47 results about "Resistant tuberculosis" patented technology

Compositions and process are provided for the rapid and specific detection of drug resistant forms of Mycobacterium tuberculosis based on real time PCR and high resolution melt analysis. The compositions and processes are useful for the detection of mutations within the Rifampicin Resistance Determinant Region (RRDR) of rpoB for the detection of rifampicin (RIF) and within specific regions of katG and the inhA promoter for the detection of isoniazid (INH) resistance. The invention also is capable of rapidly discriminating Mycobacterium tuberculosis complex (MTBC) strains from Nontuberculous Mycobacteria (NTM) strains.

The invention discloses a pyrazolo[1, 5-a]pyridine compound with the structure characteristic shown in the formula (I) or its pharmaceutically acceptable salt, stereoisomer or prodrug molecule and a use thereof. The compound has good in-vitro anti-tubercle bacillus activity, has the minimal inhibitory concentration (MIC) less than 0.1 micrograms per milliliter and partial MIC of 0.01 micrograms per milliliter and has strong inhibition effects on a clinically sorted multi-drug-resistant tuberculosis (MDR-TB) strain. In an in-vivo experiment, at a dosage of 20mg / kg / d, the pyrazolo[1, 5-a]pyridine compound can effectively eliminate H37Ra infection in a mouse and is a novel anti-tuberculosis compound.

The invention discloses benzofuran and coumestans derivatives as shown in formulae (I|), (II) and (III) and a preparation method and an application thereof in treating multidrug-resistant tuberculosis. The benzofuran and coumestans derivatives are anti-mycobacterium tuberculosis compounds which are novel in structure and obvious in antibacterial effect. The compounds taking polyketone synthase coded by a mycobacterium tuberculosis pks13 gene fragment as an acting target spot inhibits growth and reproduction of microorganisms, in particular synthesis of mycolic acid in mycobacterium tuberculosis cell walls. The derivatives have a potential application prospect in the medical field.

The invention discloses an application of a quinine compound in preparing anti-tubercle bacillus drugs. A structure general formula of the quinine compound of the invention is shown in a formula (1), wherein R is H or OH. In the invention, aiming to current situations that the current tuberculosis has high morbidity, and multidrug-resistant tuberculosis (TB) strains of tubercle bacillus occur so that the morbidity and mortality of the tuberculosis are in a rising trend, and according to characteristics of anti-tubercle bacillus and tolerance tubercle bacillus activities of the quinine compound, the quinine compound is used for preparing the anti-tubercle bacillus drugs. The quinine compound of the invention is derived from marine microorganisms, is easy to be extracted, has low cost and wide application prospect, and can be used for preparing the anti-tubercle bacillus drugs.

The invention discloses a kit for detecting a tuberculosis treatment effect. The kit comprises the following reagents: (1) a fluorescence labeled anti-human CD4 (Cluster of Differentiation) antibody; (2) a fluorescence labeled anti-human CD154 antibody; and (3) a fluorescence labeled anti-human CD27 antibody. Compared with the traditional acid-fast stain or tubercle bacillus cultivation, the detection by utilizing the kit for identifying the tuberculosis treatment effect has the advantages of rapidness, simplicity and high sensitivity, and a tuberculosis treatment result can be obtained within two days just by taking 2ml of blood from a patient. The detection has a guidance effect on the clinical treatment of the tuberculosis (especially the drug-resistant tuberculosis).

The present invention is directed to 13C and / or 2H isotope enhanced ambroxol (“isotope enhanced ambroxol”) and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and / or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced ambroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and / or condition), especially an autophagy mediated disease state and / or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and / or conditions, especially of the lung. Methods of treating autophagy disease states and / or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.

The invention discloses an in-situ gel sustained-release preparation of Ranunculus ternatus Thunb. Its preparation method includes dispersing extract or crude powder of Ranunculus ternatus Thunb. as active component in aqueous solution. Adjuvant composition of the aqueous solution includes sodium alginate 0.1-3%, and hydroxypropyl methylcellulose 0.1-3%. The invention is favorable for pertinent intervention treatment of refractory, recurrent and multidrug-resistant tuberculosis, shortens cavity closure time, accelerates distal focus absorption, reduces recurrence and dissemination, and greatly improves curative rate of pulmonary tuberculosis.

The present invention relates to 4-pyrimidinylamino-benzenesulfonamide derivatives of general formula (I) and pharmaceutically acceptable salts, solvates, hydrates, regioisomeric and polymorphic forms thereof, processes for manufacturing of them, the use of them, as well as pharmaceutical compositions containing at least one of them as pharmaceutically active agent(s) together with pharmaceutically acceptable carrier, excipient and / or diluents, especially for the inhibition of polo-like kinases (PLKs) and the treatment of cancer. Said 4-pyrimidinylamino-benzenesulfonamide compounds have been also identified as new drug candidates for the prevention and / or treatment of infectious diseases like bacterial diseases e.g. tuberculosis, including the currently multidrug-resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) as well as for preventing tuberculosis.

