115 results about "Antituberculosis drug" patented technology

The invention discloses conjugates of dihydroartemisinin and quinolones compounds shown in formulae I to IV and officinal salt thereof, wherein X is -CH2CH2-, -CH2CH2CH2- or -COCH2CH2CO-. The conjugates have a certain antibacterial effect on a mycobacterium tuberculosis standard sensitive strain, a clinical separating sensitive strain and a clinical separating drug resistance strain, and especially the inhibitory effects of conjugates of dihydroartemisinin and clinafloxacin on the mycobacterium tuberculosis standard sensitive strain, the clinical separating sensitive strain and part of the clinical separating drug resistance strain are stronger than those of independent dihydroartemisinin and clinafloxacin. The conjugates can be used for preparing antituberculosis drugs and have a potential application prospect in tuberculosis prevention and cure field. The formulae I to IV are as shown in the specification.

The invention discloses conjugates of dihydroartemisinin and quinolones compounds shown in formulae I to IV and officinal salt thereof, wherein X is -CH2CH2-, -CH2CH2CH2- or -COCH2CH2CO-. The conjugates have a certain antibacterial effect on a mycobacterium tuberculosis standard sensitive strain, a clinical separating sensitive strain and a clinical separating drug resistance strain, and especially the inhibitory effects of conjugates of dihydroartemisinin and clinafloxacin on the mycobacterium tuberculosis standard sensitive strain, the clinical separating sensitive strain and part of the clinical separating drug resistance strain are stronger than those of independent dihydroartemisinin and clinafloxacin. The conjugates can be used for preparing antituberculosis drugs and have a potential application prospect in tuberculosis prevention and cure field. The formulae I to IV are as shown in the specification.

The invention relates to application of kelimycin in mycobacterium tuberculosis infection resistance. The application comprises the following main steps: clinical first-line antitubercular drugs isoniazide and rifamycin are used as contrast, and the antimycobacterial activity of kelimycin is detected by adopting an absolute concentration method. The result indicates that the activity of kelimycin on clinically separated mycobacterium tuberculosis including drug-resistance bacteria is remarkably superior to those of the clinical first-line contrast drugs isoniazide and rifamycin, and novel application of kelimycin is expected to be developed in treatment of tubercle bacillus infected diseases.

The invention discloses a degradable orthopedics drug carrier system with osteo inductivity and a preparation method thereof. The drug carrier system essentially consists of the carrier material which is biological activity glass setting solid and the carried therapeutic drug. And the carrier material is the solid body carrier material with certain strength which is obtained through the fast curing after the reaction of highly reactive boron-containing biological activity glass and cured buffer liquid after the reaction. The carrier material can carry various drugs without thermal stability restriction, such as antibiotics, bone growth factors, antituberculosis drugs, antineoplastic drugs, which are used for the treatment of orthopedics diseases, thus composing the integrated drug carrier system. The drug carrier system can degrade automatically under the function of human tissue fluid in a human body with a porous structure left during the degradation which provides diffusion channels for the sustainable releasing of the drugs, thus achieving the effect that the drugs are chronically and uniformly released. The drug carrier system has good biocompatibility, biological activity and osteo inductivity and can be applied to the treatment of various diseases of orthopedics.

The present invention belongs to the field of screening antituberculotic target, vaccine antigen and detecting target in molecular biological technology, and is especially process of screening protein resisting rifampicin as antituberculotic. The process includes the first culturing drug resistant strain, the subsequent separating protein of drug resistant strain from protein of sensitive strain, comparing protein of drug resistant strain and protein of sensitive strain to determine the drug resistant protein, and final separating and identifying drug resistant protein. The process of the present invention can separate and identify drug resistant protein of Mycobacterium tuberculosis to provide new way for further understanding the drug resisting mechanism of Mycobacterium tuberculosis, fast clinical detection of drug resistant strain, and developing vaccine and medicine.

The slow released compound antituberculotic preparation contains at least one of rifampicin, pyrazinamide, kanamycin, isoniazide, rifapentine, etc. The slow released preparation is slow released injection or slow released implanting agent. The slow released injection consists of slow released microsphere and solvent, the slow released microsphere contains slow releasing supplementary material and antituberculotic, and the solvent is special solvent containing suspending agent carboxymethyl cellulose sodium and of viscosity of 100-3000 cp at 20-30 deg.c. The slow releasing supplementary material is EVAc, PLA, PLGA, sebacic acid copolymer, etc. The slow released compound antituberculotic preparation is set or injected into local tuberulosis focus to treat various kinds of intractable tuberulosis, and has medicine releasing period up to 30-40 days, less systemic toxicity and unique curative effect.

