64 results about "Meropenem" patented technology

The invention discloses a preparation method and application of a sepsis-related encephalopathy model based on HLA II type gene humanized mice. According to the invention, HLA DP401 / DRA-IA beta- / -transgenic humanized mice are utilized, and the HLAII type gene humanized mouse sepsis model is prepared through mouse cecum seroperitoneal infection (CS) and meropenem intervention. The sepsis encephalopathy model can be comprehensively evaluated through indexes such as clinical score MSS, serum and hippocampal tissue inflammatory cytokine detection, hippocampal tissue microglial cell activation, hippocampal neuron spinous process change, transcriptomics, behavioral change and the like, and the sepsis encephalopathy model can be used for screening therapeutic drugs and therapeutic schedules; the HLA II type gene humanized mouse sepsis-related encephalopathy model provided by the invention can be used for infectious encephalopathy pathogenesis research, new drug research and development and safety evaluation.

The invention belongs to the technical field of biological medicine, and particularly discloses application of tea polyphenol combined with meropenem to preparation of a medicine for resisting carbapenem drug-resistant bacteria, and the carbapenem drug-resistant bacteria are animal source blaNDM-5 positive escherichia coli and / or klebsiella pneumoniae. A trace bouillon chessboard method, a cefoxitin hydrolysis test, a time-sterilization curve, a greater wax moth infection model and the like prove that the tea polyphenol and carbapenem antibiotic meropenem generate a good synergistic antibacterial effect, and the tea polyphenol can also inhibit the activity of NDM-5 enzyme; meanwhile, the treatment and protection effects of meropenem on a greater wax moth infection model are improved. It is found for the first time that tea polyphenol can reverse the drug resistance of carbapenem drug-resistant bacteria to meropenem and enhance the antibacterial activity of meropenem to carbapenem drug-resistant bacteria, the synergistic effect is remarkable, use is easy, popularization is easy, and good application value is achieved.

The invention relates to the technical field of pharmaceutical analysis, and provides a method for identifying the structure of an impurity in a meropenem bulk drug, which is used for identifying the structure of the impurity in the meropenem bulk drug by liquid chromatography-mass spectrometry. In the chromatographic conditions of the liquid chromatography-mass spectrometry, a mobile phase comprises a mobile phase A and a mobile phase B, and the mobile phase A is a formic acid aqueous solution with the mass fraction of 0.1%-0.3%; and the mobile phase B is an acetonitrile solution containing formic acid with the mass fraction of 0.1-0.3%. By means of the technical scheme, the problems that in the related technology, the variety of structure identification of impurities of meropenem raw material medicine is few, and the accuracy and the like are not high when an existing detection method is used for identification are solved.

The invention discloses an antibody as well as a preparation method and application thereof. The antibody has good binding activity with OXA-23 type carbapenem enzyme, and can reduce the carbapenem drug resistance level of the acinetobacter baumannii, so that the clinical use concentration of meropenem is reduced, and the treatment effect of meropenem on the acinetobacter baumannii is improved. In addition, the antibody disclosed by the invention can also inhibit OXA-23 protein secreted by bacteria, prevent the bacteria from hydrolyzing carbapenem antibiotics, increase the concentration of antibiotics in a medication part, and facilitate the removal of mixed infection with acinetobacter baumannii. The invention provides a new strategy for treating acinetobacter baumannii infection, and the application prospect is wide.

The present disclosure provides medicaments and health essentials for the treatment or prevention of bacterial infections. More specifically, the present disclosure is a drug for treating or preventing bacterial infections, which is a drug comprising Compound A or a pharmaceutically acceptable salt thereof and meropenem or a pharmaceutically acceptable salt thereof, characterized in that the drug is administered intravenously to a subject. Alternatively, the present disclosure provides a drug for the treatment or prevention of bacterial infections, which is a drug comprising Compound A or a pharmaceutically acceptable salt thereof and meropenem or a pharmaceutically acceptable salt thereof, characterized in that: the compound A or the pharmaceutically acceptable salt thereof is preferably selected from the group consisting of compound A, meropenem and meropenem; wherein Compound A or a pharmaceutically acceptable salt thereof is administered to a subject in such a manner that the activity of meropenem or a pharmaceutically acceptable salt thereof is increased compared to when not used in combination.