The invention discloses an MTB (mycobacterium tuberculosis) rpoB mutant gene and an application thereof. Compared with a normal rpoB gene, the mutant gene has a c.1843G>A mutation site; a candidate gene screening method is adopted to detect 33 rifampicin-resistant tuberculosis strains in China, the gene mutation site is found for the first time, and the rpoB gene c.1843G>A mutation site in the rifampicin-resistant tuberculosis strains has certain occurrence frequency, so that the rpoB gene c.1843G>A mutation site can be taken as diagnostic basis of drug-resistance molecular mechanisms of rifampicin-resistant strains clinically.

The invention belongs to the technical field of tuberculosis diagnosis, and particularly discloses a recombinant protein for serodiagnosis of multimedicament-resistant tubercle bacilli. The recombinant protein is Rv1793 recombinant protein, and is obtained by the following steps of: inserting Rv1793 into the position between Pet28a EcoRI and HindIII endonuclease sites to form a recombinant plasmid, transforming the recombinant plasmid into E. coli BL21 to form recombinant E. coli, and expressing the protein. The sensitivity of the novel recombinant protein on the serodiagnosis of medicament resistance can reach 75 percent, and is far more than 53.3 percent of diagnosis rate of medicament resistance of a control CFP-10 recombinant protein. The Rv1793 recombinant protein becomes an effective biomarker applied to the serodiagnosis of medicament-resistant tuberculosis.

The invention relates to a compound Chinese medicine for treating multidrug-resistant tuberculosis, which is prepared from following raw medicinal materials: 15 to 20 grams of manyflower solomonseal rhizome, 10 to 20 grams of common bletilla tuber, 15 to 20 grams of heterophylly falsestarwort root, 10 to 15 grams of sessile stemona root, 15 to 20 grams of Japanese ardisia herb, 10 to 15 grams of common coltsfoot flower, 15 to 20 grams of Phippine violet herb, 10 to 12 grams of Japanese thistle herb or root, 15 to 20 grams of cochinchinese asparagus root, and 15 to 20 grams of turtle shell. The compound Chinese medicine capable of treating multidrug-resistant tuberculosis can enhance a curative effect, and has functions of nourishing Yi, moistening lung, killing parasites, eliminating phlegm, removing blood stasis and promoting tissue regeneration. The compound Chinese medicine provided by the invention integrates a western chemotherapy regimen to treat multidrug-resistant tuberculosis, and also can accelerate sputum conversion, promote the absorption of focus, improve immunity, and accelerate the recovery of tuberculosistoxic symptoms.

The invention discloses a new quinoline derivative shown as the structural general formula (I) in the specification, a preparation method thereof, pharmaceutical compositions containing the same, and application thereof as an antituberculosis drug. The invention also relates to physiologically acceptable inorganic acid or organic acid composed salts, N-oxide. The compounds have excellent antituberculosis activity, and can be used as drugs for treatment of tuberculosis including multidrug resistant tuberculosis. (formula (I)).

A combined drug for inhibiting multidrug-resistant tuberculosis bacilli comprises ethyl acetate fraction of forsythiae, isoniazid and rifampicin for simultaneous or separate administration, and pharmaceutically acceptable carriers. The combined medicine of the invention can obviously reduce the dosage of isoniazid and rifampicin, remarkably increase the synergistic bacteriostatic effect, thereby reducing the toxic and side effects of isoniazid and rifampicin, increasing the medication compliance of patients, and providing a new choice for clinic.

The invention discloses a method for rapidly optimizing a traditional Chinese medicine formula and application of the traditional Chinese medicine formula in drug-resistant tuberculosis resistance. The method for optimizing the drug-resistant tuberculosis formula comprises the following steps: respectively performing alcohol extraction on an existing tuberculosis formula and single medicines consisting of the tuberculosis formula, thereby obtaining a formula alcohol extract and a single medicine alcohol extract; respectively performing tubercle bacillus antibacterial effect detection on the formula alcohol extract and the single medicine alcohol extract, thereby obtaining the minimum antibacterial concentration of the existing tuberculosis formula and the single medicines; selecting the following single medicines which meet any condition for compounding, thereby obtaining the optimized tuberculosis formula: the single medicine of which the minimum antibacterial concentration is less than or equal to 500 and which is non-toxic, and the single medicine of which the minimum antibacterial concentration is greater than 500 and which is non-toxic when entering lung channels; and expanding drug-resistant bacterium detection of the optimized tuberculosis formula, thereby obtaining an improved formula, namely the drug-resistant tuberculosis formula, which has an obvious antibacterial effect compared with the existing tuberculosis formula. The obtained drug-resistant tuberculosis formula has an obvious antibacterial effect on tubercle bacillus, particularly drug-resistant tubercle bacillus, can be effectively used for treating pulmonary tuberculosis, particularly drug-resistant pulmonary tuberculosis and the like, and is safe and free of toxic or side effect.

