82 results about "Carbapenem" patented technology

The invention discloses an antibacterial peptide based on D-type amino acid and application of the antibacterial peptide, and the antibacterial peptide is characterized in that the amino acid sequence is w-r-r-w-r-r-w-w-r-k-r (dTrp-dArg-dArg-dTrp-dArg-dArg-dTrp-dTrp-dArg-dLys-dArg). The antibacterial peptide can be synthesized through an Fmoc solid-phase chemical method, the synthesis difficulty is low, and the in-vivo antibacterial activity is good. The antibacterial peptide especially has broad-spectrum killing activity on carbapenem-resistant pseudomonas aeruginosa, pseudomonas aeruginosa, klebsiella pneumoniae, escherichia coli, methicillin-resistant staphylococcus aureus and staphylococcus aureus, is low in hemolytic toxicity, can reach half or more of cell survival rate under medium and low concentration, almost has no toxic effect on cells, and can be used for preparing the antibacterial peptide with a broad-spectrum killing activity on carbapenem-resistant pseudomonas aeruginosa, klebsiella pneumoniae, escherichia coli, methicillin-resistant staphylococcus aureus and staphylococcus aureus. The stability is good, the operability is high, and the cost is low.

The invention discloses a carbapenem drug resistance gene detection reagent or kit, the detection reagent comprises a PCR detection liquid, the PCR detection liquid comprises upstream and downstream primer sequences and probe sequences of target genes, and the target genes are KPC, OXA-23, NDM, VIM and IMP. The invention also discloses application of the reagent or the kit. The reagent / kit provided by the invention has simple components, only comprises a PCR detection liquid and negative and positive quality control, can obtain detection results of five major carbapenem drug resistance genes, namely KPC, OXA-23, NDM, VIM and IMP, within about 50 minutes only once, and is simple and convenient to operate, low in detection cost, short in detection time and high in sensitivity. In addition, the lowest detectable concentration of detection of carbapenem drug resistance genes KPC, OXA-23, NDM, VIM and IMP is 10 copy / mL, and the sensitivity is high.

The invention discloses an application of an antibacterial peptide and an application of the antibacterial peptide in preparation of antibacterial drugs for treating carbapenem-resistant pseudomonas aeruginosa, klebsiella pneumoniae (ATCC700603), escherichia coli (ATCC25922), staphylococcus aureus and methicillin-resistant staphylococcus aureus, the antibacterial peptide is characterized in that the sequence is w-r-r-w-k-r-w-w-r-r, and the sequence is shown in the description. All amino acids are D-type amino acids; the antibacterial peptide can be used as an antibacterial substance in wash supplies, food preservative additives, medical consumable antibacterial agents and cosmetics, can be synthesized through an Fmoc solid-phase chemical method, and is low in synthesis difficulty and good in in-vivo antibacterial activity. Particularly, the antibacterial peptide has broad-spectrum killing activity against carbapenem pseudomonas aeruginosa, klebsiella pneumoniae (ATCC700603), escherichia coli (ATCC25922), staphylococcus aureus and methicillin-resistant staphylococcus aureus, the cell survival rate of the antibacterial peptide within the range of medium and low concentration (2 mu g / mL-32 mu g / mL) reaches half or more, the toxicity is small, the toxicity is almost avoided, the operability is high, and the antibacterial peptide can be widely applied to the field of medical application. The cost is low.

