80 results about "Antitubercular Agent" patented technology

The invention discloses streptomyces atratus and application of cyclic peptide compounds with the same to preparing mycobacterium tuberculosis resistant medicines. A structural formula of the cyclic peptide compounds is shown. A preservation number of the streptomyces atratus SCSIO Zh16 is CGMCC No.12198. The streptomyces atratus and the application have the advantages that the six cyclic peptide compounds are obtained from fermentation cultivation substances of the streptomyces atratus SCSIO Zh16 by means of separation, the cyclic peptide compound 6 is high in mycobacterium tuberculosis resistant activity, obvious effects of inhibiting mycobacterium tuberculosis can be realized by the cyclic peptide compound, accordingly, the cyclic peptide compounds can be used for preparing anti-tuberculosis medicines and can be used for treating tuberculosis, alternative compounds can be provided for developing novel anti-tuberculosis medicines, and the streptomyces atratus and the application have important significance on developing marine medicinal materials in China.

The invention belongs to the medicine field, and particularly relates to benzothiazinethione derivatives and preparation methods and uses thereof. In the aspect of the present invention, novel benzothiazinethione derivatives of formula I are provided, the benzothiazinethione derivatives of the invention are new compounds obtained based on extensive screening. Experimental results show that the benzothiazinethione derivatives of formula I have obvious inhibitory effects on mycobacterium tuberculosis, with effects equivalent to or even better than that of isoniazide (MIC 90 =0.8µM). The benzothiazinethione derivatives of formula I have anti-mycobacterium tuberculosis activities, and provide new choices for the development and application of antitubercular agents.

The present invention provides a method for identifying Mycobacterium tuberculosis and non-tuberculosis Mycobacterium (MOTT), and for the determination of drug susceptibility of M. tuberculosis based on detection of mutations in the rpoB gene.

The invention discloses a mycobacterium tuberculosis medicament sensitive phenotype detection method, which comprises the following steps of: 1) adding 2.5 to 6mul of 0.2 percent of resazurin dissolved by using methanol with mass percentage concentration into the inner side of a tube cover of a sterile centrifuge tube, and sterilizing the centrifuge tube after the methanol is volatilized; 2) inoculating 5 to 50mg of mycobacterium tuberculosis to be detected into a 7H9-S culture medium, regulating the concentration of the bacteria solution by adopting turbidimetry, regulating the concentration of the bacteria solution to the concentration of a Mcburney turbidimetric 1 tube by using sterile water or 0.9-percent physiological saline, and diluting the bacteria solution by 20 times by using the 7H9-S culture medium; 3) inoculating 50 to 150mu of diluted bacteria solution into the centrifuge tube of the step 1); 4) adding 100mul of anti-tubercular medicament solution diluted by 7H9-S and to be detected into the centrifuge tube of the step 3), wherein the concentration of the medicament to be detected is 0.01mug / ml to 2.5mg / ml; 5) after the centrifuge tube of the step 4) is covered closely, culturing the solution for 6 to 7 days at the temperature of 37 DEG C; and 6) inverting and oscillating the centrifuge tube of the step 5), and culturing the solution for 12 to 48 hours at the temperature of 37 DEG C after the solution becomes blue. Proved by experiments, in the mycobacterium tuberculosis medicament sensitive phenotype detection method and application of the mycobacterium tuberculosis medicament sensitive phenotype detection method in anti-tubercular medicament screening, the method has low workload and short detection time; compared with a traditional L-J medium medicament sensitive detection method, the accuracy reaches 90 to 99 percent; and the method has good biological safety, does not cause laboratory propagation of tuberculosis, is suitable for large-scale.

The invention discloses a mycobacterium drug sensitive detection kit which is safe and effective, convenient to operate, short in testing time and wide in testing drug range and a testing method thereof. The mycobacterium drug sensitive detection kit provided by the invention comprises a kit body (1), wherein the kit body (1) internally comprises a plurality of drug sensitive culture mediums (2), a drug sensitive testing plate (3), a sterile suction nozzle (4), a sterile diluent (5), an infectious microbe inhibitor (6), a specification and a report label, the drug sensitive culture medium (2) comprises a basal culture medium, a growth promoter and a bacteriostatic agent, and a negative control hole (31), a positive control hole (32) and a plurality of drug containing holes (33) are formed in the drug sensitive testing plate (3), wherein the drug containing holes (33) are arranged into a matrix and are coated with different antituberculosis drugs. The mycobacterium drug sensitive detection kit can be applied to the field of mycobacterium tuberculosis detection.

