60 results about "Polymyxin" patented technology

The present application relates to the technical field of biology, and particularly relates to a mesenchymal stem cell culture medium and a preparation method and application thereof.The mesenchymal stem cell culture medium comprises a basic culture medium, fetal bovine serum, basic fibroblast growth factor, polymyxin B and deionized water.The present application can simultaneously improve the proliferation activity of mesenchymal stem cells and the secretion performance of HGF by simultaneously adding the basic fibroblast growth factor and the polymyxin B in the basic culture medium; more stem cells can be in the active proliferation and division process by limiting the content of the basic fibroblast growth factor in the mesenchymal stem cell culture medium to 5-50 ng / mL; and the secretion performance of HGF can be improved while the cell proliferation activity is maintained by limiting the content of the polymyxin B in the mesenchymal stem cell culture medium to 50-100 mu g / mL.

The invention relates to the technical field of biological medicine, in particular to application of flufenamic acid in preparation of a polymyxin E antibacterial synergist. The invention discloses an application of flufenamic acid in preparation of a polymyxin E antibacterial synergist, the flufenamic acid has no obvious antibacterial effect on salmonella when being independently used, but the flufenamic acid and polymyxin E can enhance the antibacterial activity of the polymyxin E on the salmonella and reduce the use dosage of the polymyxin E when being jointly used in and out of an animal body, so that the antibacterial effect of the polymyxin E on the salmonella can be enhanced. The antibacterial activity of the polymyxin E on salmonella is enhanced, and the drug resistance of the polymyxin E is inhibited. Flurfenamic acid is approved to be used for other purposes as FDA, and when the flurfenamic acid is combined with polymyxin E, the flurfenamic acid has the characteristic of high safety, and meanwhile, the generation of the drug resistance of the polymyxin E drugs can be effectively avoided. The invention provides a basis for mining a new antibacterial prevention and control strategy for the polymyxin E drug-resistant bacteria.

This invention provides a compound drug for treating melioidosis, its preparation method, and its application. The drug comprises active components of traditional Chinese medicine, a bioactive preparation, and a pharmaceutically acceptable carrier. The active components of traditional Chinese medicine are primarily extracts of Scutellaria baicalensis, Coptis chinensis, Fagopyrum dibotrys, and Polygonum cuspidatum. The bioactive preparation includes polymyxin B, homoserine lactonease, and recombinant human β-defensin 3. The components work synergistically to construct a comprehensive intervention system covering all pathological stages, including biofilm disruption, sterilization, anti-endotoxin activity, intracellular bacterial clearance, immune regulation, and tissue repair. This system can effectively disrupt bacterial biofilms, kill multidrug-resistant strains, neutralize endotoxins, and eliminate latent intracellular bacteria, addressing the core pain points of existing melioidosis treatments, such as strong drug resistance, significant toxic side effects, and high recurrence rates. The preparation process of this invention is carried out under low-temperature and sterile conditions throughout, which fully preserves the stability of the active ingredients, making it suitable for industrial production. The drug can be prepared in various dosage forms, covering all clinical subtypes of melioidosis, and possesses clinical application value and promising prospects for widespread application.

The invention provides Kineococcus G2 and application of the Kineococcus G2 in preparation of a pigment with antioxidant activity, the Kineococcus new strain G2 is CCTCC No. M20242602, the strain is spherical, the size is 1.0 * 1.5 mu m, the optimal growth temperature is 30-37 DEG C, the pH value is 7.0-9.0, and the salt concentration is 1.0%-2.0%. The strain G2 is not sensitive to bacitracin, ciprofloxacin and norfloxacin, and is sensitive to novobiocin, polymyxin, gentamicin, piperacillin, ofloxacin, erythromycin, streptomycin, kanamycin, rifampicin, ampicillin, vancomycin, carbenicillin, chloramphenicol, tetracycline, penicillin, cefoperazone, oxacillin, amoxicillin and neomycin. Pigment generated by fermentation of the G2 strain has good antioxidant activity, and when the concentration is 10 micrograms / mL, the scavenging activity on DPPH is 25.00%, the scavenging activity on hydroxyl radicals is 80.58%, and the iron ion reducing capacity is 1.57, which are all higher than those of contrast beta-carotenoid. The application of the new Kineococcus strain G2 can lay a foundation for the research of antioxidant drugs such as medical treatment and health care product development.

