141 results about "Isoniazid" patented technology

The present invention relates to molecular biology, microbiology, and medicine and provides the method for detection of Mycobacterium tuberculosis complex with simultaneous evaluation of sensitivity of the strains to rifampicin and isoniazid in clinical sample on differentiating biochip. The method is based on two-stage multiplex PCR to obtain fluorescent DNA fragments followed by hybridization of these fragments on microarray containing the set of specific discriminating oligonucleotides. The determination of the resistance of Mycobacterium tuberculosis to rifampicin and isoniazid is carried out by evaluation of point nucleotide substitutions in DNA of microorganism. The present invention allows conduct analysis directly in clinical sample, to evaluate a number of mutations simultaneously, to decrease the cost price of analysis, and to reduce the time of its conducting. The present invention also relates to set of primers, biochip, and set of oligonucleotide probes used in realization of the method.

The invention discloses a chirality 7-(piperazine-substituted pyrazol aldehyde condensation isoniazide) fluoroquinolone carboxylic acid derivative as well as a preparation method and application thereof. The chirality 7-(piperazine-substituted pyrazol aldehyde condensation isoniazide) fluoroquinolone carboxylic acid derivative is a compound with the general structural formula (I), wherein R1 is H, methyl or ethyl, and R2 is H or methyl. According to the chirality 7-(piperazine-substituted pyrazol aldehyde condensation isoniazide) fluoroquinolone carboxylic acid derivative provided by the invention, fluoroquinolone, isoniazide and pyrazole aldehyde hydrazone are effectively combined to form a compound with a new structure; superposition and cooperation of activity are achieved; superposition of the three pharmacophores of fluoroquinolone, isoniazide and pyrazole aldehyde hydrazone is realized, the antituberculosis activity is improved, the toxic and side effects of fluoroquinolone and isoniazide to normal cells are decreased, and meanwhile, the probability that mycobacterium tuberculosis resists such drugs can be lowered; the chirality 7-(piperazine-substituted pyrazol aldehyde condensation isoniazide) fluoroquinolone carboxylic acid derivative can serve as an antituberculous active substance used for development of an antituberculous drug with a new structure.

The invention provides a medicament for treating pulmonary tuberculosis. Adenophora root, Tuber of Dwarf Lilyturf, asparagi radix, rehmanniae radix, Rehmannia Glutinosa, stemona, tendril-leaved fritillary bulb, donkey-hide gelatin, pseudo-ginseng, Poria cocos, Chinese yam, polyghace seche, lily, bletilla striata, hairyvein agrimony, cortex lycii, isoniazid and vitamin B6 are mixed uniformly, and crushed into a medicinal powder of 80-120 mesh; and the medicinal powder is disinfected and filled into capsules to obtain the capsule product. The medicament is composed of traditional Chinese medicines and Western medicines, has efficacies of resisting tuberculosis, disinfesting, supporting right, securing the root, nourishing yin, reliving cough, reducing phlegm and stopping bleeding, and can play fast curative effect without side effect on treatment of pulmonary tuberculosis.

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.

PCT No. PCT / RU97 / 00098 Sec. 371 Date Mar. 17, 1998 Sec. 102(e) Date Mar. 17, 1998 PCT Filed Apr. 2, 1997 PCT Pub. No. WO98 / 43982 PCT Pub. Date Aug. 10, 1998Biologically active substance on the basis of tetracyclicnitrogen heterocycles of pyrimidine row for treating tuberculosis, mycobacteriousis, viral diseases, infections caused by chlamydias, and also diseases which are accompanied by immunodeficiency, in particular malignant neoplasm, has high antimicrobial activity, in particular to strains of mycobacteria which are resistant to the prototype-isoniazid, and simultaneously possess antiviral activity (relative to herpes simplex viruses), antichylamidial activity and also stimulate production of endogenic interferons in organisms. It represents a derivative of 5-oxo-5H-[1]-benzopyrano-[5,6-b]-4-oxo-4H-[1,2]-pyrimido-1,4,5,6-tetrahydro-1,3-thiazine (1) of general formula(1). (I-X) where: R1-H or halogen; R2-H, or halogen, or nitro-group, or hydroxy-group or methoxy-group.

