realized in the field of tuberculosis treatment.

The invention relates to the field of biotechnology and pharmacy, in particular to a tuberculosis treatment drug target based on a mycobacterium DNA rotary enzyme aggregate, which comprises an aggregate of GyrA and GyrB subunits of mycobacterium DNA rotary enzyme as an active component. According to the invention, a liquid aggregate formed by GyrA and GyrB subunits is used as a new target for tuberculosis treatment, unique physical characteristics of the subunits in an aggregate state are disclosed, a new thought is provided for drug design, the GyrA and GyrB subunits of the mycobacterium DNA rotary enzyme can form the aggregate with liquid characteristics under specific conditions, and the treatment effect of tuberculosis is improved. The GyrA and GyrB subunits of the mycobacterium DNA gyrase have the characteristic of being converted into a solid state or a fiber state, the characteristics of the aggregates enable the GyrA and GyrB subunits to become potential drug targets, new antituberculosis drugs can be developed, bioinformatics and experimental verification show that the GyrA and GyrB subunits of the mycobacterium DNA gyrase have the potential of forming biological aggregates, and the potential of the GyrA and GyrB subunits serving as the drug targets of the GyrA and GyrB subunits of the mycobacterium DNA gyrase are shown.

The invention discloses application of quinone compounds in preparation of antituberculous drugs, and relates to the technical field of biological medicines. According to the invention, an inhibitor targeting a prokaryotic ubiquitin-proteasome degradation system is screened out by constructing a Dop protein inhibitor high-throughput screening technology model, i.e., a quinone compound 2-methoxy-1, 4-naphthoquinone and a derivative 2-bromo-1, 4-naphthoquinone and vitamin K3 of the quinone compound 2-methoxy-1, 4-naphthoquinone are screened out. Wherein the 2-methoxy-1, 4-naphthoquinone serving as an inhibitor has a remarkable effect of inhibiting the combination of Dop and Pup, and IC50 (half maximal inhibitory concentration) ranges from 17.93 mu M to 34.55 mu M. The quinone compound 2-methoxy-1, 4-naphthoquinone and the derivative 2-bromo-1, 4-naphthoquinone and vitamin K3 thereof have a remarkable inhibition effect on mycobacterium tuberculosis, and can be applied to the development of antituberculosis drugs.

The present invention belongs to the technical field of biomedicine, relates to the extraction of active ingredients from traditional Chinese medicine, and relates to a polyhydroxy cembrane diterpenoid compound, its preparation method and application. The compound is compound 1 or compound 2, and the chemical structural formulas of compound 1 or compound 2 are shown as follows: The present invention extracts polyhydroxy cembrane diterpenoid compounds from frankincense, and through research, it is found that the polyhydroxy cembrane diterpenoid compounds have strong activity against liver injury caused by anti-tuberculosis drugs.

The invention provides a leucine dehydrogenase mutant and application thereof, and belongs to the technical field of bioengineering. The leucine dehydrogenase mutant provided by the invention can maintain higher catalytic stability in a wider pH value and temperature range, and the adaptability and durability of the leucine dehydrogenase mutant in an industrial reaction environment are remarkably improved. The improvement directly improves the efficiency and reliability of the process for catalytically synthesizing L-2-aminobutyric acid by using the enzyme, so that the reaction process is easier to control, and the cost loss caused by enzyme inactivation is potentially reduced. Finally, the mutant provides a catalyst with excellent performance for green, efficient and large-scale production of L-2-aminobutyric acid with high optical purity, so that a preparation process of chiral amino acid is simplified; and moreover, the method has important significance in reducing the production cost of key intermediates of downstream chiral drugs (such as certain antiepileptic drugs and antituberculosis drugs) and improving the product quality, and shows a good industrial application prospect.

The invention belongs to the technical field of medical equipment, and particularly relates to a portable tuberculosis drug aerosol inhalation device. The device comprises a medicine storage chamber, an outflow channel and a controller, the top of the medicine storage chamber is provided with a medicine tank groove with a conical pricking pipe, and one-step medicine filling through placing and pressing can be achieved; the respiratory rhythm of a user is identified through lip contact and a respiratory airflow sensor, and the atomizer is synchronously controlled to start and stop; the system has the functions of liquid medicine identity recognition, heating temperature control and self-adaptive power adjustment based on liquid medicine storage, efficient, safe and comfortable tuberculosis medicine inhalation treatment is achieved, and the medication compliance and the treatment effect are remarkably improved.