The present invention relates to applications of Mycobacterium tuberculosis antigen protein Rv0446c and a T-cell epitope peptide thereof in preparation of tuberculosis detection reagents, vaccines and medicines, wherein the amino acid sequences of the antigen protein Rv0446c and the T-cell epitope peptide thereof are respectively represented by SEQ ID NO:1-5. According to the present invention, the Mycobacterium tuberculosis antigen protein Rv0446c and the T-cell epitope peptide thereof are used as the stimulants for the specific T cell and B cell immune response caused by Mycobacterium tuberculosis infection, and the false positive caused by the impure antigen can be reduced compared with the use of the complete antigen in the prior art; and the detection reagents prepared from the antigen protein Rv0446c and the T-cell epitope peptide thereof can be widely used for assisted diagnosis of tuberculosis, epidemiological surveillance and other related fields, and the tuberculosis vaccines and the anti-tuberculosis drugs prepared from the antigen protein Rv0446c and the T-cell epitope peptide thereof can be used for prevention and treatment of tuberculosis.

The invention relates to a substituted 1,3-miscellaneous azole compound, a preparation method thereof, a pharmaceutical composition containing the substituted 1,3-miscellaneous azole compound and a purpose thereof. The invention relates to the compound in a formula I, or its pharmaceutically acceptable salt, a stereisomer or a solvate, wherein R1, R2, R3 and X are defined as a specification; and the invention also relates to the preparation method, the pharmaceutical composition containing the substituted 1,3-miscellaneous azole compound and the purpose thereof. The compound of the present invention is the novel antituberculous compound, is effective to mycobacterium tuberculosis-susceptible strains, also possesses activity on strains with tolerance on traditional first-line antituberculous drugs such as isoniazide and rifampicin, and has good selectivity to mycobacterium tuberculosis.

N-acetylglucosamine-1-phosphate transferase is a key component for synthesis of cell wall of M.tuberculosis (MTB), and wec A gene is an encoding gene of the N-acetylglucosamine-1-phosphate transferase, the invention constructs a wec A gene knock-out strain MJ2008 (Mycobacterium smegmatis), CGMCC 3417 and takes the MJ2008 strain as a cell model for screening the N-acetylglucosamine-1-phosphate transferase in a high throughout so as to screen out the effective N-acetylglucosamine-1-phosphate transferase inhibitor from a combined compound library and the traditional Chinese medicine and prepare the anti-tuberculosis drug with a high efficiency; additionally, in human cells, there has no homologue of the MTB N-acetylglucosamine-1-phosphate transferase, accordingly, the developed anti-tuberculosis drug targeting the N-acetylglucosamine-1-phosphate transferase has no harm to the human body and overcomes the disadvantage of killing normal cells of antibacterial agents.

The present invention relates to a 1-substituted-4-nitroimidazole compound represented by the general formula (1) or a salt thereof, (wherein R is a hydrogen atom, a lower alkoxy group-substituted lower alkyl group, a phenyl-lower alkoxy group-substituted lower alkyl group, a cyano-substituted lower alkyl group, a phenyl-lower alkyl group which may have lower alkoxy groups as the substituents in the phenyl ring or a group of the formula —CH2RA; X is a halogen atom or a group of the formula —S(O)n—R1) and method for preparing the same. The compound of the formula (1) is a useful compound as an intermediate for synthesis of various pharmaceutical and agricultural chemicals, particularly, as intermediates for antitubercular agents.

The invention provides a method for simultaneously measuring content of three antitubercular agents (retozide, rifampicin and pyrazinamide) in blood and tissues. The method has the characteristics of simplicity and convenience in operation, high precision, high detection speed, stability and reliability. A high-efficient liquid-phase chromatographic instrument (LC2010C), a column temperature control box AT-130 and an Lc-solution spectrum work station of the Japan Shimadzu Company are adopted. The chromatographic column is an analysis column and adopts a C8 column, the protection column adopts a C18 column, and the fluid phase adopts sodium 1-heptanesulfonate solution to prepare.