The invention designs a carbapenem drug-resistant gene nucleic acid fluorescent PCR method detection kit and application thereof, the kit uses Taqman fluorescent probe multiple amplification technology to detect carbapenem drug-resistant genes, the kit comprises a nucleic acid reaction liquid Mix1 and a nucleic acid reaction liquid Mix2, the nucleic acid reaction liquid Mix1 is used for detecting drug-resistant genes IMP, NDM and OXA48, the nucleic acid reaction liquid Mix2 is used for detecting drug-resistant genes IMP, NDM and OXA48, and the nucleic acid reaction liquid Mix2 is used for detecting drug-resistant genes IMP, NDM and OXA48. The nucleic acid reaction liquid Mix2 is used for detecting drug resistance genes VIM, KPC and OXA23. The method is high in detection specificity, and the detection result is visual and easy to interpret. Clinical doctors are assisted to judge respiratory tract pathogen infection more comprehensively and more accurately. The kit covers six carbapenem drug resistance genes, is more comprehensive and accurate in detection, and is high in specificity and sensitivity. Meanwhile, multiple sample types can be detected, a sputum sample, an excrement sample and a rectum swab sample are detected through paramagnetic particle extraction, and pure bacterial colonies are directly detected without extraction.

The invention relates to an antibacterial peptide and application thereof. The amino acid sequence of the antibacterial peptide is as shown in SEQ ID No. 1. The antibacterial peptide has excellent broad-spectrum antibacterial activity, for example, the antibacterial peptide has antibacterial activity on bacteria of the genus Staphylococcus (Staphylococcus), the genus Acinetobacter (Acinetobacter) and the genus Bacillus (Bacillus). Under the background that the global bacterial drug resistance problem is increasingly severe and traditional antibiotics gradually lose efficacy on multi-drug-resistant bacteria, a new treatment means is provided for treating bacteria such as methicillin-resistant staphylococcus aureus, carbapenem-resistant acinetobacter baumannii and bacillus subtilis which bring huge threats to public health. And a new possibility is provided for solving the problem that no medicine can be used clinically.

The present invention relates to the pharmaceutical field, and provides a boric acid β-lactamase inhibitor or a use thereof. The boric acid β-lactamase inhibitor is a compound shown in formula (I), or an optical isomer or a pharmaceutically acceptable salt thereof: formula (I). The ultra-broad-spectrum boric acid β-lactamase inhibitor of the present invention has an inhibition effect on A, B, C, and D enzymes, and carbapenem drug-resistant bacteria such as Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Acinetobacter baumannii, and Pseudomonas aeruginosa.

The present application relates to the field of biotechnology, in particular to a carbapenem-resistant escherichia coli phage and application thereof.A new escherichia coli phage vB_EOP_Se009 is isolated and purified, and the phage has good sterilization effect on carbapenem-resistant escherichia coli.The phage has strong tolerance to temperature and pH, is high in specificity and stability, can effectively solve the problem that carbapenem-resistant escherichia coli is resistant to multiple antibiotics, and provides an experimental basis for developing a preparation for preventing or treating carbapenem-resistant escherichia coli infection in clinic, and has great clinical application potential.

The present application belongs to the technical field of artificial intelligence assisted drug screening, and particularly relates to a method for screening active molecules against carbapenem-resistant enterobacteriaceae based on a LightGBM algorithm, a medium and an apparatus. The method constructs a LightGBM integrated learning framework, fuses ADME rules optimized for the outer membrane barrier characteristics of gram-negative bacteria and multi-target molecule docking verification, effectively solves the problem of data imbalance caused by the scarcity of active samples and the huge compound library, and significantly improves the hit rate of screening. The present application also provides a computer readable storage medium and an electronic device. By storing and executing the above program, the present application can quickly and standardizedly identify anti-CRE candidate molecules from a large number of compounds, greatly reducing the computing power cost and time cycle of new drug research and development. The present application is designed to overcome the bottleneck of gram-negative bacterial outer membrane permeation, and provides an efficient, accurate and intelligent screening tool for combating CRE super-bacterial infections.

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.

This invention relates to compounds of formula (I) and methods of treatment using the compounds. The compounds of the invention can be used in combination with antibacterial agents to treat bacterial infections. More specifically, the compounds of formula (I) can be used in combination with a class of antibacterial agents known as carbapenems. The novel compounds of the present invention are enzyme inhibitors and more particularly are metallo-β-lactamase inhibitors.