The present invention relates to the field of anti-mycobacterial therapeutics, in particular the treatment of tuberculosis, especially including pulmonary multidrug-resistant tuberculosis (MDR-TB), with applications in extensively drug-resistant tuberculosis (XDR-TB) and extremely drug-resistant tuberculosis (XXDR-TB), preferably in combination therapy.

The present invention belongs-the technical field of biomedicines and provides a mycobacterium tuberculosis mutant gene and an application thereof. The mutant gene is a mutant gene in which an Rv1527cgene fragment is deleted in a H37Rv gene of a standard strain of mycobacterium tuberculosis, or a mutant gene with an alanine at 1380th position on the Rv1527c gene fragment of the mycobacterium tuberculosis is mutated to proline or glycine at 1637th position is mutated to alanine. The mutant gene is used as a biomarker of the mycobacterium tuberculosis for detection of clinical specimens of tuberculosis patients before treatment and conducive-clinical formulation of reasonable chemotherapy regimens, and thus improves a clinical successful treatment rate of tuberculosis patients, especially multidrug-resistant tuberculosis patients.

The invention provides a rifampicin drug-resistant tuberculosis molecular marker, a detection reagent and an application thereof. Involved in the field of biomedical technology. The molecular markers include TRIM9, TRIM21 and TRIM56 genes and expression products thereof; the expression of the TRIM9, TRIM21 and TRIM56 genes is down-regulated in rifampicin-resistant tuberculosis patients. The invention can quickly, efficiently and sensitively identify rifampicin drug-resistant tuberculosis patients, and can be used for the screening of rifampicin drug-resistant tuberculosis.

The invention discloses an application of a quinine compound in preparing anti-tubercle bacillus drugs. A structure general formula of the quinine compound of the invention is shown in a formula (1), wherein R is H or OH. In the invention, aiming to current situations that the current tuberculosis has high morbidity, and multidrug-resistant tuberculosis (TB) strains of tubercle bacillus occur so that the morbidity and mortality of the tuberculosis are in a rising trend, and according to characteristics of anti-tubercle bacillus and tolerance tubercle bacillus activities of the quinine compound, the quinine compound is used for preparing the anti-tubercle bacillus drugs. The quinine compound of the invention is derived from marine microorganisms, is easy to be extracted, has low cost and wide application prospect, and can be used for preparing the anti-tubercle bacillus drugs.

The invention provides a pyridone derivative and its use in the preparation of medicines for preventing and / or treating tuberculosis caused by Mycobacterium tuberculosis, belonging to the field of pharmacy. The structure of the pyridone derivative is shown in formula (I). Experimental results show that the pyridone derivatives provided by the present invention can specifically inhibit the activity of Mycobacterium tuberculosis, and have little toxic and side effects, can be used to prepare anti-Mycobacterium tuberculosis drugs, and can also be used to prepare preventive and / or Drugs for treating tuberculosis provide a new option for drugs for treating tuberculosis (especially drug-resistant tuberculosis).

The invention discloses the use of hsa-miRNA-423-5p in the preparation of an autophagy maturation inhibitor, and the use of the hsa-miRNA-423-5p inhibitor in the preparation of a drug for treating tuberculosis. The expression level of hsa-miRNA-423-5p provided by the present invention in the serum of tuberculosis patients is significantly higher than that of healthy controls, and it is confirmed that when hsa-miRNA-423-5p is highly expressed, it can lead to obvious autophagy maturation blocking phenomenon; hsa When the expression of ‑miRNA‑423‑5p is inhibited, the phenomenon of autophagy maturation inhibition is relieved. Therefore, hsa‑miRNA‑423‑5p can be used as a good target for the treatment of tuberculosis. Moreover, hsa-miRNA-423-5p is a small molecule that exists by itself, so it is superior to chemical drugs in terms of side effects, and will not cause drug-resistant tuberculosis due to repeated medication.

