20 results about "Isoniazid" patented technology

The present invention discloses a compound with structural formula I. The compound of the present invention exhibits strong inhibitory activity against Mycobacterium tuberculosis, has good antituberculosis effects, and has a significantly reduced MIC value compared with isoniazid, a first-line clinical drug. It has weak inhibitory effects on the proliferation of human hepatoma cells HepG2 and Chang cells and has good safety. In addition, in the experiment of Mycobacterium tuberculosis infection overexpressing DprE1, the antibacterial ability of the compound decreased, further verifying that the compound exerts its antibacterial effect by inhibiting the DprE1 enzyme, and it is a novel DprE1 inhibitor.

The present invention discloses a eutectic mixture of oxaprozin and isoniazid, a pharmaceutical composition, and a preparation method thereof. The eutectic mixture is prepared by a solvent-assisted grinding method and comprises oxaprozin and isoniazid in a molar ratio of 0.1 to 0.9. The oxaprozin + isoniazid eutectic melts at 134±4°C. Compared to oxaprozin and isoniazid alone, the eutectic mixture significantly reduces the melting point and significantly improves the dissolution rate and solubility of oxaprozin, which previously had extremely poor water solubility. The pharmaceutical composition provided by the present invention is easy to industrially produce and apply, and has good application prospects.

The invention provides a method for predicting the dosage of an antituberculous drug, which comprises the following steps of: establishing a group pharmacokinetic model of the antituberculous drug by adopting a nonlinear mixed effect model, a two-atrioventricular model and a mixed residual model through plasma concentration analysis, and calculating the pharmacokinetic parameters of the corresponding model; and the established model is verified based on a graphical method, a visual prediction test method and a nonparametric bootstrap method, and the steps of stability and prediction capability evaluation and the like are completed. According to the anti-tuberculosis drug population pharmacokinetic model established by the invention, individual pharmacokinetic parameters can be estimated, a specific population administration scheme is optimized, the drug curative effect is improved, the adverse reaction risk is reduced, and individualized administration of the anti-tuberculosis drug is realized.

This invention provides a monoclonal antibody 4D5 against Rv0340 that can improve drug resistance in Mycobacterium tuberculosis. The heavy chain variable region of antibody 4D5 has the following amino acid sequences: CDR-H1 (SEQ ID No. 1), CDR-H2 (SEQ ID No. 2), and CDR-H3 (SEQ ID No. 3); and the light chain variable region of anti-Rv0340 monoclonal antibody 4D5 has the following amino acid sequences: CDR-L1 (SEQ ID No. 4), CDR-L2 (SEQ ID No. 5), and CDR-L3 (SEQ ID No. 6). This anti-Rv0340 monoclonal antibody 4D5 was prepared using Rv0340 protein as an antigen, and the effect of the anti-Rv0340 monoclonal antibody on the in vitro growth of Mtb in the presence of anti-tuberculosis drugs was investigated. The results showed that antibody 4D5 could significantly increase the sensitivity of Mtb to isoniazid; and when antibody 4D5 was used in combination with isoniazid, the survival rate of Mtb decreased by 26.58%. This invention provides a new monoclonal antibody drug for specifically improving the sensitivity of Mtb to isoniazid, and has the prospect of application as a monoclonal antibody drug to improve the drug resistance of Mycobacterium tuberculosis.

The invention discloses a method for determining the content of isoniazide (INH) through carbon quantum dots (CQDs), and belongs to the technical field of isoniazide content determination. Fluorescence of the carbon quantum dots is quenched under the oxidation action of potassium permanganate, on the basis of oxidation-reduction reaction, the carbon quantum dots react with isoniazide with reducibility, a fluorescence value is recovered, and quantitative detection is carried out. According to the method, firstly, a standard curve is established according to the linear relation between increase of the fluorescence intensity difference value delta F of a system after isoniazide is added and the concentration of isoniazide, and the content of isoniazide in an isoniazide sheet sample is measured according to the standard curve. The invention provides a simple, convenient, rapid and accurate new method for measuring the content of isoniazide, and also expands the application range of the carbon quantum dots.