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 relates to a bone tissue engineering stent and a preparation method thereof. The bone tissue engineering stent is prepared from PLGA, isoniazide, rifampicin, allogeneic bone power and bone morphogenetic protein at the weight ratio of (87-51) to (1-6) to (1-6) to (10-30) to (1-7); according to the bone tissue engineering stent, polylactic acid-hydroxyacetic acid material, allogeneic bone power, antituberculosis drugs and bone morphogenetic protein are combined by adopting a 3D printing technology, a bioactive stent is manufactured by adopting the 3D printing technology, the physical, chemical and biological properties of the stent are detected, and the bone tissue engineering stent has the good biocompatibility and the good bone-formation promotion capacity and is biodegradable.

The invention relates to an artemisinin pharmaceutical composition, and particularly relates to a composition of nano chitosan artemisinin and antituberculosis drugs, used for treating drug-resistant tuberculosis. The pharmaceutical composition comprises the following effective components: the antituberculosis drugs, the nano chitosan artemisinin, three nano chitosan artemisinin derivatives or artemisinin and a derivative of artemisinin, wherein the nano chitosan artemisinin is prepared from the following ingredients by weight percent: 40-805 of artemisinin or artemisinin derivatives, 1-5% of polyvinyl pyrrolidone and 15-50% of nano chitosan. Artemisinin drugs, the nano chitosan artemisinin and derivatives, and the antituberculosis drugs are used as the pharmaceutical composition, so that drug-resistant tubercle bacillus can be inhibited and killed; and the pharmaceutical composition has a prominent curative effect on the drug-resistant tuberculosis.

The invention relates to benzothiazine-4-ketone compounds (shown in the formula I and formula I' in the description) containing basic nitrogen heterocyclic fragments, preparing methods and medical application of the benzothiazine-4-ketone compounds and antituberculosis drug compositions with the benzothiazine-4-ketone compounds as effective constituents, in particular to a 6-trifluoromethyl-8-nitryl-4H-benzo[e][1,3] thiazine-4-ketone compound. A 2-substituent group is 1-nitrogen heterocyclic alkyl or dinitrogen heterocyclic alkyl. R represents H, an alkyl group of 1-4 C atoms, heterocyclic alkyl of 4-7 C atoms, a phenyl group and a substituted phenyl; R1 represents H, an alkyl group of 1-3 C atoms and heterocyclic alkyl of 3-6 C atoms; R2 represents H, an alkyl group of 1-4 C atoms, heterocyclic alkyl of 4-7 C atoms, a phenyl group and substituted phenyl; n1 represents 0-1; n2 represents 1-3; n3 represents 1 and 3.

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 invention provides a tubercle bacillus drug tolerance detection reagent kit and method. The tubercle bacillus drug tolerance detection reagent kit comprises a tubercle bacillus drug tolerance detection reagent, wherein the tubercle bacillus drug tolerance detection reagent comprises a sequencing primer in accordance with a tubercle bacillus drug tolerance gene; the tubercle bacillus drug tolerance gene comprises one or more genes of rpoB, katG, inhA-promoter, inhA-structural, furA, embB, ubiA, pncA, rpsA, gyrA, gyrB, eis, rpsL, rrs, tlyA, rplC and rrl; and further, the reagent kit also contains a tubercle bacillus nucleic acid detection reagent, and the tubercle bacillus nucleic acid detection reagent comprises a primer pair 1 in accordance with IS6110, a primer pair 2 in accordance with the IS6110 and a probe primer in accordance with the IS6110. Through the adoption of the tubercle bacillus drug tolerance detection reagent kit disclosed by the invention, tubercle bacillus nucleicacid in samples can be quickly detected, and positive samples can be further subjected to drug tolerance detection; and the tubercle bacillus drug tolerance detection reagent kit has good sensitivity, good specificity and good accuracy, and can perform mutation detection on 48 sites of 17 drug tolerance genes of common antituberculosis drugs and fragment deficiency detection of an intergenic region, so that the tuberculosis medication can be more accurately and comprehensively guided.

A pharmaceutical composition for treating tuberculotic diseases with no side effect / low side effect is provided by the present invention, which pharmaceutically effective amount of one or more compounds chosen from isoniazid, rifampin, pyrazinamide and ethambutol, and pharmaceutically effective amount of substances which can reduce the side effect of the antituberculosis agents.