The invention discloses a mycobacterium tuberculosis surface lipolysaccharide-antistatic nucleic acid aptamer and application thereof. The aptamer is a small molecular single-stranded deoxyribonucleic acid (ssDNA) which is specific to toxic mycobacterium tuberculosis surface lipolysaccharide ManLAM (Mannosylated Lipoarabinomannan) and has tuberculosis infection resisting and cellular immunity enhancing functions, and the nucleotide sequence of the ssDNA is shown as SEQIDNo.1. The small molecular ssDNA has a novel target spot and a novel structure which are different from those of the conventional anti-tuberculosis medicament, and has the immunologic suppression function of directly enclosing the ManLAM. The aptamer is easy to prepare and has low price; the obtained ssDNA aptamer is specifically combined on the surface of toxic mycobacterium tuberculosis; and the treatment targeting is further enhanced. The problems of increasing medicament tolerance and large side effect existing in the conventional treatment of tuberculosis are solved, and the aptamer can be taken as an effective novel anti-tuberculosis medicament or a tuberculosis diagnosis reagent.

The invention relates to a mycobacterium tuberculosis antigen protein Rv0865 and an application of a B cell epitope peptide thereof in preparing a tuberculosis detection reagent, a vaccine and a drug. The amino acid sequences of the antigen protein Rv0865 and the B cell epitope peptide thereof are respectively shown as SEQ ID NO: 1-5. According to the invention, the mycobacterium tuberculosis antigen protein Rv0865 and the B cell epitope peptide thereof are utilized as stimulants for specific T cell and B cell immune response caused by mycobacterium tuberculosis infection. Compared with the traditional condition adopting complete antigen, the false positive caused by impure antigen can be reduced. The detection reagent prepared by adopting the protein Rv0865 and the epitope peptide thereof can be widely applied to the field of phthisic auxiliary diagnosis and epidemic disease monitoring. The vaccine and the drug prepared by adopting the protein Rv0865 and the epitope peptide thereof can be used for preventing and treating tuberculosis.

The invention relates to a device and a method for preparing a gel microsphere and a gel microsphere in which antitubercular agents can be injected. The device comprises: a porous shower nozzle, a collecting cup, a collecting tubule, a high pressure static generator, a constant current pump, a settling basin, an injection pump and an infiltration electrode. On the basis of a common static liquid drop generating device, the collecting tubule is arranged to form a liquid level flow regulating system, so that a liquid exchange passage exists between the collecting cup and the settling basin and can collect the low-density gel microspheres floating on the liquid level of the collecting cup and rapidly transfer the microspheres to the settling basin. Meanwhile, the built-in infiltration electrode type porous shower nozzle can enable the drug liquid droplet in drug-carrying sol solution to be fully charged, and form a uniform high electric field with the collecting tubule, thus enhancing the atomizing effect of the liquid column of the nozzle and enabling the drug-carrying sol solution to form monodispersity gel microspheres. The gel microsphere in which antitubercular agents can be injected contains rifapentine or rifabutin, made by the device and the method. The gel microsphere is high in yield, and large in drug-carrying capacity, and does not sink down or adhere after drying.

The invention relates to a tuberculosis mycobacterium drug resistance gene detection kit and its preparation method. The kit is prepared by the following steps: designing and synthesizing corresponding oligonucleotide probes according to different mycobacteriums and tuberculosis mycobacterium complex 16S ribosome ribonucleic acids (rRNA), dotting the oligonucleotide probes according to certain sequence on the pretreated nitrate fiber film by dot plot method, then obtaining drug resistance gene detection identification film sheet, and hybridizing with the PCR amplification products having biotin marks. According to the bluish purple signal strength of the probes hybridization to interpret the result with naked eyes, the invention can be used for detecting five drug resistance genes of tuberculosis mycobacterium of clinical specimens or clinical separation strains.

The invention relates to N-benzylbenzamide compounds represented by formula (I), a preparation method and a medicinal use thereof, and an anti-tuberculosis medicinal composition adopting the compounds as an effective component. The N-benzylbenzamide compounds are concretely characterized in that a substituent group in the para-position of a benzyl group of the N-benzylbenzamide compounds is a nitrogen-containing heterocyclic segment; and in the formula (I), R represents a trifluoromethyl group or a nitro group, and X represents a 4-thiomorpholinyl group, an octahydro-2H-isoindole-2-yl group, an isoindoline-2-yl group, a 4-substituted piperidine-1-yl group, a (4-substituted phenyl)piperidine-1-yl group or a (4-substituted phenyl)piperazine-1-yl group.