This invention relates to the synthesis of compounds that can be used to treat bacterial infections in combination with other antibacterial agents, and more specifically in combination with a class of antibacterial agents known as carbapenems. The compounds resulting from the novel methods of the present invention are enzyme inhibitors and more particularly are metallo-β-lactamase inhibitors.

The present application relates to a kind of targeting bacterial UDP-N-acetylglucosamine enolpyruvate transaminase antibacterial compound and its application, the antibacterial compound is S-(4-chlorobenzyl) chloro isothiourea, its chemical structure is as shown in formula I: I;Or its pharmaceutically acceptable salt, stereoisomer, solvate, crystal form, isotopically labeled or prodrug.The antibacterial compound of the present application can effectively inhibit the growth of klebsiella pneumoniae, including carbapenem-resistant klebsiella pneumoniae and high virulence klebsiella pneumoniae;It also has good bacteriostatic effect on escherichia coli and pseudomonas aeruginosa;It is expected to be applied to the clinical treatment of infection caused by drug-resistant klebsiella pneumoniae and high virulence klebsiella pneumoniae and other pathogenic bacteria, and has important clinical significance and social benefits.

The application provides a drug delivery system for targeted treatment of inflammatory diseases and a preparation method and application thereof, and belongs to the technical field of biological drugs. The drug delivery system for targeted treatment of inflammatory diseases is M2 type macrophages phagocytizing drug-loaded nanoparticles, wherein the drug-loaded nanoparticles comprise a biodegradable high molecular material for coating drugs. The drug delivery system prepared by the application realizes lung targeted delivery through the natural inflammatory chemotaxis characteristics of M2 type macrophages, and in combination with the drug slow-release effect of the drug-loaded nanoparticles, the drug targeting and availability are significantly improved, so that the drug efficacy is improved, the biological safety is good, and a new effective means is provided for the clinical treatment of various inflammatory diseases including carbapenem-resistant Klebsiella pneumoniae (CRKP) pneumonia.

The invention belongs to the technical field of gene detection, and particularly relates to a carbapenem drug resistance gene detection device and method.The carbapenem drug resistance gene detection device comprises a detector, a detection cavity is formed in the detector, a detection unit is arranged in the detection cavity, and the detection unit comprises a pneumatic control module, an optical detection module and a constant temperature module; a sealing cover for sealing the detection cavity is arranged on the top surface of the detector; a micro-fluidic chip is placed on a suction cup, the micro-fluidic chip is pressed to be adsorbed on the suction cup, then a sealing cover is closed, an electric telescopic rod moves downwards, a first spring pushes a connecting plate, the connecting plate drives the suction cup to move downwards, and the suction cup drives the chip to move downwards; when the micro-fluidic chip is placed in the groove, the bottom surface of the chip is in contact with the inner wall of the groove, and then the electric telescopic rod is closed, so that the micro-fluidic chip is fixed in the groove, and the micro-fluidic chips of different models and sizes can be fixed through the suction cup.

Compositions and methods are provided for treating bacterial infections, including those that are challenging to treat by conventional medications, such as hospital acquired bacterial pneumonia (HABP), ventilator associated bacterial pneumonia (VABP), and bacteremia, caused by carbapenem-resistant bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa.

The invention discloses a carbapenem drug resistance marker screening method and system based on a cross-species compressed Debrueine diagram and a medium. The method comprises the following steps: starting from whole genome sequencing data of gram-negative bacteria belonging to different species and carbapenem drug phenotypes of the gram-negative bacteria, constructing a compressed Debrueine graph based on cross-species joint data, and taking existence / deletion of nodes in the graph as unified genetic variation characteristics. Performing correlation analysis on the nodes and the drug resistance phenotypes by using a linear hybrid model to obtain a candidate node set related to the phenotypes; k-mer is extracted based on the candidate node sequence, and secondary statistical screening is completed in combination with chi-square test and mutual information; and finally determining a group of carbapenem drug-resistant genetic markers which can be applicable across species through a hierarchical feature selection strategy of random forest and XGBoost. Efficient dimension reduction of large-scale cross-species genome data, cross-species consistent variation representation and high-interpretability marker screening are achieved.