The invention belongs to the field of traditional Chinese medicines, and relates to dicliptera chinensis polysaccharide extracted and purified by using dicliptera chinensis whole herb as a raw material and application of the dicliptera chinensis polysaccharide in preparation of medicines for treating liver injury caused by antituberculosis drugs. The present invention discloses a preparation method of the dicliptera chinensis polysaccharide, and animal experiments prove that the dicliptera chinensis polysaccharide has very good effect on treatment of drug-induced liver injury in mice caused by combined use of antituberculosis drugs isoniazide and rifampicin. The dicliptera chinensis polysaccharide can be applied not only to chemical liver injury, and also has specific effects on tuberculosis drug-induced liver injury; the new application opens up a new area for medicinal value of the dicliptera chinensis polysaccharide, and the dicliptera chinensis polysaccharide has important application value and economic benefit.

The invention discloses a benzothiazinone compound and a preparation method and application of the benzothiazinone compound as an antituberculosis drug, and particularly relates to a novel compound with a benzothiazinone skeleton. The compound has an inhibition effect on tubercle bacillus, especially tubercle bacillus with clinical drug resistance. Results show that the compound shows an obvious antibacterial effect, the antibacterial effect far exceeds that of a positive control isoniazide, and particularly, compared with a positive control pBTZ169, the compound has an obvious and good cLogPvalue.

The invention relates to a preparation method of a diphasic quick differential medium of mycobacterium tuberculosis, a method for quickly differentiating the mycobacterium tuberculosis by using the medium, a method for testing the drug resistance on antituberculous drugs caused by the mycobacterium tuberculosis and a method for quickly culturing a bacillus Calmette and Guerin vaccine by using a liquid medium in the medium. The diphasic medium prepared by adopting the method can be used for quickly culturing the mycobacterium tuberculosis, the diphasic quick culture medium is capable of differentiating the mycobacterium tuberculosis within 2-5 days, the differentiated mycobacterium tuberculosis can be subjected to drug resistance detection of the antituberculous drugs such as rifampicin, isoniazide and streptomycin by virtue of a reverse transcription PCR (polymerase chain reaction) method, and the liquid medium prepared by adopting the method is capable of finishing the culture of the bacillus Calmette and Guerin vaccine within 6-9 days.

The invention relates to the field of pharmaceutical chemistry and specifically relates to oridonin and an ent-6, 7-ring opening kaurene type derivative thereof. The invention discloses oridonin derivatives and use of the oridonin derivatives in preparing antituberculosis drugs.

The invention belongs to the field of molecular biology of screening novel antituberculosis drugs target, vaccinum antigen and testing novel markers. The invention provides a method for screening the protein of Bacillus tuberculosis rifampicine-resistant: First, cultivating multi-drug-resistant strains; Secondly, separating the were isolated strains of multi-drug-resistant and sensitive strains of multi drug-resistant strains and protein from sensitive strains separately; Thirdly, determining the multi-drug-resistant protein by comparing the proteins of multi-drug-resistant strains and sensitive strains; Finally, separating and identifying the multi-drug-resistant protein. This invention provides a method which can accurately separate and identify multi-drug-resistant protein of Bacillus tuberculosis. The invention provides novel way for better understand of the multi-drug-resistant mechanism of Bacillus tuberculosis, rapid detecting of clinical multi-drug-resistant strains and the development of vaccine and drug target.

The invention discloses a method for simultaneously determining blood concentrations of six first-line antituberculosis drugs and antifungal drugs voriconazole in blood plasma, and relates to the technical field of clinical blood concentration monitoring and control. According to the method, an HPLC MS / MS method is adopted, acetaminophen is used as an internal standard, the blood plasma is subjected to protein precipitation through using methyl alcohol, is subjected to elution and separation through HPLC under the specific gradient elution condition according to a specific mobile phase, then enters a mass spectrum system and undergoes multi-reaction monitoring and analysis, therefore, accurate quantification of the blood concentration of seven antibiotics is achieved at the same time. Themethod has the advantages of strong specificity, high sensitivity, good precision and accuracy, good stability, high extraction recovery rate, no obvious matrix effect, simple operation, convenience and rapidness. The method provided by the invention can realize high-throughput determination of clinical samples of tuberculosis patients and guide clinical individualized medication.

The invention relates to a bone tuberculosis medicine controlled-release microsphere with a bone repairing function and a preparation method. According to structural design, an active component for inducing bone growth is put into the microsphere, a hydrophobic drug, namely rifampicin, which takes functions into play in a later bacterium inhibition period, is supported by a middle polylactic acidlayer, a hydrophilic antituberculosis drug, namely isoniazide, is coated by chitosan and is arranged in an outer layer, and sequential layer-by-layer release of the three components can be achieved. After step-by-step bacterium inhibition of the medicines, the active component for inducing bone growth is released, then bone repairing can be achieved, and bone tuberculosis can be treated comprehensively. Carrier components are also finely selected, phosphorus, calcium, collagen and the like are all essential substances for osteogenesis, and the chitosan and the polylactic acid are good in biocompatibility and can be degraded and absorbed at focuses. Therefore, the controlled-release microsphere has very good specificity, is capable of providing an efficient novel material to clinical treatment on bone tuberculosis, and has great application potential and values.