This invention relates to a test for detecting a Mycobacterium tuberculosis (tuberculosis or TB) infection in a patient or subject, specifically a diagnostic test, including a breath test, whereby patients are provided a small dose of an isotopically labeled TB drug, Isoniazid (INH) orally or directly to the lungs of the patient or subject. If TB is present, a TB enzyme mycobacterial peroxidase KatG oxidizes the INH; and KatG specific metabolites, in particular, isotopically labeled nitric oxide (NO), nitrites, nitrates, carbon monoxide (CO) or carbon dioxide converted from carbon monoxide of INH cleavage are measured. Other embodiments relate to a diagnostic breath test for detecting TB utilizing isotopically labeled urea (preferably, carbon-13 labeled urea), alone or in combination with isotopically labeled isoniazid (preferably, nitrogen-15 labeled isoniazid), wherein M. tuberculosis organism, if present in the patient or subject's lungs (or other tissues), will metabolize the isotopically labeled urea to isotopically labeled carbon dioxide (CO2) such that a determination of the residence of M. tuberculosis, including residence of an isoniazid resistant strain of M. tuberculosis, may be made.

The invention discloses a fluoroquinolone acetal ftivazide. According to the fluoroquinolone acetal ftivazide, fluoroquinolone aldehyde and isoniazide are combined to form a hydrazones compound which has a chemical structure shown as the following chemical structural formula in the specification. The fluoroquinolone acetal ftivazide achieves the parataxis of fluoroquinolone and isoniazide antituberculous medicines, and reduces the toxic and side effects of the two, and reduces the probability of the generation of the resistance of mycobacterium tuberculosis to an antibacterial agent with double effects; and the fluoroquinolone can be used as a medicine active substance to develop a mycobacterium tuberculosis medicine with a brand new structure.

The present invention relates to molecular biology, microbiology and medicine, and provides a method for detecting nodule offshoot bacilli complex body in clinic samples and evaluating the sensitivity of strain to rifampicin as well as isoniazid in distinguish biochip. The method obtains fluorescence DNA segments based on two-step multiple PCR, then to hybridize said segments on a micro-array containing differential distinguished oligonucleotide group. To determine the resistance of concretion offshoot bacilli to rifampicin and isoniazid by means of evaluating point nucleotide replacement in microbiology DNA. The present invention allows analyze directly clinic sample to evaluate mass mutation at one time, so as to reduce analysis cost and implement time. The present invention also relates to primer group, biochip and oligonucleotide probe group for implementing said method.

The present invention belongs to the field of chemically synthesized medicine and its preparation process. The medicine of the present invention is synthesized with amantadine, moroxydine, 5-Fu (5-Fc), isoniazid and other clinical medicine and polyoxometallate, and through self-assembling. The said polyoxometallate includes heteropoly acid salts of Keggin type with chemical expression XM12O40n-, Dowson type X2M18O62n- and of chemical expression LnW10O36n-. The combined use of said medicines and polyoxometallate has obvious curative effect on intractable streptococcus pneumoniae infection.

A compound of the general Structure (VII) or (VIII) including isoteres and pharmaceutically acceptable salts thereof, wherein R1, R2 (where X=—CONR6—), R3 and R7 are the same or different and each represents an amino-acid side chain moiety; R2 (where X=—CHZ—), R4 and R6 are the same or different and each represents hydrogen, C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl; K represents a linear or branched chain of carbon atoms and containing 1-10 atoms; L represents a moiety capable of chelating zinc in the active site of a histone deacetylase (HDAC) or of conversion to such a moiety in vivo (by hydrolysis or reduction, for example); M is a linear or branched chain of carbon or other atoms and containing 1-10 atoms, and capable of undergoing in vivo cleavage to give Structure (VII); and Z is a heteroatom bonded to the macrocycle by a single or double bond, and any other group bonded to Z is H or a protecting group.

