54 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 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 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 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 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 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 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.

This invention relates to a screening method and application of traditional Chinese medicine inhibitors against carbapenem-resistant Klebsiella pneumoniae, belonging to the field of biomedical technology. Based on a high-throughput screening system for carbapenem-resistant Klebsiella pneumoniae inhibitors constructed using a fluorescent probe for carbapenemase activity detection, the invention successfully screened out mulberry bark as a carbapenemase inhibitor, sanghorn ketone G. When used in combination with meropenem, this inhibitor significantly inhibits the metabolism of meropenem by carbapenem-resistant Klebsiella pneumoniae, greatly enhancing the inhibitory efficiency of meropenem against the strain, providing a highly effective and valuable combination therapy for clinical treatment of carbapenem-resistant Klebsiella pneumoniae infection.

The application discloses an antibody, a preparation method and application thereof. The antibody has good binding activity with OXA-23 type carbapenamase, can reduce the carbapenam antibiotic resistance level of acinetobacter baumannii, thereby reducing the use concentration of meropenem in clinic, and improving the treatment effect of meropenem on acinetobacter baumannii. In addition, the antibody can also inhibit the OXA-23 protein secreted by bacteria, prevent the hydrolysis of carbapenam antibiotics by bacteria, increase the antibiotic concentration at a drug application site, and is favorable for clearing mixed infections with acinetobacter baumannii. The application provides a new strategy for treating acinetobacter baumannii infections, and has a wide application prospect.

The invention discloses application of chelerythrine in preparation of drugs or antibiotic synergists for treating bacterial infectious diseases, bacteria are carbapenem antibiotic resistant bacteria, and antibiotics are carbapenem antibiotics. The invention discloses that chelerythrine can restore the sensitivity of carbapenem drug-resistant bacteria for the first time, can reduce the minimum inhibitory concentration of meropenem to bacteria for producing metal beta-lactamase by 16 times, and provides a new strategy for solving the drug resistance of bacteria.

The invention relates to quinoline-2-carboxylic acid derivatives as well as a preparation method and application thereof. The quinoline-2-carboxylic acid derivative is a compound as shown in a formula IV or pharmaceutically acceptable salt, crystal form, solvate and optical isomer thereof. In the formula, R5 is selected from aryl, substituted aryl, 5-11-membered heteroaryl and substituted 5-12-membered heteroaryl; and R6 is selected from aryl, substituted aryl, 5-12-membered heteroaryl, substituted 5-12-membered heteroaryl, C3-C8 cycloalkyl, 3-8-membered heterocycloalkyl, C1-C6 alkyl, and C1-C6 monosubstituted or polysubstituted alkyl. The compound provided by the invention is combined with cephalosporin and carbapenem antibacterial drugs, such as ceftriaxone, meropenem and the like, so that the activity of the compound for expressing drug-resistant bacteria on NDM-1 can be effectively recovered. The compound disclosed by the invention shows good NDM-1 enzyme inhibition activity and can be used as a novel NDM-1 inhibitor.

The application discloses a N-(3-cyclobutyrolactone)-4-bromobenzamide and meropenem composition and application of the composition in treatment of chronic infection of drug-resistant bacteria. After the N-(3-cyclobutyrolactone)-4-bromobenzamide and the meropenem are combined, not only can the sensitivity of a biofilm bacterium to the meropenem be significantly increased, the killing effect of the meropenem on the biofilm bacterium be improved, but also the formation amount of a Pseudomonas aeruginosa biofilm can be greatly reduced; the composition can be applied to preventing and treating chronic infection of drug-resistant Pseudomonas aeruginosa.

Methods of treating bacterial infection in immunocompromised subjects and subjects with one or more underlying malignancies include administering a combination of meropenem and vaborbactam to the subject. Suitable subjects to be treated can include a subject with a history of ongoing leukemia or lymphoma, a subject that has had an organ transplant, stem cell transplant, bone marrow transplant, or splenectomy, a subject receiving immunosuppressive medications, a subject receiving bone marrow ablative chemotherapy, a subject with neutropenia and subject suffering from or having suffered from a malignancy.

This invention discloses a purification method for crude meropenem acid. The method involves adding a solvent to a reaction vessel, cooling the mixture to 16-20°C, adding the crude meropenem acid and an antioxidant, controlling the temperature at 16-23°C, and starting to add an alkaline solution dropwise. The solution is dissolved for 30-40 minutes, with the pH of the dissolved solution controlled at 6-10. A decolorizing agent is added, and the mixture is stirred and filtered. An extractant is added for a first extraction, followed by a second extraction with the same extractant in the aqueous phase. Both aqueous phases are collected, and the temperature is controlled at 16-20°C. Dilute hydrochloric acid is added dropwise to the aqueous phase. If the mixture becomes turbid, seed crystals are added to promote crystal growth. Dilute hydrochloric acid is continued to be added until the pH reaches 1.6-2. The temperature is lowered to 0-5°C to promote crystal growth. The mixture is centrifuged, and the filter cake is washed with purified water until the filtrate is neutral. The filtrate is then rinsed with ethanol at -20 to -10°C, and finally vacuum dried at 40-50°C to obtain purified meropenem acid. This purification method significantly reduces the content of single impurities, total impurities, and polymers in the product, improving product quality and making it suitable for large-scale industrial production.