This invention discloses a primer and probe set, kit, and method for detecting carbapenem resistance genes using point-of-care testing (POCT), belonging to the field of gene detection technology. The carbapenem resistance genes include: NDM, KPC, VIM, IMP, OXA, and GES; the primers and probes for the NDM gene include: SEQ ID NO.1, SEQ ID NO.2, and SEQ ID NO.3; the primers and probes for the KPC gene include: SEQ ID NO.4, SEQ ID NO.5, and SEQ ID NO.6; the primers and probes for the VIM gene include: SEQ ID NO.7, SEQ ID NO.8, and SEQ ID NO.9; the primers and probes for the IMP gene include: SEQ ID NO.10, SEQ ID NO.11, and SEQ ID NO.12; the primers and probes for the OXA gene include: SEQ ID NO.13, SEQ ID NO.14, SEQ ID NO.15, SEQ ID NO.16, SEQ ID NO.17, SEQ ID NO.18, SEQ ID NO.19, SEQ ID NO.20, and SEQ ID NO.21; and the primers and probes for the GES gene include: SEQ ID NO.22, SEQ ID NO.23, and SEQ ID NO.24. The primer and probe set, kit, and method of this invention can be used to detect carbapenem resistance genes NDM (75 subtypes), KPC (232 subtypes), VIM (90 subtypes), IMP (101 subtypes), GES (64 subtypes), and OXA-48, 23, 51, and 213 groups in a single detection tube. They have the advantages of short detection time, simple operation, wide coverage, good specificity, and prevention of contamination.

The invention relates to the technical field of biological detection, in particular to a primer probe composition for detecting a KPC type carbapenem drug-resistant gene and application of the primer probe composition. In order to solve the technical problems of long detection time, missing detection of partial subtypes, existence of cross reaction, insufficient sensitivity and the like in KPC gene detection in the prior art, the invention discloses a primer probe composition for detecting KPC type carbapenem drug resistance genes, the primer probe composition comprises a primer pair, the primer pair comprises a forward primer and a reverse primer, and the forward primer and the reverse primer are used for detecting the KPC type carbapenem drug resistance genes. The nucleotide sequence of a forward primer is shown as SEQ ID NO: 1, and the nucleotide sequence of a reverse primer is shown as SEQ ID NO: 2; the nucleotide sequence of the probe is as shown in SEQ ID NO: 3. Meanwhile, a reaction system is optimized, a matched detection kit and a standardized detection process are constructed, detection can be completed within 45 minutes, and cross reaction with carbapenemase genes such as NDM, VIM, IMP and OXA does not exist.

This invention relates to the field of high-throughput targeted sequencing technology, and particularly to a primer set and its applications for detecting important drug resistance and virulence genes in multidrug-resistant pathogens. Specifically, it includes primers for detecting various drug-resistant bacteria, such as third-generation cephalosporin-resistant Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Acinetobacter baumannii, and rifampicin-resistant Mycobacterium tuberculosis. This invention offers advantages such as speed, efficiency, strong targeting, and high specificity. It is suitable for analyzing the prevalence and differential distribution of multiple important drug resistance and virulence genes carried in metagenomic samples from various environments or pathogenic materials, and can be used to assess the risk of related environments, further guiding preventative and clinical treatment medications.