This invention relates to a test for detecting a Mycobacterium tuberculosis (tuberculosis or TB) infection in a patient or subject, specifically a diagnostic test, including a breath test, whereby patients are provided a small dose of an isotopically labeled TB drug, Isoniazid (INH) orally or directly to the lungs of the patient or subject. If TB is present, a TB enzyme mycobacterial peroxidase KatG oxidizes the INH; and KatG specific metabolites, in particular, isotopically labeled nitric oxide (NO), nitrites, nitrates, carbon monoxide (CO) or carbon dioxide converted from carbon monoxide of INH cleavage are measured. Other embodiments relate to a diagnostic breath test for detecting TB utilizing isotopically labeled urea (preferably, carbon-13 labeled urea), alone or in combination with isotopically labeled isoniazid (preferably, nitrogen-15 labeled isoniazid), wherein M. tuberculosis organism, if present in the patient or subject's lungs (or other tissues), will metabolize the isotopically labeled urea to isotopically labeled carbon dioxide (CO2) such that a determination of the residence of M. tuberculosis, including residence of an isoniazid resistant strain of M. tuberculosis, may be made.

The invention discloses a topiroxostat impurity synthesis method, and belongs to the chemical pharmaceutical technical field. The method comprises the steps: with methyl isonicotinic acid-N-oxide (2) as a starting material, generating 2-cyano-4-pyridine carboxylic acid methyl ester from methyl isonicotinic acid-N-oxide (2) and trimethylsilyl cyanide; carrying out hydrazinolysis of the compound (3) to generate 2-cyano-isoniazid (4); and carrying out ring self-formation of the compound (4) to generate a target 2-(3-(2-amino pyridine-4-yl)-1H-1,2,4-triazole-5-yl)isoniazide (1). The synthesized high-purity topiroxostat impurity can be used as an impurity standard in topiroxostat finished product detection analysis, so as to enhance accurate positioning and qualitation on the impurity in the topiroxostat finished product detection analysis, be conducive to strengthening of the control of the impurity, and improve the quality of the topiroxostat finished product; the method provided by the invention has the advantages of cheap and easily obtained raw materials, and simple operation; the yield of the obtained product is 85%+ / -5%, and the HPLC purity is not less than 98%.

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.

The invention discloses a preparation method of isoniazid. The method comprises the following steps: 1) performing esterification reaction to isonicotinic acid, alcohol and acylating reagent to obtain isonicotinic acid ester; 2) performing condensation reaction to isonicotinic acid ester and hydrazine hydrate and performing post-treatment to reaction liquid to obtain isoniazid finished products. The isoniazid is prepared firstly through esterification of isonicotinic acid and alcohol and then condensation of the obtained ester and hydrazine hydrate. The method can well control the content of impurities in the target product isoniazid, high-purity isoniazid can be obtained, the purity is above 99.9 percent and the content of individual impurity is smaller than 0.10 percent. The method is simple to operate, is easy to control and is applicable to industrial operation. In addition, by using recovered isonicotinic acid to prepare isoniazid, the cyclic utilization of resources can be realized, the waste emission is reduced, the cost is reduced and the method is very suitable for industrial production.

The invention discloses a preparation method of isoniazid para-aminosalicylate. The preparation method comprises that a sodium para-aminosalicylate solution is added with an acid and then is extracted by an organic solvent and isoniazid is added into the extract to produce a desired product. The isoniazid para-aminosalicylate product prepared by the preparation method has isoniazid para-aminosalicylate purity above 98%. Through the preparation method, a yield of 90 to 98% is obtained. The preparation method adopts simple and environmentally friendly processes, realizes recycle of an extraction solvent and saves greatly costs.