The invention provides a xanthohumol derivative in humulus lupulus as well as a preparation method and application thereof.The xanthohumol derivative is obtained by detecting and analyzing female flowers and fruits of humulus lupulus by thin-layer chromatography and analytical high-performance liquid chromatography, extracting with an organic solvent, and concentrating to obtain the xanthohumol derivative. And then separating through a solvent extraction method, macroporous adsorption resin column chromatography, normal-phase silica gel column chromatography, medium-pressure preparative chromatography, Sephadex LH-20 gel column chromatography and semi-preparative high performance liquid chromatography to obtain 22 new xanthohumol derivatives. 23 monomers are determined to be new xanthohumol derivatives through methods of high-resolution mass spectrum, nuclear magnetic resonance spectrum, circular dichroism spectrum, quantum chemistry calculation and the like, and structural identification is carried out on the new xanthohumol derivatives. Besides, the minimum concentration (MIC90) of Mycobacterium tuberculosis (Mtb) H37Ra is inhibited to evaluate the inhibition effect of the xanthohumol derivative on the Mtb H37Ra strain, and the xanthohumol derivative can be used for preparing antituberculosis drugs.

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 belongs to the field of biological medicines, and provides an application of acetoacetic acid and derivatives thereof in preparation of medicines for treating or relieving hepatotoxicity caused by antituberculosis medicines. The hepatocytes formed by differentiation of human induced pluripotent stem cells are verified, and hydrazine is a metabolite with the strongest toxicity, so that the content of acetoacetic acid in the metabolite in the cells is reduced. Acetoacetic acid is one of main ketone metabolites in the ketone metabolism process, and cells can convert acetoacetic acid into acetoacetyl coenzyme A through succinyl coenzyme A: 3-oxo acid coenzyme A transferase. According to the invention, the OXCT1 gene in the human induced pluripotent stem cell is knocked out through CRISPR-cas9 and the human induced pluripotent stem cell is differentiated into the hepatocyte, so that the knockout of the OXCT1 gene increases the content of acetoacetic acid and reduces hepatic differentiation cell death caused by hydrazine.

The invention provides application of chaetocin or a derivative thereof in preparation of a medicine. The medicine is used for (1) inhibiting growth or proliferation of mycobacteria; (2) killing or killing mycobacteria; (3) inhibiting mycobacterium infection; and / or (4) an anti-tuberculosis drug combination, the chaetocin has significant inhibitory activity on sensitive and drug-resistant mycobacterium tuberculosis and nontuberculous mycobacterium, has the advantages of high activity and low production cost, and provides a new choice for treatment of tuberculosis and nontuberculous mycobacterium diseases.

The invention relates to the technical field of bioengineering, in particular to a composition of a hypoxia inducible factor prolyl hydroxylase inhibitor and an antituberculosis drug and application of the composition. The composition of the hypoxia-inducible factor prolyl hydroxylase inhibitor and the antituberculous drug is applied to preparation of drugs or health-care products for preventing and treating chronic inflammatory anemia and infection, and the obtained drugs or health-care products can improve chronic inflammatory anemia caused by interference of mycobacterium tuberculosis. The medicine can be applied to treatment of tuberculosis and has a wide application effect.

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 discloses a near-infrared hydrazine fluorescent probe and a preparation method and application thereof, according to the method, the near-infrared hydrazine fluorescent probe (CY-NH) for specific detection of N2H4 is synthesized, and the probe is constructed on the basis of hemicyanine derivatives and 2-thiophene carbonyl. When the N2H4 exists, the 2-thiophene carbonyl part of the probe CY-NH and the N2H4 are subjected to selective deprotection reaction, so that a fluorophore CY-OH is released, strong fluorescence emission is displayed in a near-infrared fluorescence region, and specific detection of the N2H4 is realized. The invention provides application of the hydrazine fluorescent probe in hydrazine visual detection. The hydrazine fluorescent probe can be used for visual detection of gaseous N2H4 and in-situ detection of N2H4 produced by metabolism of an antituberculosis drug isoniazide (INH) in living cells and zebra fish. Compared with the prior art, the method disclosed by the invention is simple to operate, good in biocompatibility and convenient in post-treatment, and has a great application prospect in the aspect of hydrazine detection.