The invention discloses a substituted N-((1', 3'-azole-4'-yl)-methyl)-4-benzoyl-hexahydropyridine compound represented by formula I, a preparation method thereof, and applications of the substituted N-((1', 3'-oxazole-4'-yl)-methyl)-4-benzoyl-hexahydropyridine compound in preparation of antituberculous drugs. The substituted N-((1', 3'-azole-4'-yl)-methyl)-4-benzoyl-hexahydropyridine compound possesses activity on mycobacterium tuberculosis-susceptible strains, and also possesses activity on strains with tolerance on traditional first-line antituberculous drugs such as isoniazide and rifampicin, and is a novel mycobacterium tuberculosis resistant compound with a promising application prospect.

The invention belongs to the field of microbial biotechnology, in particular to application of a mycobacterium tuberculosis Rv1354c gene (a gene sequence and encoded protein) as an anti-tuberculous medicament target. The application range thereof comprises: (1) simulating a three-dimensional structure of a mycobacterium tuberculosis Rv1354c guanylic acid cyclase structure domain; (2) establishing a computer medicament screening system specific to the mycobacterium tuberculosis Rv1354c; and (3) applying the computer medicament screening system in the step (2) to screen 16 compounds with high affinity with active sites from a ZINC database, and providing a basis for researching and developing new anti-tuberculous medicaments.

The invention provides a drug-resistant gene of mycobacterium tuberculosis and an application of the drug-resistant gene of the mycobacterium tuberculosis. The drug-resistant gene is used for coding any one of the following proteins: i) a protein sequence including an SEQ ID No. 2 sequence in an amino acid and / or nucleotide sequence table; and ii) a protein sequence derived by replacing, deleting or superposing one or more amino acids in sequence (i), and provided with the same function as sequence i). According to a drug sensitivity test, the drug-resistant gene can be used for enabling bacteria to generate drug resistance to various anti-tuberculosis drugs.

The invention discloses a glmM gene knock-out bacterial strain ML2009 (mycobacterium smegmatis), CGMCC (China General Microbiological Culture Collection Center) 3418, which is constructed by using phosphoglucomutase participating in the biosynthesis of key components in a mycobacterium tuberculosis cell wall. The bacterial strain ML2009 can be used as a cell model for sieving phosphoglucomutase inhibitors with high flux, be used for sieving effective phosphoglucomutase inhibitors from a combined compound library, traditional Chinese medicine and natural products to prepare tuberculosis-resisting medicaments with high medicine effects; and in addition, in the cells of a human body, the synthesis approach of UDP (Uridine Diphosphate)-acetyl glucosamine is different from that of mycobacterium tuberculosis, no phosphoglucomutase exists in the UDP-acetyl glucosamine, therefore, the reaction catalyzed by the mycobacterium tuberculosis phosphoglucomutase does not exist in the cells of the human body so that the tuberculosis-resisting medicaments developed by using the phosphoglucomutase as a target enzyme are harmless to the human body, and the defect that the traditional antibacterial medicament also kill normal cells is overcome.

The invention discloses an application of a fluorine-containing catechol structure compound serving as a mycobacterium tuberculosis inhibitor. The application is the specific application of the fluorine-containing catechol structure compound in preparing medicine for treating and / or preventing disease caused by mycobacterium tuberculosis inflection. Experiments show that the fluorine-containing catechol structure compound (such as 3-fluorocatechol) has the direct inhibiting effect on growth of mycobacterium tuberculosis, proliferation of the mycobacterium tuberculosis in macrophage can be inhibited, and the expression level of nitric oxide in the macrophage inflected by the mycobacterium tuberculosis can be improved. In addition, cytotoxicity tests also show that the fluorine-containing catechol structure compound (such as the 3-fluorocatechol) is free of obvious toxic and side effects, and in cell pharmacodynamics tests, in the effective dose range, obvious toxicity change of cells does not appear. Therefore, the fluorine-containing catechol structure compound is of great significance in researching and developing novel antituberculosis medicine.