The invention discloses a mycobacterium tuberculosis drug-resistant mutant gene detection kit comprising: (1) a gene chip which has (i) a nucleotide probe, wherein the probe is a sequence of SEQIDNos: 1-31 or a complementary sequence of SEQIDNos: 1-31, (ii) a DNA sequence labeled with biotin points, wherein the sequence is SEQIDNO. 32, (iii) an IS6110DNA sequence of a mycobacterium tuberculosis complex, wherein the sequence is SEQIDNo. 33; (2) various primers used for amplifying DNA sequences in clinical samples, wherein the DNA sequences of the primers are SEQIDNos. 34-41. The kit of the invention detects the drug resistance of mycobacterium tuberculosis to rifampin and isoniazid, provides reference basis for the prevention and treatment of tuberculosis, and has significant meaning.

The invention relates to a medicament for treating pulmonary tuberculosis by combined chemotherapy with traditional Chinese medicine Fuying and a preparation method; in the medicament, a traditional Chinese medicine of Fuying No. I comprises gecko, donkey-hide gelatin, stemona, adenophora stricta, radix ophiopogonis, prunella vulgaris, radix scrophulariae, fritillaria thun-bergli, cortex lycii radicis, bletilla striata, picrorhiza scrophulariiflora pennell, rehmanniae radix, and anemarrhena, and is mainly used for expelling evil and nourishing yang; a traditional Chinese medicine of Fuying No. II comprises codonopsis pilosula, Chinese yam, poria cocos, schisandra chinensis, radix rehmanniae preparata, angelica, caulis spatholobi, gentrin knotweed, bighead atractylodes rhizome, and radix astragali, and is mainly used for strengthening the body resistance and nourishing body; western medicines participating the combined chemotherapy comprise: streptomycin injections, isoniazid tablets, rifampin, and pyrazinamide capsules; during the combined chemotherapy with the medicines, not only stable therapeutic effect on pulmonary tuberculosis is realized, but also nourishing treatment effect on patients with hepatopathy is realized; during preparation, geckoes are grinded into fine powder, and fried with donkey-hide gelatin; then the other medicines are cleaned, dried, pulverized, and grinded into fine powder; the fine powder is sieved by a No. 6 sieve to obtain a pulvis; the pulvis is packaged into bags to obtain the Fuying No. I. During the preparation of the Fuying No. II, the medicines are also selected, cleaned, pulverized, and grinded into fine powder; the fine powder is sieved by a No. 6 sieve to obtain a pulvis; the pulvis is packaged into bags to obtain the Fuying No. II. During treatment, the traditional Chinese medicine Fuying is combined with western medicines for administration.

The present invention uses water or low-grade alcohol with a certain concentration as solvent, dissolves the isoniazid in the above-mentioned solvent, then adds the p-aminosalicylic acid, and adopts the processes of heating, stirring, cooling and separation so as to obtain the invented product pasiniazide.

The invention relates to compound rifampin capsules and a preparation method thereof, rifampin and isoniazide are separately made into coated micro-pellets; with selective use of an enteric-coating material and a gastric-coating material, the drug has good release performance in vivo, a contact reaction between rifampin and isoniazide is effectively prevented, the drug stability and the pharmacological effect of drug compound use are improved, the ideal drug therapeutic effect is achieved, and the preparation method is simple and feasible and is easy to popularize.

The present invention provides an anti-tuberculosis gel preparation, which belongs to the technical field of ultrasonic therapy. The anti-tuberculosis gel preparation comprises, on the basis of dosage percentage, 0.5 to 8% of hydrophilic polymer materials, 0.5 to 15% of penetration enhancers, 2 to 10% of humectants, 0.5 to 3% of isoniazid, 2 to 5% of rifamycin and water. The preparation method for the gel preparation comprises the following steps: 1, preparing the components of gel preparation in proportion; 2, immersing the hydrophilic polymer materials in water to dissolve the materials; 3, adding the penetration enhancers and humectants into the obtained solution and carrying out stirring until the penetration enhancers and humectants dissolve; 4, adding isoniazid and rifamycin into the solution and carrying out uniform mixing under stirring. When used for ultrasonic medicine phoresis therapy, the gel preparation can guarantee that carried drug components smoothly penetrate into bodies to exert pharmacological effects and treat tuberculosis, besides exerting an effect of ultrasonic coupling.