The invention discloses a benzothiazinone compound, a preparation method thereof and an application of the benzothiazinone compound as an antituberculosis drug, and particularly relates to a novel compound with a benzothiazinone skeleton. The compound has an inhibition effect on tubercle bacillus, especially tubercle bacillus with clinical drug resistance. Results show that the compound shows an obvious antibacterial effect, the antibacterial effect far exceeds that of a positive control isoniazide, and particularly, compared with a positive control pBTZ169, the compound has an obviously goodcLogP value.

This invention relates to compounds and an application of the compounds in preparation of an antituberculosis drug. The compounds have structures represented by a formula I or a formula II shown in the description, and the compounds represented by the formula I or the formula II can be prepared by performing fermentation culture on amycolatopsis methanolica MS100137. Another purpose of the invention is to provide the application of the compounds represented by the above formula I and formula II in the preparation of the antituberculosis drug. The compounds provided by the invention are obtained by a fermentation culture product of the amycolatopsis methanolica separated from an ocean, and have anti-BCG activity; the obtained compounds have important theoretical significance and practical application value; and the compounds have great significance to health cause of humans.

The invention provides a porous calcium phosphate support loaded microsphere composite material, as well as a preparation method and application thereof. The porous calcium phosphate support loaded microsphere composite material comprises a porous calcium phosphate support, wherein a polylactic acid-glycolic acid copolymer microsphere is loaded in each hole of the porous calcium phosphate supportand the polylactic acid-glycolic acid copolymer microsphere coats one or more antituberculosis drugs. The experiment proves that the porous calcium phosphate support loaded microsphere composite material has a filling bone remodeling and bone inducing osteogenesis function, further has an effect of locally continuously and three-dimensionally slowly releasing the antituberculosis drugs, and achieves an effect of treating osteoarticular tuberculosis and reducing recurrence. The invention further provides the preparation method and the application of the porous calcium phosphate support loaded microsphere composite material.

The invention discloses Chinese compound preparation for treating liver injury and a preparation process thereof. The preparation is prepared from the following raw materials in part by weight: 10 to 20 parts of oriental wormwood, 10 to 20 parts of pericarpium citri reticulatae viride, 5 to 15 parts of medlar, 5 to 15 parts of raw rehmannia glutinosa, 5 to 15 parts of Codonopsis pilosula, 5 to 15 parts of glossy privet fruit and 5 to 15 parts of Schisandra chinensis. The oriental wormwood having the effects of eliminating dampness, soothing liver and gall and promoting dieresis is used as a monarch medicine; pericarpium citri reticulatae virid is mainly used for relieving stagnant Qi and eliminating liver stagnation and is used as a minister medicine; the medlar and glossy privet fruit are used as assistant medicines for nourishing liver and tonifying kidney; and the medicines are combined to produce effects of protecting liver, removing jaundice, and tonifying liver and kidney and has remarkable effect on costalgia due to liver injury, jaundice and liver-qi depression, which are caused by antitubercular agents. The Chinese medicinal composition for treating liver injury, which is prepared by the invention, is simple process control, high in bioavailability, good in medicine effect, quick in treatment effect and low in cost.

The invention discloses a method for detecting an anti-tuberculosis drug in serum by an ultra-high performance liquid chromatography-tandem mass spectrometry technology. The antitubercular drug comprises cycloserine (CYS), pyrazinamide (PZN), isoniazid (INZ), p-aminosalicylic acid (P-ASA), ethiisonicotinamide (ETN), ethambutol (ETB), clofazimine (CFM), bedaquiline (BDQ), rifampicin (RFP), rifbutine (RFB) and rifapentine (RFT). The method includes: detecting the content of the antituberculosis drug in the pretreated serum by adopting an ultra-high performance liquid chromatography-tandem mass spectrometry method, performing quantifying by utilizing a mass spectrometry isotope internal standard method, establishing a calibration curve by taking the concentration ratio of the standard substance to the internal standard substance as an X axis and the peak area ratio of the standard substance to the internal standard substance as a Y axis, and calculating the concentration of the target drug in the serum; the method is high in sensitivity, strong in specificity and simple in pretreatment process, separation and detection of the anti-tuberculosis drugs in serum are completed within 5 min, and a simple and rapid detection method is provided for clinical concentration monitoring of the anti-tuberculosis drugs.