The invention provides a marine fungus derived azaphilones dimer compound and an application thereof in anti-tuberculosis medicaments, wherein the structural formula of the compound is shown in formula 1 or formula 2. Fermenting culture is carried out on an HBU-135 strain of pleosporales sp., and the compound is isolated from the fermentation product. Proved by verification, the compound providedby the invention has high inhibitory activity on multi-drug-resistant mycobacterium tuberculosis (MDR-TB), can be used as an anti-tuberculosis medicament, and has a wide application prospect.

The invention discloses a method for detecting whether a patient is allergic to a medicine, which comprises the following steps: 1) dissolving a possibly allergic medicine to be detected, which is used as a solute, in a solvent to prepare a detection agent of which the concentration is 5-40%; and 2) carrying out allergy testing on a patient by using the obtained agent according to the medicine patch test. The possibly allergic medicine to be detected is an antitubercular agent, and a solvent is vaseline or water. The method can obviously enhance the transdermal absorptivity of the medicine. The clinical verification and in-vitro experimentation prove that the anaphylaxis of the medicine patch test is up to 68.7%, the specificity is up to 82.5%, and all cases do not have systemic adverse reaction.

An antimycobacterial combination and composition for treating tuberculosis are described. The compounds used are N-(3-[[4-(3-trifluoromethylphenyl)piperazinyl]methyl]-2-methyl-5-phenyl-pyrrolyl)-4-pyridylcarboxamide of formula (I) or a pharmaceutically acceptable non-toxic salt thereof and an amount of one or more first line antitubercular drugs.

The invention relates to the technical field of medical detection, in particular to a primer, a probe and a kit for detecting mycobacterium tuberculosis and drug-resistant gene mutation sites. The detection primer and the probe comprise DNA (deoxyribonucleic acid) sequences as shown in SEQ ID NO: 1 to SEQ ID NO: 68. The drug resistance type of mycobacterium tuberculosis is detected based on a Luminex liquid chip, whether the mycobacterium tuberculosis exists in a sample or not can be detected, four first-line antituberculous drugs including isoniazide, rifampicin, pyrazinamide and streptomycin and a second-line antituberculous drug, namely fluoroquinolone, are covered, mutation sites are comprehensive, the detection speed is high, only 3.5 hours are needed to complete one-time detection, and as many as 96 samples can be detected at the same time at one time. Therefore, the detection process is simplified, the experimental period is shortened, the detection accuracy and sensitivity are improved, and clinical application is facilitated.

The invention belongs to the field of biotechnology, and specifically relates to expression purification, a crystal structure and an application of a mycobacterium tuberculosis ribosomal protein S7. The protein S7 contains 156 amino acids, has the molecular weight of about 17.6 kDa, and has the isoelectric point of about 10.56; the protein S7 has high soluble expression in an expression strain escherichia coli rosetta (DE3), and has good purity and homogeneity. A three-dimensional structure of the ribosomal protein S7 is obtained by an X-ray diffraction method; the resolution ratio reaches up to 1.80 Angstroms; the space group is P2[1]2[1]2[1]. The structure is integrally composed of 6 alpha spirals and 2 beta spirals, wherein an alpha spiral beam structure composed of alpha spiral 1, alpha spiral 2, alpha spiral 3, alpha spiral 4 and alpha spiral 5 has interaction with other proteins on other ribosomes; a beta hairpin structure connected between alpha 3 and alpha 4 has an RNA recognition function. The three-dimensional structure of the ribosomal protein S7 has broad application prospects in screening of novel anti-tuberculosis drugs.

A pharmaceutical formulation is provided comprising combination of anti-tuberculosis drug drugs optionally in combination of bioenhancers. The formulation is used for the treatment of diseases caused by mycobacterium tuberculosis. The process of preparation of the formulation is also provided.

The present invention relates to an in vivo drug screening method taking advantage of the yeast two-hybrid system provides a method of using the whiB genes which are regulatory genes of mycobacteria, whose functions have not been reported so far, as drug target by using the yeast Saccharomyces cerevisiae as a surrogate host.

The present invention discloses functional nitrite reductase as a potential drug target for anti-tubercular drug development. The present invention also relates to the development of an easy method for identification of nitrite in clinical samples as well as its correlation with the severity of the disease. Presence of active as well as dormant / latent stages of Mycobacterium tuberculosis (MTB) could be identified from nitrite in clinical samples like sputum of potential TB patients.