The invention discloses an aromatic polyketone compound as well as a preparation method and application thereof. The compound GaB (3) has an effect of treating infection of multiple drug-resistant bacteria. The compound is obtained by being separated from a secondary metabolite of the symbiotic Streptomyces sp.QHH-9511 of licheniformis, and the compound 2, the compound 3, the compound 4 and the compound 5 are new compounds. According to the present invention, the research results show that the GaB can effectively sterilize a variety of drug-resistant bacteria (methicillin-resistant staphylococcus aureus, vancomycin-resistant enterococcus, carbapenem-resistant acinetobacter baumannii, multi-drug-resistant pseudomonas aeruginosa, multi-drug-resistant salmonella, and the like); in addition, the compound has the characteristics of broad-spectrum sterilization, biofilm formation inhibition and low-frequency drug resistance, and can be combined with other antibiotics to cope with super bacteria. Mechanism research shows that GaB is combined with glucosamine-6-phosphate synthetase (GlmS) to prevent synthesis of cell walls so as to play an antibacterial role, and a plurality of constructed living body models show that the compound can effectively reduce the content of bacteria in a body and promote wound repair and has in-vivo medication safety. The research result shows that the GaB can be used as a safe and effective novel pilot natural active small molecule for resisting infection of multiple drug-resistant bacteria.

The application discloses a D-type amino acid-based antibacterial peptide and application thereof, and has the amino acid sequence of w-r-r-w-r-r-w-w-r-k-r (dTrp-dArg-dArg-dTrp-dArg-dArg-dTrp-dTrp-dArg-dLys-dArg). The antibacterial peptide can be synthesized by Fmoc solid-phase chemical synthesis, has low synthesis difficulty, and has good in-vivo antibacterial activity. The antibacterial peptide has broad-spectrum killing activity on carbapenem-resistant pseudomonas aeruginosa, pseudomonas aeruginosa, klebsiella pneumoniae, escherichia coli, methicillin-resistant staphylococcus aureus and staphylococcus aureus, has low hemolytic toxicity, can reach more than half of the cell survival rate at a medium or low concentration, has almost no toxic effect on cells, has good stability, has strong operability, and is low in cost.

The invention relates to a paper elution and drug sensitive test combined method, and belongs to the field of biological medicine. The invention provides a paper elution and drug sensitive test combined method, which comprises the following steps of: preparing drug sensitive systems with different drug combinations and concentration ranges by combining drug sensitive paper elution and broth dilution methods; according to the method, a single drug sensitive system and a combined drug sensitive system are established, the minimum inhibitory concentration MIC during single drug use and combined use is measured, and the interaction between drugs is quantitatively evaluated by calculating a partial inhibitory concentration index. According to the test method, the tablets can be prepared on site according to the required experimental dosage, waste is reduced, operation is easy and convenient, the tablets are easy to store, the detection result has good consistency with that in the prior art, the test method can be widely applied to drug sensitivity detection of carbapenem drug-resistant gram-negative bacteria, and the test method has the advantages of being economical, convenient and rapid to operate, accurate in result and the like and has good application prospects. The method has a wide application prospect in a multi-drug combined treatment scheme for screening multi-drug-resistant bacteria.

The invention discloses an antibacterial 10 peptide, which is characterized in that the sequence of the antibacterial 10 peptide is w-k-r-w-r-r-r-w-w-r-r (dTrp-dLys-dArg-dTrp-dArg-dArg-dTrp-dTrp-dArg-dArg), and all amino acids are D-type amino acids. The antibacterial peptide provided by the invention has good antibacterial activity on various pathogenic bacteria, can be synthesized through an Fmoc solid-phase chemical method, and is low in synthesis difficulty and relatively good in-vivo antibacterial activity. The antibacterial peptide has broad-spectrum killing activity on multidrug-resistant acinetobacter baumannii, carbapenem-resistant pseudomonas aeruginosa and standard strains of acinetobacter baumannii, pseudomonas aeruginosa, klebsiella pneumoniae, escherichia coli, enterobacter cloacae, methicillin-resistant staphylococcus aureus and staphylococcus aureus, and is low in hemolytic toxicity and high in killing activity. Under medium and low concentration (2 microgram / mL to 32 microgram / mL), the cell survival rate can reach more than half, and the cell culture medium has no toxic effect on cells, and is good in stability, strong in operability and low in cost.