The invention relates to a compound Chinese medicine for treating multidrug-resistant tuberculosis, which is prepared from following raw medicinal materials: 15 to 20 grams of manyflower solomonseal rhizome, 10 to 20 grams of common bletilla tuber, 15 to 20 grams of heterophylly falsestarwort root, 10 to 15 grams of sessile stemona root, 15 to 20 grams of Japanese ardisia herb, 10 to 15 grams of common coltsfoot flower, 15 to 20 grams of Phippine violet herb, 10 to 12 grams of Japanese thistle herb or root, 15 to 20 grams of cochinchinese asparagus root, and 15 to 20 grams of turtle shell. The compound Chinese medicine capable of treating multidrug-resistant tuberculosis can enhance a curative effect, and has functions of nourishing Yi, moistening lung, killing parasites, eliminating phlegm, removing blood stasis and promoting tissue regeneration. The compound Chinese medicine provided by the invention integrates a western chemotherapy regimen to treat multidrug-resistant tuberculosis, and also can accelerate sputum conversion, promote the absorption of focus, improve immunity, and accelerate the recovery of tuberculosistoxic symptoms.

The invention provides a fusion protein and its use for treating tuberculosis. The fusion protein can specifically induce apoptosis of macrophages that phagocytose Mycobacterium tuberculosis, thereby killing endoparasites without inducing bacterial drug resistance . Therefore, the treatment of tuberculosis, especially drug-resistant tuberculosis, will play an important role.

The present invention relates to the field of anti-mycobacterial therapeutics, in particular the treatment of tuberculosis, especially including pulmonary multidrug-resistant tuberculosis (MDR-TB), with applications in extensively drug-resistant tuberculosis (XDR-TB) and extremely drug-resistant tuberculosis (XXDR-TB), preferably in combination therapy.

The invention relates to application of boningmycin in treatment of drug-resistant tuberculosis, in particular to application of the boningmycin or pharmaceutically acceptable salts thereof in preparation of drugs. The drugs are used for (1) inhibiting growth or proliferation of mycobacterium tuberculosis; (2) killing or damaging the mycobacterium tuberculosis; (3) inhibiting mycobacterium tuberculosis infection; and / or (4) treating diseases caused by the mycobacterium tuberculosis infection. Results show that the boningmycin has remarkable inhibitory activity on sensitive and drug-resistant mycobacterium tuberculosis, has the advantages of high activity and low production cost, and provides a new choice for tuberculosis treatment.

The invention provides a rifampicin drug-resistant tuberculosis molecular marker, a rifampicin drug-resistant tuberculosis detection reagent and application thereof, and relates to the technical field of biomedicine. The molecular marker comprises a TRIM9 gene, a TRIM21 gene, a TRIM56 gene and expression products of the TRIM9 gene, the TRIM21 gene and the TRIM56 gene. The expression of the TRIM9, TRIM21 and TRIM56 genes in a rifampicin drug-resistant tuberculosis patient is reduced. The rifampicin drug-resistant tuberculosis molecular marker can be used for identifying rifampicin drug-resistant tuberculosis patients more quickly, efficiently and sensitively, and can be used for screening rifampicin drug-resistant tuberculosis.

The invention provides a pyridone derivative and application thereof in preparation of a medicine for preventing and / or treating tuberculosis caused by mycobacterium tuberculosis, which belong to the field of pharmacy. The structure of the pyridone derivative is shown as a formula (I). Experimental results show that the pyridone derivative provided by the invention can specifically inhibit the activity of mycobacterium tuberculosis, has small toxic and side effects, can be used for preparing a medicine for resisting mycobacterium tuberculosis, can also be used for preparing a medicine for preventing and / or treating tuberculosis, and a new choice is provided for medicines for treating tuberculosis (especially drug-resistant tuberculosis).

The invention discloses a capreomycin dry powder inhalant and a preparation process thereof. The capreomycin dry powder inhalant comprises capreomycin sulfate powder, a dry powder carrier and filling capsules, wherein the component of the dry powder carrier is ML003 lactose; and the filling capsules are 3#HPMC capsules with the specification of 12.5 mg / capsule. The capreomycin dry powder inhalant can be used for effectively curing the tuberculosis or multidrug-resistant tuberculosis patients, enables drugs to directly act on sputum-derived bacteria due to inhalation administration, and is expected to quickly kill bacteria.

The invention discloses a preparation method and application of a MC-ARMS-mMB triplet technology in a drug-resistant tuberculosis diagnosis kit, and describes the MC-ARMS-mMB (microcolony-amplification-impeding mutation system-multiplex molecular beacon) triplet technology , a diagnostic kit for rapid culture of Mycobacterium tuberculosis and its drug-resistant bacteria. At the same time, the preparation method of the diagnostic kit was clarified; and a scientific presentation was made on its clinical application. It is particularly important to point out the clinical application value and better development prospect of the diagnostic kit.