The invention provides a compound for preparing an MBL and / or SBL enzyme inhibitor, application of the compound and a medicine of the compound, and belongs to the field of medicine. The structure of the compound is shown as a formula I. The compound provided by the invention has good and broad-spectrum inhibitory activity on clinically common metal beta lactamase (MBL) and serine beta lactamase (SBL), can be used as an MBL and / or SBL enzyme inhibitor, and is used for preparing antibacterial drugs, especially drugs for resisting drug-resistant bacteria. In addition, the compound disclosed by the invention is combined with beta-lactam antibiotic meropenem and the like for use, so that the compound has relatively good antibacterial activity on various beta-lactam antibiotic drug-resistant bacteria. The compound disclosed by the invention has great potential in preparation of MBL and SBL dual broad-spectrum inhibitors and medicines for resisting beta-lactam antibiotic-resistant bacteria. The invention provides a new choice for the use of antibacterial drugs, and has a good application prospect.

The present invention belongs to the field of pharmaceutical technology and relates to a class of compounds with antibacterial uses, specifically N-allyl-substituted indoline-2-one-3-hydrazine dithiocarboxylate derivatives. The compounds are shown as formula (I): wherein, R1 represents a C1-C4 alkyl group, and R4, R5, R6 and R7 represent a halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group or a trifluoromethoxy group. The compounds involved in the present invention have the activity of inhibiting New Delhi metallo-β-lactamase 1 (NDM-1). When combined with β-lactam antibiotics such as meropenem, they can restore the sensitivity of superbugs to the corresponding antibiotics and can be used as antibacterial drugs.

The application discloses a flagellum inhibiting peptide of pseudomonas aeruginosa and a preparation method and application thereof, and the sequence of the flagellum inhibiting peptide is Lys-Ile-Gly-Leu-Phe-Arg-Trp-Arg. The synthetic inhibiting peptide has a time-dependent self-assembly ability, can gradually evolve from scattered granular into filamentous structure, and finally forms a stable net-like morphology. The synthetic inhibiting peptide can significantly inhibit the flagellum motility of PAO1 and other strains of pseudomonas aeruginosa, and has synergistic antibacterial activity when combined with allicin, ciprofloxacin, meropenem, levofloxacin, polymyxin B and the like. Moreover, the synthetic inhibiting peptide has obvious bacteriostatic and healing-promoting effects on burn wound infection.

This invention relates to an oxobenzohexacyclic borate ester compound, its preparation method, and its uses, belonging to the pharmaceutical field. The derivatives of this invention are compounds represented by Formula I, or their salts, conformational isomers, or optical isomers. The oxobenzohexacyclic borate ester derivatives provided by this invention exhibit good, broad-spectrum inhibitory activity against clinically common metallo-β-lactamases (MBL) and serine β-lactamases (SBL), and show good antibacterial activity against various drug-resistant bacteria when used in combination with the β-lactam antibiotic meropenem. Therefore, the series of derivatives provided by this invention have great potential in the preparation of dual broad-spectrum inhibitors of MBL and SBL and in drugs to overcome β-lactam antibiotic-resistant bacteria. Formula I.