A novel 10 peptide capable of inhibiting the growth of bacteria that are resistant to existing polymyxin, a pharmaceutical composition comprising the novel 10 peptide, and an application thereof in the treatment or prevention of bacterial infections.

The application provides a polymyxin B-loaded nano preparation and a preparation method and application thereof, and belongs to the field of biological nanotechnology.The method comprises the following steps: (1) preparing a water-in-oil emulsion: mixing a water solution of polymyxin B and a dichloromethane solution of polylactic acid-glycolic acid copolymer to obtain a water-in-oil emulsion; (2) preparing an ethanol aqueous solution of hyaluronic acid; (3) mixing the water-in-oil emulsion and the ethanol aqueous solution of hyaluronic acid, and stirring to obtain a nano dispersion; (4) vacuum rotary evaporation of the nano dispersion, collection of a colloidal dispersion, and dispersion of the colloidal dispersion in water to obtain a nano particle solution.The nano preparation prepared by the application does not need a chemical crosslinking agent, and thus effectively avoids problems caused by the introduction of chemical crosslinking.The preparation process is simple and easy to control, has good safety, has good biocompatibility, and provides a basis for the approval of clinical trials and industrial development of atomization drug delivery of antibiotics.

This application discloses a fluorescent probe for labeling the outer membrane of Gram-negative bacteria, its preparation method, and its application. The fluorescent probe uses polymyxin (with its hydrophobic tail and two amino acid residue pairs removed) as a targeting group specifically targeting the outer membrane of Gram-negative bacteria. This structure can specifically bind to the lipopolysaccharide structure in the outer membrane, and is then linked to the fluorophore rhodamine, which has switching properties, to design and synthesize a fluorescent dye. This fluorescent probe, possessing fluorescent switching properties, can be applied to super-resolution imaging of the outer membrane of Gram-negative bacteria.

The application belongs to the field of genetic engineering and medical engineering, and discloses virK Application of gene in regulation of Klebsiella pneumoniae virulence. The application finds that the expression level of the gene is significantly increased in polymyxin-resistant mutant strains through transcriptome analysis, virK Further research shows that the expression of the gene is regulated by the PhoP / PhoQ two-component regulatory system. The application constructs virK Gene deletion mutant strains and complementary strains, and compares the virulence difference of the strains in an animal infection model, finds that virK The virulence of the deletion strain is significantly reduced, and the complementary strain can restore the virulence phenotype, indicating that virK The gene plays an important role in the regulation of Klebsiella pneumoniae virulence. The application first finds that PhoP can regulate virK Gene expression, and affects the virulence phenotype of Klebsiella pneumoniae through the regulation pathway, thereby revealing a new virulence regulation mechanism, and providing a theoretical basis for subsequent targeted intervention.

The invention provides an endotoxin adsorbent and a preparation method thereof. The preparation method comprises the following steps: S1, preparing epoxidized styrene-divinyl benzene resin; s2, dispersing the epoxidized styrene-divinyl benzene resin obtained in the step S1 into an organic solvent, wherein the epoxidized styrene-divinyl benzene resin with carboxyl obtained by reaction still contains an epoxy group; s3, mixing and reacting the epoxidized styrene-divinyl benzene resin with carboxyl obtained in the step S2 with a reaction solution containing an amination reagent to obtain styrene-divinyl benzene resin with both amido and carboxyl; s4, the styrene-divinyl benzene resin with the amido and carboxyl obtained in the step S3 reacts with polymyxin B under the action of a condensing agent, and the endotoxin adsorbent is obtained. The endotoxin adsorbent prepared by the method is excellent in adsorption performance, strong in specificity, high in mechanical strength, good in biocompatibility and not easy to fall off.