The invention discloses a crRNA combination for detecting mycobacterium tuberculosis and a drug-resistant mutation site thereof, a kit and application, and belongs to the technical field of molecular detection. The crRNA combination comprises a crRNA-MTB (Complementary Ribonucleic Acid-Methyl Terminals B) used for detecting the mycobacterium tuberculosis, a crRNA-MTB-rpoB used for detecting the rifampicin drug-resistant mutation site of the mycobacterium tuberculosis, and a crRNA-MTB-katG used for detecting the isoniazide drug-resistant mutation site of the mycobacterium tuberculosis; by designing the specific crRNA combination for detecting the mycobacterium tuberculosis and the drug-resistant mutation site thereof, the sensitivity of detecting the mycobacterium tuberculosis and the drug-resistant mutation site thereof can be remarkably improved, the detection time can be shortened, and synchronous detection of the mycobacterium tuberculosis and the drug-resistant mutation site thereof can be realized, so that the kit has the advantages that the detection sensitivity is greatly improved, and the detection time is shortened. The method has a good application prospect in detection of the mycobacterium tuberculosis and the drug-resistant mutation site of the mycobacterium tuberculosis.

The invention relates to a novel application of piperlongumine in enhancing inhibition of isoniazide on intracellular mycobacterium tuberculosis, piperlongumine can specifically improve the level of ROS (reactive oxygen species) in macrophages infected by mycobacterium tuberculosis, and can enhance autophagy of the macrophages by improving the level of ROS, so that the aim of resisting mycobacterium tuberculosis is fulfilled; piperlongumine combined medication can significantly enhance the inhibition of isoniazid on the growth of mycobacterium tuberculosis in macrophages.

The invention discloses a nucleic acid composition for detecting an isoniazide drug gene based on a nucleic acid mass spectrometry technology, a kit and application thereof, and relates to the technical field of gene detection. The nucleic acid composition disclosed by the invention comprises a multiple amplification nucleotide composition and an extension nucleotide composition, wherein the multiple amplification nucleotide composition is used for carrying out multiple PCR (Polymerase Chain Reaction) amplification on sites of rs1801280, rs1799930, rs1799931, rs1799929, rs1041983 and rs1801279 of an isoniazide drug gene NAT2, and the extension nucleotide composition is used for carrying out a single base extension reaction. By using the nucleotide composition and the kit provided by the invention, the genotype of the 6-site of the isoniazide drug gene NAT2 can be detected by adopting a nucleic acid mass spectrometry technology, and the nucleotide composition and the kit have the characteristics of high sensitivity, good specificity, short detection period and low detection cost. The invention provides a more reliable and low-cost detection kit for detecting related genes of isoniazide medication, and a detection result provides a basis for accurate medication of isoniazide.

The invention discloses a stable isoniazide oral solution. The stable isoniazide oral solution comprises isoniazide, methylparaben, propylparaben, a pH regulator and a solvent. The isoniazide oral solution with good stability is prepared, the absorption and utilization rate of the medicament is improved, and the isoniazide oral solution tastes good and has a good market prospect.

The invention relates to the technical field of biology, and discloses an isoniazid drug resistance related gene Rv2670c of mycobacterium tuberculosis and application of a mutation site of the isoniazid drug resistance related gene Rv2670c. According to the invention, a new gene Rv2670c related to the isoniazide sensitivity change in a mycobacterium tuberculosis genome is found, and a new base mutation site (the 14th base C of the gene Rv2670c is mutated into T) capable of influencing the isoniazide sensitivity of mycobacterium tuberculosis in the mycobacterium tuberculosis genome is verified; the invention provides a novel detection method and a detection technology for judging the drug resistance of mycobacterium tuberculosis to isoniazide, which can be used for preparing tuberculosis diagnostic reagents and designing antituberculosis drugs. The newly found mutation site is combined with the existing product for application, so that the accuracy and the comprehensiveness of the isoniazide drug resistance detection of the mycobacterium tuberculosis are improved.