The invention discloses a dual-regulation pharmaceutical composition for sepsis treatment, a preparation method and application, and belongs to the technical field of biological medicine, and the pharmaceutical composition comprises doxorubicin liposome, all-trans retinoic acid phospholipid complex nanoparticles and antibiotics. Preferably, the doxorubicin liposome is prepared from the sialic acid modified doxorubicin liposome, the sialic acid modified all-trans retinoic acid phospholipid compound nanoparticles and meropenem. Dynamic monitoring of myeloid-derived suppressor cells MDSCs and sialic acid binding immunoglobulin type lectin-E (SiglecE) positively expressed myeloid-derived suppressor cells, namely SiglecE + MDSCs cell subsets, in the middle and later periods of sepsis is used as an evaluation index of the immunosuppression state, and dual regulation and control of sepsis acute inflammation and immunosuppression are achieved. The method has remarkable advantages in the aspects of increasing the survival rate, precisely targeting immunosuppression, improving the drug delivery efficiency and the like, and a brand new solution is provided for clinical treatment of sepsis.

The invention provides a method for detecting N-nitrosomeropenem as an impurity in meropenem, and belongs to the field of pharmaceutical analytical chemistry. According to the detection method, an LC-MS method is adopted, and the chromatographic conditions are as follows: a Waters Atlants HILIC Silica liquid chromatographic column (150mm * 4.6 mm, 5 [mu] m) is adopted as a chromatographic column; a mobile phase A is ammonia water with the volume concentration of 0.04%-0.06%, and a mobile phase B is formic acid acetonitrile with the volume concentration of 0.05%-0.2%; and gradient elution. According to the method, the N-nitrosomeropenem impurity and meropenem can be effectively separated, the meropenem impurity N-nitrosomeropenem can be effectively detected, and the method is high in specificity and applicability, high in detection sensitivity, good in linear relation and high in precision and accuracy.

The invention discloses a preparation method of meropenem dimer impurities, which comprises the following steps: (1) adding meropenem into methanol, then adding acetic acid into the methanol, and stirring at 40-80 DEG C for 3-6 hours; (2) continuously adding meropenem and a water removal agent into the reaction liquid in the step (1), and stirring at-10 to 10 DEG C for 10 to 12 hours; and (3) filtering, cooling the filtrate to-20 to-15 DEG C, dropwise adding tetrahydrofuran into the filtrate for crystallization, and filtering to obtain the meropenem dimer impurity. The method is simple to operate, the raw material conversion rate can reach 99% or above, the product purity is 95% or above, and the method can be directly used as a reference substance for qualitative and quantitative research on meropenem dimerization impurities, so that the product quality is more effectively controlled.

The invention discloses application of primurin as an antibiotic synergist, and belongs to the field of new medical application of primurin. Through an NDM-5 enzyme inhibition test, a trace chessboard dilution method, a time-sterilization curve test and other tests, it is found that primurin can significantly inhibit the activity of an NDM-5 enzyme and recover the antibacterial activity of meropenem to NDM-5-producing escherichia coli. Therefore, it is determined that primurin can be used as an inhibitor of beta-lactamase; when the beta-lactamase is combined with the beta-lactam antibiotics, the hydrolysis of the beta-lactamase on the beta-lactam antibiotics can be reduced or even eliminated, the beta-lactam antibiotics are effectively protected, and the sensitivity of beta-lactamase-producing drug-resistant bacteria on the beta-lactam antibiotics is recovered; the invention has application prospects in preparation of antibiotic synergists or preparation of drugs or preparations for inhibiting pathogenic bacteria producing beta-lactamase by combined use with antibiotics, and the like.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to novel antibacterial application of a beta-lactamase inhibitor, combined antibacterial application of the beta-lactamase inhibitor and meropenem, and a technical scheme of application of a pharmaceutical composition of the beta-lactamase inhibitor and meropenem to treatment of bacterial infection.

The invention provides an sgRNA molecule of a targeted IMP-4 gene and a biomacromolecular compound containing the sgRNA molecule, the biomacromolecular compound forms a CRISPR-Cas3 system for targeted removal of the IMP-4 drug-resistant gene, and the invention also provides a method for targeted removal of the IMP-4 drug-resistant gene in a strain by using the system. According to the CRISPR-Cas3 system provided by the invention, the directed gene clearance rate of the strain carrying the IMP-4 drug-resistant gene can reach 100%. The minimum inhibitory concentration of the Escherichia coli subjected to targeted removal of IMP-4 to meropenem is averagely reduced by 71.11 times compared with that of a strain without targeted removal of IMP-4.