This invention relates to the field of microbial technology and discloses a biocontrol strain for controlling peanut stem rot, wherein the biocontrol strain is *Bacillus pilaris* (…). Paenibacillus peoriae This invention also provides a biocontrol agent containing this strain and its preparation method. Genomic analysis revealed that this strain contains gene clusters encoding active substances such as fusarium and polymyxin, exhibiting significant antagonistic activity against peanut stem rot fungus, and broad-spectrum inhibitory activity against various plant pathogenic fungi, including wheat stem base rot fungus and rapeseed sclerotinia. Furthermore, this strain possesses the ability to secrete auxin, produce proteases, and produce cellulases. The prepared inoculum, applied through root irrigation, can construct a preventative biological barrier in the rhizosphere, providing both disease prevention and growth promotion effects. This invention provides a highly efficient germplasm resource for the green control of crop diseases.

The application provides a recombinant polymyxin enzyme and a preparation and application method thereof, an amino acid sequence of the recombinant polymyxin enzyme is shown as SEQ ID NO. 1, and the recombinant polymyxin enzyme is obtained through site-directed mutation on an amino acid sequence of a wild-type polymyxin enzyme derived from Brevibacillus laterosporus. The recombinant polymyxin enzyme can specifically recognize and cut a peptide bond between a tripeptide side chain and a cyclic heptapeptide ring in a polymyxin structure and a peptide bond between threonine and diaminobutyric acid inside the cyclic heptapeptide ring, and further can specifically degrade or neutralize the recombinant polymyxin enzyme of polymyxin.

The present application belongs to the technical field of antibacterial medicine, and particularly relates to a benzene sulfonyl indole structure modified ruthenium polypyridyl complex with the function of inhibiting bacterial toxin as well as a preparation method and application thereof. The benzene sulfonyl indole structure modified ruthenium polypyridyl complex has the following structure: The benzene sulfonyl indole structure modified ruthenium polypyridyl complex not only has excellent antibacterial ability, but also does not induce bacterial drug resistance. The benzene sulfonyl indole structure modified ruthenium polypyridyl complex can be used in combination with polymyxin B to achieve better antibacterial effect. In addition, it is found that the benzene sulfonyl indole structure modified ruthenium polypyridyl complex has certain antibiofilm effect, and the mechanism thereof is further studied. The complex can also effectively inhibit the hemolysis phenomenon caused by bacteria and has concentration dependence.

The application belongs to the technical field of biological medicine, and discloses application of Ebselen as a synergist of polymyxin in inhibition of salmonella. It is found that Ebselen combined with polymyxin has good synergistic effect on salmonella in vitro and in vivo experiments. In a mouse salmonella infection model, the bacterial load in the liver of animals treated with EBS combined with polymyxin is significantly lower than that treated with single drug. The survival rate of animals treated with EBS combined with polymyxin is significantly higher than that treated with EBS and polymyxin alone. Compared with traditional antibiotics and antibiotic combination to kill salmonella, the synergistic bactericidal effect of Ebselen and polymyxin is less likely to induce bacterial drug resistance, and Ebselen has the characteristics of wide source, multiple effects and good treatment effect, which has good research and application significance for exploring antibiotic synergistic replacement and solving bacterial drug resistance.

The invention discloses an artificial synthesis method and application of malonyl coenzyme A. An artificial synthesis route for synthesizing malonyl-CoA by taking beta-alanine (beta-ala) as a precursor is constructed by heterologous expression of aminotransferase and malonyl-CoA reductase: firstly, under the catalysis of transaminase, amino of beta-ala is transferred to alpha-keto acid (such as pyruvic acid, oxaloacetic acid or alpha-ketoglutaric acid and the like), and then the malonyl-CoA is obtained; an intermediate product 3-oxopropionic acid and corresponding amino acid are formed; and the malonyl-CoA is generated from the 3-oxopropionic acid under the action of the malonyl-CoA reductase. According to the method, the defects existing in a natural malonyl-CoA synthesis route, such as low carbon utilization rate, energy substance ATP consumption, greenhouse gas CO2 release, pyruvate dehydrogenase (PDH) of route enzymes and acetyl-CoA carboxylase (ACC) which are strictly regulated and controlled, are overcome, and high yield of products taking malonyl-CoA as a precursor, including light flavomycin, octanoic acid, phloroglucinol, pentadecheptaene, natamycin, spinosad and the like, is realized.

