37 results about "Meropenem" patented technology

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 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 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.

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 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.

The invention discloses a multi-drug resistant pseudomonas aeruginosa PAS57 strain and an application of the multi-drug resistant pseudomonas aeruginosa PAS57 strain. The preservation number of the pseudomonas aeruginosa PAS57 is GDMCC No: 67235. The pseudomonas aeruginosa PAS57 can be used for preparing a bacterial strain. According to the application disclosed by the invention, a KirbyBauer (KB) drug sensitivity experiment shows that the PAS57 is resistant to the levofloxacin, the ciprofloxacin, the meropenem, the imipenem and the tobramycin. The strain disclosed by the invention can be used for screening a novel antibacterial drug which is effective to the multi-drug-resistant pseudomonas aeruginosa, and a new way is provided for development of drugs for treating diseases caused by the pseudomonas aeruginosa.

The present application relates to the technical field of medicine, in particular to the application of meropenem or aztreonam combined with nalidixic acid in the preparation of antibacterial drugs. The checkerboard dilution method minimum inhibitory concentration test, dynamic time-kill curve and galleria mellonella animal test prove that nalidixic acid can enhance the antibacterial activity of meropenem or aztreonam against carbapenem-resistant klebsiella pneumoniae, reduce the minimum inhibitory concentration of meropenem or aztreonam against carbapenem-resistant klebsiella pneumoniae, and when meropenem or aztreonam is combined with nalidixic acid, the combination shows significant synergistic antibacterial effect in vitro and in vivo against carbapenem-resistant klebsiella pneumoniae. Meropenem combined with nalidixic acid has synergistic antibacterial effect against OXA-48, NDM, KPC, IMP, VIM-producing carbapenem-resistant klebsiella pneumoniae; aztreonam combined with nalidixic acid has synergistic antibacterial effect against KPC-producing carbapenem-resistant klebsiella pneumoniae.

The invention belongs to the field of detection, and particularly discloses a method for simultaneously detecting concentrations of six drugs in blood, and the method comprises the following steps: detecting a sample to be detected by using liquid chromatography-mass spectrometry, and determining the content of the drugs in the sample to be detected according to a detection result and a standard curve, the medicine is prepared from meropenem, vancomycin, voriconazole, linezolid, tacrolimus and cyclosporine A. The invention further discloses a preparation method of the medicine. According to the invention, LC-MS / MS is adopted to simultaneously detect the blood concentration of six drugs in blood, and the method has the advantages of high separation degree, high sensitivity, high accuracy, fast detection speed and the like, provides a reliable basis for clinical precise medication, and improves the safety and effectiveness of immunosuppressor combined antibacterial drug treatment.

The application discloses soil sphingan box bacteria C3 and application thereof, the soil sphingan box bacteria (Sphingopyxis terrae) C3 is preserved in China typical culture preservation center (CCTCC) on January 30, 2026, and the preservation number is CCTCC NO: M 2026296.It can tolerate high concentration (2000 mg / L) meropenem, and can be used as the only carbon source and energy source to carry out efficient degradation, 2000 mg / L meropenem can be degraded by 50% within 72 hours, and the degradation rates of 4 mg / L and 50 mg / L meropenem can reach 100% and 70% within 12 hours respectively, and has wide application prospect in the biological removal of meropenem in related pharmaceutical wastewater, hospital wastewater and urban sewage.

The invention discloses a screening method and application of a carbapenem pneumonia resistant traditional Chinese medicine inhibitor, and belongs to the technical field of biological medicine. The carbapenem-resistant klebsiella pneumoniae inhibitor high-throughput screening system is constructed on the basis of the carbapenem enzyme activity detection fluorescent probe, and the carbapenem enzyme inhibition component in the white mulberry root bark is successfully screened as the phellinus igniarius ketone G. When the inhibitor is combined with meropenem for use, metabolism of carbapenem-resistant klebsiella pneumoniae on meropenem can be remarkably inhibited, the inhibition efficiency of meropenem on strains is greatly improved, and an efficient combined medication scheme with application value is provided for clinically resisting carbapenem-resistant klebsiella pneumoniae infection.