The invention discloses application of L-histidine in preparation of an NDM enzyme inhibitor, a medicine for treating bacterial infectious diseases or an antibiotic synergist. The invention discloses that L-histidine can inhibit the hydrolytic activity of NDM enzyme for the first time, has a relatively strong effect of resisting drug-resistant pathogenic bacteria in vivo and in vitro when being combined with the antibiotic meropenem for use, and can effectively improve the curative effect of meropenem; when the L-histidine and meropenem combined medicine is used for treating gram-negative bacteria infectious diseases, the survival rate of mice can be remarkably increased and the inflammation level of organisms can be reduced by the combined medicine of the L-histidine and meropenem. The invention provides a new thought for the control of pathogenic bacteria of drug-resistant bacteria, and also provides a new strategy for the prevention and treatment of increasingly serious gram-negative bacterial infection.

The application belongs to the field of pharmaceutical chemistry and medicine, and relates to a cephalosporin compound and its use in preparing antibacterial drugs. Specifically disclosed are the use of a cephalosporin compound, or a pharmaceutically acceptable salt thereof, or a medicine composition taking the cephalosporin compound as an effective active ingredient in preparing a medicine for preventing and treating gram-negative drug-resistant bacterial infections. The compound can irreversibly covalently bind to metal beta-lactamase, inhibit the hydrolysis of beta-lactam antibiotics, effectively reduce the minimum inhibitory concentration (MIC) value and the blood bacterial load of gram-negative drug-resistant bacteria in a mouse with abdominal infection, and can be combined with beta-lactam antibiotics such as meropenem to prepare a compound preparation for treating diseases such as infections caused by gram-negative drug-resistant bacteria.

This invention discloses the application of cinnamaldehyde as a potentiator for β-lactam antibiotics in inhibiting carbapenem-resistant Escherichia coli (CREC). The study confirms that cinnamaldehyde not only inhibits the growth of drug-resistant E. coli but also enhances the antibacterial activity of β-lactam antibiotics, effectively reducing the minimum inhibitory concentration (MIC) of meropenem and cefqinome against drug-resistant E. coli. Further research shows that high concentrations of cinnamaldehyde inhibit New Delhi metallo-β-lactamase-5 (NDM-5) enzyme. This discovery provides a new strategy for addressing the resistance of CREC to β-lactam antibiotics.

The invention relates to the technical field of drug concentration detection. The invention provides a method for detecting meropenem and open-loop metabolite thereof in serum and cerebrospinal fluid, which comprises the following steps: adding an internal standard solution into a to-be-detected sample solution containing meropenem and open-loop metabolite thereof, mixing, pretreating to obtain supernate, taking the supernate, and performing LC-MS / MS detection to obtain the meropenem and open-loop metabolite thereof. And then calculating by adopting a peak area normalization method to obtain the concentrations of the meropenem and the open-loop metabolite of the meropenem. The result detected by the method disclosed by the invention is stable and reliable, the accuracy is high, the specificity is strong, the applicability is good, and a sensitive, simple and reliable method is provided for monitoring the drug concentration of meropenem and the open-loop metabolite of meropenem; clinical drug monitoring is facilitated, clinical reasonable drug use is guided, and adverse reactions are reduced.