The invention provides a method for detecting isoniazid drug resistance of mycobacterium tuberculosis by using a pyrosequencing technology. The method comprises: step 1, performing a PCR amplification for a KatG gene, step 2, performing the pyrosequencing of the PCR amplification products and determining whether or not the KatG gene has mutation points, wherein the pyrosequencing uses a SNP mode, and a nucleotide sampling sequence is GTCACAGTCTG. The method for detecting the isoniazid drug resistance of the mycobacterium tuberculosis by using the pyrosequencing technology can directly detect drug resistance from phlegm samples of patients, do not need to isolate and culture M. tuberculosis strains, and thus, compared with present detection methods, can shorten detection time, and reduce reaction times and amounts of detecting reagents required by the pyrosequencing.

The invention discloses magnetic-targeted isoniazid composite drug carrying microspheres and a preparation method thereof. The composite drug carrying microspheres comprise the following components: 1-89% of magnetic Fe3O4, 1-80% of isoniazid and 10-19% of chitosan. The preparation method comprises the following steps: (1) preparing the magnetic Fe3O4, namely dissolving a Fe<3+>-containing compound and a Fe<2+>-containing compound in water, introducing inert gas, adding an alkali solution and stirring at a certain temperature to obtain the magnetic Fe3O4; and (2) preparing the composite drug carrying microspheres, namely adding the Fe3O4 and the isoniazid into an acid solution of the chitosan, dripping a sodium tripolyphosphate solution at a certain temperature, and carrying out magnetic separation and freeze drying to obtain the magnetic-targeted isoniazid composite drug carrying microspheres. The magnetic-targeted isoniazid composite drug carrying microspheres disclosed by the invention have the advantages of superparamagnetism, small particle size, dispersion uniformity, good biocompatibility and the like and can be used for magnetic-guided passive targeting therapy.

The invention is a divisional application of 200610113436.7. The invention discloses novel purpose of isoniazid shown as a formula (I) as histone deacetylases inhibitor and application of isoniazid to preparation of medicaments for preventing and / or treating a plurality of diseases correlative to histone deacetylases.

The invention relates to a dry powder inhalant capable of preventing mycobacterium tuberculosis from transmitting through respiratory tract, and is capable of effectively solving a medical problem that mycobacterium tuberculosis infects pulmonary tuberculosis through the respiratory tract. The method comprises the following steps of: preparing the dry powder inhalant from 9.9-80% of an isoniazide sustained release microsphere, 19.9-90% of a rifampicin sustained release microsphere and 0.1-5% of a flow aid by weight percent, uniformly mixing the isoniazide sustained release microsphere, the rifampicin sustained release microsphere and the flow aid, packaging in gelatin or plastic capsules or aluminum-plastic bubble caps, or packaging in a multi-dosage dry powder inhalation device in the form of a reservoir, so as to obtain the dry powder inhalant. The dry powder inhalant disclosed by the invention is scientific and rational in formula, easy to produce and manufacture, good in use effect, and favorable for the powder to enter into pulmonary alveoli; the medicine is transmitted to and absorbed by the pulmonary alveoli to effectively kill and inhibit mycobacterium tuberculosis in trachea, bronchia and alveoli secretion of the respiratory tract, so as to reduce the quantity of floating droplets of patients of pulmonary tuberculosis removed in the surrounding environment, and to block the transmission of the mycobacterium tuberculosis in the public environment; and therefore, the dry powder inhalant has an important meaning for preventing the pulmonary tuberculosis.

The invention involves a drug combinations including rifampin and isoniazid, the combination contains pH modifier of 0.1% ~ 10% (w / w). Said pH regulator is selected from weak acid- weak acid salt buffer system, weak alkali- weak alkali salt buffer system or weak acid salt- weak alkali salt buffer system. The drug combination in the invention can effectively reduce the product of polymer-3-formyl rifamycin SV isoniazone caused by rifampin and isoniazid degradation, and increased drug stability. The method of the invention has advantages as: operation is convenient, process is simple, equipment needs not improvment and the cost is low.