The present invention provides an application of a polypeptide LLTRAGL in preparing a drug for resisting isoniazid-induced liver damage, belonging to the field of biomedicine technology, and specifically provides an application of a polypeptide in preparing a drug for protecting the liver, wherein the amino acid sequence of the polypeptide is LLTRAGL; and an application of a polypeptide in preparing a drug for resisting isoniazid-induced liver damage, wherein the amino acid sequence of the polypeptide is LLTRAGL. The present invention discovers for the first time that the polypeptide LLTRAGL has a liver-protecting effect, and that the polypeptide LLTRAGL has an anti-INH-induced liver damage activity, providing a new idea for the prevention and treatment of INH-induced liver damage.

The invention discloses a preparation method and application of a BCG (Bacillus Calmette Guerin)-modified polydopamine targeted macrophage nano-system loaded with isoniazide and Mn < 2 + >, and belongs to the technical field of biomedicine. The invention discloses a preparation method of a BCG (bacillus calmette-guerin vaccine) modified polydopamine targeted macrophage nano system loaded with isoniazide and Mn < 2 + >. The preparation method comprises the following steps: preparing MPDA NPs, INH / Mn < 2 + > MPDA NPs and BCG INH / Mn < 2 + > MPDA NPs. According to the invention, a macrophage-targeted BCG modified MPDA NPs drug loading system is used for loading INH and Mn < 2 + >, Mycobacterium tuberculosis (Mtb) is directly killed by INH, a cGAS-STING autophagy pathway is efficiently activated in cooperation with Mn < 2 + > to promote lysosome to digest Mtb phagosome, the problem of immune escape of Mtb is solved, and a theoretical and experimental foundation is laid for developing a new host-oriented tuberculosis treatment technology.

This invention aims to solve the problems of poor flowability of existing nicotinamide mononucleotide (NMN) single material, leading to poor flowability, uneven mixing, and poor content uniformity in NMN formulation preparation. It provides a safe and highly flowable nicotinamide mononucleotide-proline co-crystal. This co-crystal exhibits diffraction peaks at 5.5±0.2° and 16.8±0.2° using Cu-Ka radiation and X-ray powder diffraction at 2θ angles. This co-crystal possesses good bulk density and flowability, allowing for direct tableting or capsule filling of the powder. The product weight variation meets pharmacopoeia requirements, and the process is simple, making it suitable for commercial production. Furthermore, proline, a natural amino acid and a component of collagen, is safer and more reliable as a co-crystal form than isoniazid (classified as a Group 3 carcinogen by the WHO), which is disclosed in existing technologies.

The invention belongs to the field of biological medicine, and particularly relates to application of murrayone or a pharmaceutically acceptable carrier or excipient thereof in preparation of a medicine for preventing and / or treating mycobacterium tuberculosis infection. In-vitro experiments show that murrayone has specific and efficient inhibiting and killing effects on mycobacterium tuberculosis, and has no activity on common gram-positive and gram-negative bacteria. When the murrayone is combined with first-line antituberculosis drugs (such as isoniazide and rifampicin), the drug effects are added. A time killing curve proves that the mycobacterium tuberculosis with high bacterial loading capacity can be completely removed within 48 hours, and the sterilizing effect is lasting. Cell experiments show that the compound has low toxicity to THP-1 human macrophages and good safety, and can effectively kill intracellular infected mycobacterium tuberculosis clinical strains. Therefore, the murrayone can be used as a single drug component or a drug combination component, is used for developing novel, efficient and safe antituberculosis drugs, and is particularly suitable for treating infectious diseases caused by mycobacterium tuberculosis.