The invention discloses a carbapenem drug resistance gene detection primer group based on multiple PCR-time-of-flight mass spectrometry, a detection kit and a kit using method, and through a large number of screening and verification experiments, a multiple primer group suitable for time-of-flight mass spectrometry detection is obtained. Therefore, the multi-PCR-time-of-flight mass spectrometry detection of the multi-drug-resistant genes of carbapenem-resistant enterobacteriaceae bacteria becomes possible. The detection kit prepared by adopting the primer group can be used for simultaneously detecting and identifying 10 common carbapenem drug-resistant genes, including klebsiella pneumoniae KPC gene, NDM gene, IMP gene, VIM gene and OXA gene, acinetobacter baumannii OXA gene, NDM gene, Escherichia coli OXA gene, IMP gene and serratia marcescens VIM gene. Meanwhile, the kit is high in sensitivity and specificity, dozens of times of detection can be carried out in the same batch, so that the detection efficiency is greatly improved, and the kit is suitable for rapid screening and genetic typing of carbapenem drug-resistant bacteria in clinical samples.

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.

This invention relates to an antimicrobial peptide and its applications. The amino acid sequence of the antimicrobial peptide is at least one of the sequences shown in SEQ ID No. 1 to SEQ ID No. 8. The antimicrobial peptide exhibits excellent broad-spectrum antimicrobial activity, for example, against Acinetobacter spp. (…). Acinetobacter ), Pseudomonas aeruginosa ( Pseudomonas aeruginosa ) and Bacillus spp. ( Bacillus This bacterium possesses antibacterial activity. Against the backdrop of increasingly severe global bacterial resistance and the gradual ineffectiveness of traditional antibiotics against multidrug-resistant bacteria, this provides a new treatment option for carbapenem-resistant bacteria such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Bacillus subtilis, which pose a significant threat to public health, and offers new possibilities for solving the clinical dilemma of "no available drugs."

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.

This invention belongs to the field of detection technology for carbapenem-resistant Enterobacteriaceae, and provides an anti-KPC-2 carbapenemase nanobody Nb-KPC-2 and its applications. The anti-KPC-2 carbapenemase nanobody Nb-KPC-2 has the amino acid sequence shown in SEQ ID NO.1. This invention lays the foundation for constructing a low-cost and stable immunoassay method for KPC-2 carbapenemases. Utilizing the characteristics of small size, good stability, and ease of labeling, nanobodies can be applied to the rapid detection of pathogenic microorganisms, such as the preparation of diagnostic test strips, reagents, and kits; they can also be applied to basic research and tool development, such as as molecular probes, isolation and purification kits, and the construction of core components for targeted therapy molecules; enabling early and accurate screening and identification of drug-resistant Gram-negative bacteria producing KPC-2 carbapenemases, guiding precise clinical medication and infection control.

The invention relates to an anti-OXA-48 carbapenemase monoclonal antibody as well as a preparation method and application thereof. According to the invention, OXA-48 type carbapenemase recombinant protein is taken as an immunogen, BALB / c mice are immunized to prepare the anti-OXA-48 type carbapenemase monoclonal antibody, and gene sequences of a heavy chain variable region and a light chain variable region of the antibody are provided. The monoclonal antibody disclosed by the invention is strong in specificity and high in sensitivity, can be subjected to specific reaction with OXA-48 type carbapenemase, does not react with carbapenemase such as NDM-1, IMP-1, KPC-2, VIM-2 and OXA-23, can be applied to various immunological detection methods, provides a new tool for prevention and detection of OXA-48 type carbapenemase, and has a wide application prospect. The OXA-48 carbapenemase can also be used for developing drugs for preventing and treating diseases caused by OXA-48 carbapenemase infection, and has good application value.