This invention discloses a single-chain antibody 3G4 that targets and binds to mobile polymyxin resistance proteins and its applications. The amino acid sequence of single-chain antibody 3G4 is shown in SEQ ID NO.2. The mobile polymyxin resistance proteins are MCR-1 and / or MCR-2 proteins. Single-chain antibody 3G4 can specifically bind to the functional catalytic region of the mobile polymyxin resistance proteins, thereby inhibiting their function. Single-chain antibody 3G4, its encoding gene, and an expression vector containing the encoding gene can be used to prepare detection reagents for mobile polymyxin resistance proteins or recombinant bacteria with inhibited polymyxin resistance. The recombinant bacteria are Gram-negative bacteria capable of expressing single-chain antibody 3G4. The single-chain antibody 3G4 provided by this invention can efficiently target polymyxin resistance proteins, blocking their modification of lipid A on the outer membrane of Gram-negative Enterobacteriaceae, thereby reversing bacterial resistance to polymyxins.

The invention belongs to the technical field of biological medicines, and discloses a cyclized antibacterial peptide CycP-1 targeting multiple drug-resistant klebsiella pneumoniae, and a composition and application thereof. The amino acid sequence of the antibacterial peptide is shown as SEQ ID NO.1, cysteine residues at the first site and the 24th site in a molecule of the antibacterial peptide form a disulfide bond, and the antibacterial peptide is in cyclization conformation and shows good in-vitro protease stability. Experiments show that the antibacterial peptide has a remarkable inhibiting effect on multi-drug-resistant and pan-drug-resistant klebsiella pneumoniae, and when the antibacterial peptide is combined with antibiotics, the antibacterial effect can be enhanced, drug resistance can be reversed or reduced, and generation of drug resistance can be delayed. A mouse pneumonia model in-vivo experiment further proves that after oral administration of the antibacterial peptide, the lung tissue bacterial load of a pan-drug resistant klebsiella pneumonia infected mouse can be remarkably reduced, lung pathological injury is relieved, the survival rate of the infected mouse is remarkably increased, and the effect is better when the antibacterial peptide is combined with polymyxin B.

The invention relates to the field of microbiological inspection and food safety monitoring, and particularly discloses a chromogenic culture medium for detecting staphylococcus aureus, a preparation method of the chromogenic culture medium and a test piece. The chromogenic culture medium comprises a basic nutrient component, a compound bacteriostatic agent, a compound chromogenic enzyme substrate, metal salt, cold water gel, an activating agent and a confirmation reaction substrate, and the compound bacteriostatic agent comprises lithium chloride, polymyxin B sulfate, nalidixic acid and 2-dimethyl-3-hydroxy-4-pyridone; the compound chromogenic enzyme substrate is prepared from 5-bromo-6-chloro-3-indolyl phosphate disodium salt and 5-bromo-4-chloro-3-indole-beta-D-glucoside sodium salt, and the compound chromogenic enzyme substrate is prepared from a compound chromogenic enzyme substrate and a compound chromogenic enzyme substrate, wherein the compound chromogenic enzyme substrate is prepared from sodium 5-bromo-6-chloro-3-indolyl phosphate disodium salt; the metal salt comprises zinc sulfate, anhydrous magnesium sulfate and manganese chloride; the cold water gel comprises carboxymethyl cellulose and guar gum; the activating agent is calcium chloride. The prepared test piece has the advantages of being high in selectivity, easy and convenient to operate, rapid in detection and visual and accurate in result.

The invention discloses an antibacterial peptide, a pharmaceutical composition and application, and belongs to the field of polypeptide medicines.The antibacterial peptide forms a novel annular conformation by introducing n-leucine and 2-aminobutyric acid to construct a parent nucleus structure. The affinity of the antibacterial peptide to the main component phosphatidylglycerol of a bacterial cell membrane is remarkably improved, is improved by 31 times or more compared with polymyxin B and is improved by 16 times or more compared with D50 peptide, and the selectivity of the antibacterial peptide to the main component phosphatidylcholine of a mammalian cell membrane is improved by hundreds of times or more compared with that of a control peptide. The polymyxin B peptide has extremely low toxicity to HK-2 kidney cells, and the biological safety of the polymyxin B peptide is obviously superior to that of polymyxin B and D50 peptide. The minimum inhibitory concentration of the antibacterial peptide to gram-negative bacteria is as low as 0.03 mu g / mL, is about 33 times higher than that of polymyxin B, and is 17-33 times higher than that of D50 peptide. The treatment effect of the antibacterial peptide is obviously superior to that of polymyxin B and D50 peptide in various infection models, and the antibacterial peptide is expected to be developed into a novel anti-infection drug and is used for preventing and treating various infections.