The present invention relates to a functionalized manganese-doped mesoporous nanomaterial, its preparation method, and application. The preparation method specifically comprises: preparing solid silica nanospheres; mixing the solid silica nanospheres with maleate and manganese salt aqueous solutions, and preparing manganese-doped mesoporous silica hollow spheres using a hydrothermal method; loading isoniazid and benzothiazole sulfinate into the manganese-doped mesoporous silica hollow spheres to obtain a functionalized manganese-doped mesoporous silica nanomaterial; and compounding the cell membranes of treated mouse breast cancer cells with the functionalized manganese-doped mesoporous silica nanomaterial to obtain a cell membrane-modified functionalized manganese-doped mesoporous silica nanomaterial. Compared with the prior art, the preparation method of the present invention is simple, and the prepared composite nanomaterial has magnetic resonance imaging contrast performance and a good synergistic therapeutic effect. It can be used for magnetic resonance imaging-guided tumor treatment, achieving integrated diagnosis and treatment.

The present invention belongs to the field of organic synthesis technology and specifically provides a photoactive ruthenium complex and a preparation method thereof. The photoactive ruthenium complex provided by the present invention not only decomposes and releases isoniazid under light but also generates singlet oxygen under light excitation, exhibiting dual antibacterial effects, including significant antibacterial effects against Mycobacterium smegmatis, and can be used to treat tuberculosis infection.

The present application relates to the technical field of medicine preparation, more particularly to a kind of isoniazid tablets and preparation method thereof.The weight percentage of the main drug and auxiliary material of the isoniazid tablet is as follows: the main drug is 60% to 80%, the filling agent is 15% to 30%, the binder is 1% to 10%, the disintegrating agent is 1% to 5% and the lubricant is 0.5% to 5%.The present application adopts corn starch as filling agent and binder, pre-gelatinized starch as filling agent, sodium carboxymethyl starch as disintegrating agent to carry out wet granulation process for tablet pressing, adopts oral solid high-density polyethylene bottle for packaging of the preparation, and the related substances of self-made product and reference preparation have no change under the condition of accelerated test for 6 months compared with 0 month.The granules prepared by the present application have uniform particle size, good flowability and compression forming property, low defective rate, excellent tablet core disintegration performance, and the prepared medicine is more stable by adopting oral solid pharmaceutical high-density polyethylene bottle for packaging.

The invention relates to an isoniazide injection and a preparation method thereof, every 1000 ml of the isoniazide injection contains 50 g of isoniazide, anhydrous disodium hydrogen phosphate and methionine, every 1000 ml of the isoniazide injection contains 3.5-4.0 g of anhydrous disodium hydrogen phosphate and 10.2-12.6 g of methionine, so that the isoniazide injection has good stability, the preparation method is simple, and the isoniazide injection is suitable for industrial production. And complicated processes such as nitrogen charging and oxygen content control are not needed.

The application discloses a high performance liquid chromatography-tandem mass spectrometry method for detecting the concentration of isoniazid in human cerebrospinal fluid, and belongs to the technical field of analytical chemistry and clinical therapeutic drug monitoring. The method comprises the following steps: short column and rapid gradient elution are adopted to realize chromatographic separation within 3.5 minutes; isoniazid and a deuterium internal standard thereof are specifically detected in a multiple reaction monitoring mode by optimizing mass spectrometry parameters; and sample pretreatment is performed by using one-step acetonitrile precipitation. Verification shows that the lower limit of quantification of the method reaches 5 ng / mL, the linear range is 5-4000 ng / mL, and the precision, accuracy and stability all meet the standards. The application has the advantages of ultrahigh sensitivity, rapid analysis, simple operation and strong anti-interference capability, and provides a precise and reliable drug concentration monitoring tool for individualized treatment of patients with tubercular meningitis.

The invention discloses a novel cyclic peptide compound. The structure of the novel cyclic peptide compound is shown as a formula (I). The compound has a remarkable inhibition effect on mycobacterium tuberculosis and mycobacterium marinum, is equivalent to a first-line drug isoniazide, and can generate a synergistic or additive effect when being combined with clinically common antibiotics. The invention also discloses application of a pharmaceutical composition containing the compound in preparation of medicines for treating and / or preventing mycobacterium infection diseases.