The invention relates to the technical field of medicines, in particular to application of combination of meropenem or aztreonam and paromomycin sulfate in preparation of antibacterial drugs. The experimental result of the in vitro combination effect shows that when meropenem or aztreonam is combined with paromomycin sulfate, the meropenem or aztreonam has a remarkable synergistic effect on carbapenem-resistant klebsiella pneumoniae, and paromomycin sulfate can reduce the bacteriostatic concentration of meropenem or aztreonam, so that the meropenem or aztreonam can be used for preparing the medicine for treating the carbapenem-resistant klebsiella pneumoniae. Therefore, the paromomycin sulfate can be used for improving the inhibition effect of meropenem or aztreonam on carbapenem-resistant klebsiella pneumoniae.

The invention discloses application of daphnetin as an NDM-1 and NDM-5 double-target inhibitor in antibacterial synergism, and belongs to the technical field of medicines. In order to solve the problem that a method for effectively inhibiting metallo-beta-lactamase is lacked in the prior art, through NDM-1 and NDM-5 enzyme inhibition tests, a trace chessboard dilution method, a time-sterilization curve and other tests, it is found that daphnetin can significantly inhibit the activity of NDM-1 and NDM-5 enzymes and restore the antibacterial activity of meropenem to escherichia coli producing NDM-1 and NDM-5. Therefore, the daphnetin provided by the invention can be used as an NDM-1 and NDM-5 double-target inhibitor, is applied to antibiosis, synergism and treatment of bacterial infectious diseases, and has wide medical application.

The invention relates to application of a bacterial metabolite in preparation of a metallo-beta-lactamase inhibitor and a drug for improving the sensitivity of bacteria to antibiotics and a pharmaceutical composition, and belongs to the technical field of biological medicines. The bacterial metabolite is N-acetyl-L-methionine and / or methyl malonic acid. The NDM-5 protein is expressed, separated and purified through a genetic engineering means, and an enzyme activity inhibition test, an enzyme inhibition ratio and semi-inhibition concentration determination prove that bacterial metabolites, namely N-acetyl-L-methionine and methylmalonic acid, can inhibit the activity of NDM-5 enzyme in a dose-dependent manner. The invention also proves that the N-acetyl-L-methionine and the methylmalonic acid can recover the antibacterial activity of the meropenem to NDM-1, NDM-5 and NDM-9 positive drug-resistant bacteria and have wide application prospects in the aspect of treating drug-resistant bacteria infectious diseases through a checkerboard method for measuring the minimum inhibitory concentration, a time-sterilization curve method and the like.

Methods of treating or ameliorating urinary tract infection (UTI), including complicated urinary tract infection (cUTI) and acute pyelonephritis (AP), comprising administering a composition comprising a cyclic boronic acid ester vaborbactam in combination with meropenem are disclosed herewith.

The present application relates to a kind of for anti-infection prodrug and its application. Specifically, the present application provides a meropenem prodrug, the structure of the meropenem prodrug is as shown below. The meropenem prodrug of the present application has excellent therapeutic effect on bacterial biofilm-related infection.

The application discloses a kind of pharmaceutical composition, and the pharmaceutical active ingredient of its drug includes desoximycin and meropenem.The composition can synergistically and efficiently inhibit klebsiella pneumoniae, especially KPC-2 positive carbapenem-resistant klebsiella pneumoniae and NDM-5 positive carbapenem-resistant klebsiella pneumoniae, with application prospect.

The application discloses a 7-sulfur-substituted chromone-3-formaldehyde compound shown in a formula I or a derivative thereof shown in a formula II and a preparation method and application thereof, wherein R is selected from a methylthio group, a thiazole-2-yl group, a pyrimidine-2-yl group, a pyridine-2-yl group, an imidazole-2-yl group, a (1-methyl-pyridine-4) group-4-thiazole-2-yl group, a benzothiazole-2-yl group, a quinoline-2-yl group, a benzothiophene-2-yl group, a (4-carboxylpropyl)-5-thiophene-2-yl group, and n represents the number of S; when R is selected from a thiophene-2-yl group, n is selected from 0, 1 or 2; when R is selected from groups other than the thiophene-2-yl group, n is selected from 0. The compound and the derivative thereof have a better inhibiting effect on NDM-1, can enhance the antibacterial effect in combination with imipenem and meropenem, and in addition, the synthesis route is simple and easy to operate.