This invention belongs to the field of medical and pharmaceutical technology, and specifically relates to an antibacterial composition and its application. It comprises osimertinib mesylate and polymyxin. This invention is the first to demonstrate the novel pharmaceutical use of osimertinib mesylate as a synergistic antibacterial adjuvant for polymyxin. Experimental results show that osimertinib mesylate can significantly enhance the antibacterial activity of polymyxin against multidrug-resistant Gram-negative bacteria, effectively reduce the minimum inhibitory concentration of polymyxin, thereby reducing the clinical dosage of polymyxin and lowering the risk of its inherent nephrotoxicity and neurotoxicity. Furthermore, this invention reveals that the combined use of osimertinib mesylate and polymyxin can delay or reverse bacterial resistance to polymyxin, improve the survival rate of infected animal models, and broaden the antibacterial spectrum.

The present invention relates to a pharmaceutical product in the form of a storage stable lyophilisate or a pharmaceutical formulation in the form of a sterile solution for parenteral administration. Both the lyophilisate and solution consist essentially of a polymyxin selected from polymyxin E, polymyxin B, or a pharmaceutically acceptable derivative thereof, and zidovudine or a pharmaceutically acceptable derivative thereof. The solution further includes an aqueous carrier.

The present application relates to a kind of bacteriophage lytic enzyme LysSPYS2, containing bacteriophage lytic enzyme composition and its application, bacteriophage lytic enzyme LysSPYS2 sequence is as shown in SEQ ID No.1, the bacteriophage lytic enzyme has high-efficiency, broad-spectrum bactericidal effect;It has lytic effect to a variety of bacteria, can be used as bacteriostatic agent;Further, the bacteriophage lytic enzyme is combined with polymyxin B, can exert synergistic antibacterial effect, significantly reduce the amount of antibiotic;The bacteriophage lytic enzyme can also be used with Magnolol, realize outstanding bacteriostatic effect.

This invention relates to a phage lysin LysSPYS1, a composition containing the phage lysin, and their applications. The sequence of the phage lysin LysSPYS1 is shown in SEQ ID No. 1. This phage lysin exhibits highly efficient and broad-spectrum bactericidal activity; it has a lytic effect on a variety of bacteria and can be used as a bacteriostatic agent. Furthermore, combining this phage lysin with polymyxin B can exert a synergistic antibacterial effect, significantly reducing the amount of antibiotics used. The phage lysin can also be used in combination with magnolol to achieve a prominent antibacterial effect.

The invention belongs to the technical field of biological medicine, and discloses an anti-MCR-1 nano antibody, the amino acid sequence of which is as shown in SEQ ID NO.1 or SEQ ID NO.9 or SEQ ID NO.17 or SEQ ID NO.25. The invention also discloses a preparation method of the anti-MCR-1 nano antibody. According to the nano antibody disclosed by the invention, the MIC value of the polymyxin to MCR-1 positive polymyxin drug-resistant bacteria can be reduced from 16 mu g / mL to 8 mu g / mL, the bactericidal effect of the polymyxin to MCR-1 positive polymyxin drug-resistant escherichia coli is enhanced, and a new treatment strategy is provided for clinical treatment of bacterial infectious diseases.

Disclosed herein are conjugate agents comprising a targeting moiety (in certain embodiments, a polymyxin or related compound) conjugated directly or indirectly to a payload moiety, compositions comprising the conjugate agents, and methods of making and using the conjugate agents.