The invention relates to a preparation method of isoniazid para-aminosalicylate. The preparation method of isoniazid para-aminosalicylate comprises the following steps: (1) respectively weighting water and an organic solvent, mixing, adding para-aminosalicylic acid and isoniazid to a solvent of the water and the organic solvent, heating and stirring; (2) cooling and growing grains, and filtering to obtain isoniazid para-aminosalicylate, wherein the organic solvent is an organic ester with the carbon number of less than or equal to 6. By using the preparation method, the preparation of isoniazid para-aminosalicylate is realized at low cost and high efficiency in a water and ester two-phase solvent system under a simple, convenient and feasible technological condition. The content of isoniazid para-aminosalicylate prepared by the method is higher than 99%. Isoniazid para-aminosalicylate has good appearance crystal form, standard color and luster and good stability. The preparation method has the advantages of few reaction operating units, simple technological process, short time consumption, low production cost, environmental friendliness, simple operation and easiness for control on the implementation process and is suitable for the industrial production of isoniazid para-aminosalicylate.

The invention discloses a method for manufacturing a medicinal paper towel. According to the method, large roll toilet paper is produced by adopting the conventional papermaking process, and liquid medicament spraying, back rolling, cutting, folding or small roll sealed packing are performed. The method is characterized in that the liquid medicament is prepared by dissolving 1-2 parts of amantadine, 1-2 parts of vitamin C, 1-2 parts of moroxydine, 1-2 parts of chlorpheniramine maleate, 1-2 parts of isoniazid, 0.1-0.2 part of protease, 0.1-0.5 part of amylase and 1-2 parts of polyvinyl alcohol into 100 parts of water; and 3-5g of liquid medicament is added into 100g of paper by spraying. The paper towel is soft, and has high toughness; and the medicinal paper towel contains an anti-influenza-virus medicament, so that the medicinal paper towel can be taken as an anti-cold health-care paper towel.

The invention relates to an isoniazid dry powder inhalant for treating pulmonary tuberculosis. The isoniazid dry powder inhalant comprises isoniazid micro-powder and comprises or does not comprise carrier micro-powder; the particle size of the isoniazid micro-powder is treated to 0.1-10 mu m by a fluidized bed supersonic jet milling method or a spray drying method; preferably, auxiliary materialsincluding leucine, mannitol or phospholipid are added into the dry powder inhalant so as to enhance the pelletizing rate of particles; and furthermore, auxiliary materials including magnesium stearate, mannitol, leucine and / or lactose are added so as to improve the flowability of the medicine and reduce the particle agglomeration phenomenon. The preparation process of the isoniazid dry powder inhalant is simple; and the isoniazid dry powder inhalant with relatively high stability can be prepared. The dry powder inhalant can effectively deliver drugs to pulmonary alveoli so as to effectively kill and inhibit tubercle bacillus in respiratory tracts, and is particularly suitable for treating pulmonary tuberculosis patients with impaired liver functions.

The invention relates to a compound antituberculous coating core tablet and a preparing method, and is characterized by improving bioavailability, overcoming drug-resistance and being convenient to take by patients. The compound antituberculous double-release preparation is designed and developed according to the optimum absorbing parts of rifampicin and isoniazide and interaction of the two, the isoniazide and excipient are tabletted in a wet granulation mode and are subjected to enteric coating to be taken as a tablet core, the rifampicin(or the rifampicin and ethambutol hydrochloride, or rifampicin, ethambutol hydrochloride and pyrazinamide) is used as the internal layer which is subjected to dry granulation with the excipient and then is pressed into the compound antituberculous coating core tablet with isoniazide enteric-coated tablet core, so that isoniazide can be released in the small intestine at fixed position, rifampicin can be rapidly disintegrated and released in the stomach, and absorption reduction caused by interaction of rifampicin and isoniazide in the stomach can be effectively avoided. The invention is particularly suitable for being taken by patients suffered from tuberculosis.