The invention relates to a culture medium and a method for producing penicillin G sodium degrading enzyme. The culture medium is composed of the following components: 20 g / L of galactose, 8 g / L of yeast extract powder, 10 g / L of ammonium sulfate, 0.5 g / L of MgSO4. 7H2O, 0.5 g / L of NaCl, 0.5 g / L of KH2PO4, 1.5 g / L of K2HPO4, and 0.05% of Tween-80. According to the invention, 0.75 mmol / L of meropenem is creatively added to induce degrading enzyme when the strain is cultured for 9 hours. The method comprises the step of adjusting fermentation conditions such as seed culture time, pH value of a culture medium, inoculum size, culture temperature, rotating speed, liquid loading amount and the like so as to improve the yield of the penicillin G sodium degrading enzyme. The fermentation culture medium and the culture method provided by the invention have a proliferation promoting effect on the penicillin G sodium degrading enzyme, and have important significance on industrial production of the penicillin G sodium degrading enzyme by sphingobacterium sp. And harmless treatment of antibiotics in the environment.

The application discloses small-granularity meropenem crystals and a preparation method thereof. Through a further reaction-dissolution coupling crystallization process after dissolving a raw material crude product by adding a lye, uniform small-granularity meropenem crystal products can be obtained. The obtained crystal products are white block or flaky shuttle-shaped crystal habits, have high content (≥99.5%), low total residual solvent (≤0.2%), and high process yield (≥90%); the aqueous solution is colorless, clear and transparent, and has an acidity of 4.84-5.12; the granularity is uniform, the fluidity is good (the angle of repose is ≤35°), the granularity distribution is small (D50 is ≤25 μm, and D90 is ≤70 μm), and the product redissolution time is fast (≤75 s); after the obtained products are placed under the condition of 30 ± 2 ℃ and 60 ± 5% RH for three months, no obvious changes are found in various indexes, and the products have good stability. The required equipment is simple, the processing scale is large, the operation is simple, industrial production can be carried out, and the method has good technical economy and high industrial application value.

The invention discloses a palladium-carbon catalyst for meropenem and a preparation method thereof, and the preparation method comprises the following steps: step 1, preparing a carrier: adding activated carbon into an aluminum ammonium sulfate solution, and stirring uniformly at a set temperature; adjusting the pH value of the system to 9-9.5 by using ammonium bicarbonate, and continuously reacting for preset time; after the reaction is finished, filtering, drying an obtained filter cake, and calcining at high temperature in a nitrogen atmosphere to obtain a catalyst carrier; 2, mixing a palladium oxalate solution with a cesium sulfate solution, adding the catalyst carrier prepared in the step 1, and concentrating until the system is anhydrous; and introducing hydrogen under a high-temperature condition for reduction to obtain the palladium-carbon catalyst. The palladium-carbon catalyst can maintain the specific surface area of the activated carbon and increase the density of the activated carbon, is easier to precipitate compared with pure activated carbon, and improves the filtering speed; the prepared palladium-carbon does not contain chloride ions, the activity of the palladium-carbon is improved, and meanwhile, cesium oxide is introduced into the palladium-carbon, so that the selectivity of the catalyst is improved.

The present invention discloses the use of anisaldehyde / meropenem or their combination in the preparation of a medicament for preventing and / or treating Erwinia infection; the present invention discovers for the first time that anisaldehyde has an inhibitory effect on the formation of Erwinia biofilm; meropenem has an inhibitory effect on the growth of Erwinia; the combination of anisaldehyde and meropenem can effectively inhibit the formation of Erwinia biofilm; and anisaldehyde can enhance the drug sensitivity of meropenem to Erwinia, indicating a good application prospect in agricultural medicaments for preventing and / or treating Erwinia infection.