The application provides a polymyxin secretion engineering strain and a construction method and application thereof, and belongs to the technical field of biotechnology. One of the purposes of the application is to provide a polymyxin synthesis engineering strain, and the second purpose is to provide a polymyxin secretion model. In the application, a polymyxin synthesis gene cluster is expressed by using an exogenous inducible promoter in P. polymyxa, and a chassis cell is constructed; the chassis cell is used as a starting strain, and an efflux transporter gene pmxC and pmxD are knocked out, so that a polymyxin efflux down-regulation type chassis cell is constructed; a recombinant vector containing the gene pmxD is back-supplemented in the polymyxin efflux down-regulation type chassis cell, and the expression of pmxD is started by using a pathogenic bacterium-biased endogenous promoter. In this way, an engineering strain for intensively secreting polymyxin by exogenous induction of pathogenic bacteria can be obtained.

The application discloses synthesis of a novel Schiff base gold (III) compound and antibacterial application thereof, and belongs to the technical field of medicine preparation; gold sodium aurothiomalate has significant antibacterial activity, but the Au-S bond thereof is easily broken by intracellular reducing thiol, and the gold sodium aurothiomalate is metabolized before reaching a target point to produce toxic side effects; based on the gold sodium aurothiomalate, developing a gold compound with stronger stability is one of strategies for overcoming drug-resistant bacteria; the Schiff base itself has antibacterial activity, and after being combined with gold (III) ions, the Schiff base can stabilize gold atoms and improve the activity of the gold atoms; in vitro antibacterial activity shows that Au6 and Au13 have significant antibacterial advantages on carbapenem and polymyxin-resistant Klebsiella pneumoniae, the minimum inhibitory concentration (MIC) is 10 micromoles, and the antibacterial activity is at least 16 times higher than that of the gold sodium aurothiomalate; in vivo antibacterial activity experiments prove that Au6 and Au13 can reduce mouse skin infection and promote wound healing, and can prolong the survival time of abdominal infection mice, and have important practical application value.

The application discloses application of mulberroside D in synergistic polymyxin antibacterial activity, and belongs to the technical field of medicines, and particularly relates to application of mulberroside D in synergistic polymyxin antibacterial activity. The application discloses application of mulberroside D in preparation of a product for enhancing antibacterial activity and / or bactericidal activity of an antibacterial drug. The mulberroside D can effectively synergize in-vivo and in-vitro antibacterial activity of polymyxin on multi-drug resistant bacteria, can produce synergistic antibacterial effect, and provides a new treatment strategy for clinical treatment of bacterial infectious diseases.

The application discloses a compound polymyxin inhalation preparation, which is composed of a polymyxin polypeptide, an aminoglycoside antibiotic and a pharmaceutically acceptable auxiliary material. The molar ratio of the polymyxin polypeptide to the aminoglycoside antibiotic in the inhalation preparation is 1:20-1:80. Compared with single preparation or a compound preparation with a molar ratio of less than 1:20, the compound preparation with the molar ratio can significantly reduce lung toxicity and achieve a significant effect of clearing multiple drug-resistant bacteria in lung infection. The compound drug is delivered by using an inhalation liquid preparation dosage form, so that the total drug delivery efficiency of atomization inhalation is greatly improved, the median particle size of the drug is smaller, and the proportion of particles with a size of less than 5 microns is more than 55%, so that the drug is more easily inhaled into the lung to achieve an anti-infection treatment effect.

The application discloses a chromogenic differential culture medium for separating duck Riemerella anatipestifer and application thereof, and belongs to the field of microorganism detection. The application provides the chromogenic differential culture medium based on physiological and biochemical characteristics of the duck Riemerella anatipestifer, and the chromogenic differential culture medium takes polymyxin B and vancomycin as specific antibiotics and takes X-Glu as a chromogenic substrate. The experimental results show that the chromogenic differential culture medium can efficiently inhibit growth of miscellaneous bacteria, and the duck Riemerella anatipestifer colony presents a characteristic color, so that the dual functions of selective culture and rapid identification are realized; the duck Riemerella anatipestifer identification method developed based on the chromogenic differential culture medium has the advantages of good selectivity, intuitive identification, simple operation, accurate results and the like, and the application provides new materials and methods for identification of the duck Riemerella anatipestifer and diagnosis of duck Riemerella anatipestifer disease.