The present invention provides an antimicrobial combination comprising three different antimicrobial agents The first antimicrobial agent is selected from ceftazidime, polymyxin E, polymyxin B, and pharmaceutically acceptable derivatives thereof; the second antimicrobial agent is selected from zidovudine, doxycycline, fosfomycin and pharmaceutically acceptable derivatives thereof; and the third antimicrobial agent is selected from levofloxacin, doxycycline, fosfomycin, meropenem, rifampicin, gentamicin, polymyxin B / E, and pharmaceutically acceptable derivatives thereof; wherein the combination includes at least one of levofloxacin, doxycycline, rifampicin, fosfomycin, or a pharmaceutically acceptable derivative thereof; provided the combination is not (1) polymyxin E / B, zidovudine and rifampicin or (2) ceftazidime, zidovudine and fosfomycin. Also provided is an antimicrobial combination comprising three antimicrobial agents, wherein the first antimicrobial agent is ceftazidime or a pharmaceutically acceptable derivative thereof; the second antimicrobial agent is zidovudine or a pharmaceutically acceptable derivative thereof; and the third antimicrobial agent is polymyxin E or a pharmaceutically acceptable derivative thereof.

This invention provides the application of norzelamin in the preparation of NDM-1 enzyme inhibitors. Through cefotaxime hydrolysis assays, checkerboard minimum inhibitory concentration (MIC) tests, growth curves, bactericidal curves, hemolysis tests, and *Gnaphalium affine* infection experiments, it was demonstrated that norzelamin can inhibit NDM-1 enzyme activity and exhibits good synergistic antibacterial activity with the carbapenem antibiotic meropenem, enhancing the protective effect of meropenem against *Gnaphalium affine* larval infection models. Therefore, norzelamin, as a potential adjuvant for β-lactam antibiotics, can enhance the antibacterial effect of β-lactam antibiotics by inhibiting NDM-1 enzyme activity, which is of great significance for the clinical development of safe and effective β-lactam antibiotic adjuvants.

This invention belongs to the field of pharmaceutical analytical chemistry technology, and provides a method for detecting meropenem concentration in human serum based on UPLC-MS / MS. This method uses acetonitrile protein precipitation for serum sample pretreatment, with C... 18 Separation was performed using a reversed-phase column with gradient elution of water-methanol as the mobile phase, and the total run time was 3 min. Mass spectrometry was performed in positive ion electrospray ionization mode and multiple reaction monitoring mode. Method validation results showed that meropenem was effective in the range of 1.563–100 μg / mL. ‑1 The linear relationship was good within the range, and the lower limit of quantitation was 1.563 μg·mL. ‑1 The intra-day and inter-day precision RSD were <5.69%, and the accuracy RE was within ±14.20%. Matrix effect, recovery, and stability all met the requirements for biological sample analysis. This method was used to determine the concentration of meropenem in human serum, providing technical support for therapeutic drug monitoring (TDM).

This invention belongs to the field of pharmaceutical intermediate synthesis technology, specifically relating to a method for synthesizing meropenem side chains. Using meropenem side chain intermediates and dimethylamine aqueous solution as raw materials, ethanol as solvent, and tributylphosphine as catalyst, the reaction is carried out. After the reaction, the solution is adjusted to acid, filtered, and crude meropenem side chain is obtained. The crude meropenem side chain is then added to water, alkali is adjusted, solvent extraction is performed, acid is adjusted again, crystallization occurs, filtration is performed, and drying is carried out to obtain purified meropenem side chains. This invention has low preparation cost, is easy to operate, and is suitable for industrialization. It can completely remove impurities such as meropenem side chain disulfides, obtaining high-purity purified meropenem side chains with a purity of over 99.9%, which is beneficial for improving the purity of subsequent synthesized meropenem.