The slow released compound antituberculotic preparation containing synergist is implanting agent or slow released injection comprising slow released microsphere and solvent. The slow released microsphere consists of slow releasing supplementary material, at least one antituberculotic selected from rifampicin, isoniazid and pyrazinamide and at least one antituberculotic synergist selected from cycloserine, ofloxacin, ciprofloxacin, sparfloxacin and capreomycin. The solvent is special solvent containing suspending agent carboxymethyl cellulose, etc. and with viscosity of 100-3000 cp at 20-30 deg.c. The slow releasing supplementary material is selected from EVAc, PLA, PLGA, etc. The slow released compound antituberculotic preparation can release antituberculotic in the local tubercolosis part for 30-40 days so as to maintain the local effective medicine concentration while lowering systemic toxicity. The present invention has obvious unique treating effect on various kinds of intractable tuberulosis.

The invention discloses a benzothiazinone derivative, a preparation method thereof and application of the benzothiazinone derivative as an antituberculosis drug, which relate to a novel compound witha benzothiazinone skeleton. The compound has an inhibition effect on tubercle bacillus, particularly tubercle bacillus with clinical drug resistance. The benzothiazinone skeleton benzene ring is creatively changed, especially the substituent group is creatively changed to obtain a series of compounds, and an unexpected technical effect is achieved; the compound disclosed by the invention has an excellent inhibition effect on tubercle bacillus; compared with the existing clinical first-line drug isoniazide (MIC 0.5 muM), the reported compound activity has very great advantages, and more importantly, compared with the benzothiazinone antituberculosis drug pBTZ 169 in the existing research stage, the compound provided by the invention has a lower cLogP value and better druggability.

The invention relates to a vascular targeting embolism sustained release agent of a triple compound microsphere for an antituberculosis drug, a preparation method and applications thereof. The sustained release agent comprises a carrier and a drug, wherein the drug is encapsulated by the carrier, the carrier is selected from sodium alginate or chitosan, and the drug is a triple compound antituberculosis drug which comprises rifampin, isoniazide and pyrazinamide or moxifloxacin. Three antituberculosis drugs are employed as matrixes of a drug solution, sodium alginate or chitosan is used as a carrier solution, and a prepared solution is obtained by mixing the drug solution and the carrier solution. A polymer solution having the drug is enabled to be dispersed into droplets with certain particle sizes and to be sprayed into a curing liquid through a method of high voltage electrostatic droplets, and thus the microsphere for the antituberculosis drug are prepared in the presence of calcium ions. The embolism sustained release agent can be used in the drug for treating pulmonary tuberculosis, pulmonary tuberculosis massive hemoptysis, cavitary pulmonary tuberculosis, renal tuberculosis, osteoarticular tuberculosis, genital tubercolosis, thyroid tuberculosis, tuberculosis of cervical lymph nodes, pericardial tuberculosis, chest-wall tuberculosis and other in-vivo tuberculosises.

The invention relates to an antitubercular pharmaceutical composition containing balloonflower root extract, which is prepared from the components of 0.1-100 parts of balloonflower root extract by weight and 1 part of antitubercular drug by weight through the steps as follows: extracting the balloonflower root extract for three times by water or extracting the balloonflower root extract for three times by 40-95% ethanol at the temperature of 90 DEG C, and concentrating, wherein the weight measurement ratio of the balloonflower root extract to the water is 1:(6-10), and the weight measurement ratio of the balloonflower root extract to the ethanol is 1:(5-15). The pharmaceutical composition in the invention has the functions of enriching the antitubercular drugs in lung tissues and improving the potency of the antitubercular drugs for curing phthisis as compared with single antitubercular drugs, and simultaneously has the positive effects such as reducing the liver injury caused by the antitubercular drugs and the like. By utilizing he pharmaceutical composition, the phthisis therapeutic window of the antitubercular drugs can be amplified, and the capability of effectively killing tubercle bacillus is enhanced, thereby increasing the potency, shortening the treatment cycle and lowering the possibility of tolerance of tubercle bacillus.

The invention relates to an antituberculosis drug disclosed as Formula I and a screening method thereof. An antituberculosis drug screening model is established by using alanine racemase as a target spot; and the model is utilized to screen out the antituberculosis drug with application prospects. The invention also relates to a composition containing the antituberculosis drug disclosed as Formula I and application of the antituberculosis drug disclosed as Formula I in preparing drugs for preventing or treating tuberculosis.