32 results about "Polymyxin B" patented technology

The invention belongs to the technical field of gene engineering, and particularly relates to a mutant of polymyxin efflux transporter and application of the mutant. The mutant is a PmxD transporter mutant, the amino acid sequence of the PmxD transporter mutant is shown as SEQ ID NO: 1, and compared with wild type PmxD, the polymyxin transport capacity of the PmxD transporter mutant (T38W) is improved by 450.46%; and the total discharge amount of polymyxin is increased by 85.72%. Meanwhile, the mutant can significantly improve the growth ability of the strain on a plate containing 250 [mu] g / mL of polymyxin B, namely significantly improve the autoresistance of paenibacillus polymyxa to polymyxin.

The invention discloses a preparation method of engineered bacteria for releasing CO gas under initiation of ultrasonic waves to kill tumor cells, and relates to a preparation method of CO carrier engineered bacteria. The invention aims to solve the problems that the existing CO carrier material is low in delivery efficiency, the CO is difficult to release efficiently and controllably in space and time at the same time, and the existing metal CO carrier material is high in toxicity. Meanwhile, the problems that the penetrating power of light waves to biological tissues is limited, and the CO release efficiency is limited due to a tumor hypoxic microenvironment are solved. The preparation method comprises the following steps: 1, modifying the surface of escherichia coli with 3-hydroxyflavone-D-alanine; and 2, continuously modifying the surface of the escherichia coli with CaO2 (at) polymyxin B. The method is used for preparing the engineered bacteria for releasing the CO gas through ultrasonic initiation to kill the tumor cells.

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 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 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 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.

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.

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 invention relates to a multifunctional bacterial cellulose gel film and a preparation method and application thereof.The gel film is synthesized by acetobacter xylinum in situ in a fermentation medium containing polymyxin B and panax notoginseng saponins, the gel film is of a three-dimensional network structure, the polymyxin B and the panax notoginseng saponins are wrapped in a bacterial cellulose network, and the polymyxin B and the panax notoginseng saponins are evenly distributed in the bacterial cellulose network. And the fiber diameter of the gel film is 48.68 + / -5 nm. The prepared wound dressing has the wet adhesion characteristic and can effectively promote rapid and scar-free healing of chronic infectious wounds and large-area wounds, so that the method is expected to be widely applied to green synthesis of the wound dressing with antibacterial and wound healing promoting functions, and a new form is provided for use of the pseudo-ginseng powder and the polymyxin B.

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.

This invention relates to the field of biochemical technology, and particularly to highly specific haptens of polymyxin B and colistin, artificial antigens, their preparation methods, and applications. The haptens have structures as shown in Formula I or Formula II. The applications include: (1) preparing specific antibodies against polymyxin B or colistin; (2) detecting specific antibodies against polymyxin B or colistin; and (3) preparing reagents for detecting specific antibodies against polymyxin B or colistin. This invention further provides artificial antigens obtained by conjugating the haptens with carrier proteins. Using the artificial antigens provided by this invention as immunogens to immunize experimental animals, highly specific and sensitive antiserum can be prepared, which can then be used to extract and prepare polyclonal antibodies. These methods can be used to establish highly specific, highly sensitive, simple, and rapid detection methods for polymyxin B and colistin, and have significant application value.

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.

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 discloses a polymyxin B modified cellulose-based liquid dressing as well as a preparation method and application thereof. According to the liquid dressing, polymyxin B modified cellulose particles are combined with a polyvinyl alcohol glycerol film forming system; a wet healing environment and a physical barrier are used for promoting wound regeneration, gram-negative bacterium infection is eliminated based on hydrogen-bond interaction and electrostatic interaction, strong bactericidal ability is achieved, and the killing rate of gram-negative bacteria under the minimum inhibitory concentration is larger than 99.9%. Besides, the liquid dressing has good viscosity and film-forming property, can form a film after being smeared on a wound for 3 minutes, and meets the requirements of protecting the wound and providing a suitable environment for promoting wound healing; and meanwhile, the device is easy to remove and does not damage new tissues. The problem of systemic toxicity exposure caused by application of polymyxin B to large-area wounds is solved, and an innovative solution is provided for solving wound infection and promoting wound healing.

The present invention provides a novel pharmaceutical composition of polymyxin B / trimethoprim and rifampicin, as well as a preparation method and topical ocular application thereof (e.g., treatment of ocular infections).

Antimicrobial peptide compounds, pharmaceutical compositions, and methods for their use in inhibiting microbial growth are provided. The methods provided include methods for inhibiting pan drug resistant Acinetobacter baumannii by administering the peptide compounds to a subject. A method is provided for inhibiting pan drug resistant Acinetobacter baumannii with a synergistic combination of peptide compound Acetyl-AS-aib-LRKL-aib-KRLL-amide (SEQ ID NO: 1) and polymyxin B. In other methods, peptide compounds are provided for inhibiting P. gingivalis which is the keystone bacteria of periodontal disease, the 6th most common infectious disease worldwide.

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.

The invention provides an antibacterial hydrogel wound dressing with a photothermal effect as well as a preparation method and application of the antibacterial hydrogel wound dressing, and aims to solve the problems that the traditional wound dressing is insufficient in antibacterial ability and limited in inhibition of drug-resistant bacteria, and the hydrogel prepared by the invention has good functions of resisting bacteria, drug-resistant bacteria, inflammation and oxidation and promoting wound healing. The preparation method comprises the following steps: synthesizing the silver-polydopamine nanoparticles, preparing an extracellular matrix hydrogel prepolymer, and combining the silver-polydopamine nanoparticles with the polymyxin B to form the final hydrogel. The hydrogel disclosed by the invention can realize sterilization treatment through a photothermal effect under the irradiation of near-infrared light, has relatively good biocompatibility, temperature-sensitive characteristic and wound healing promotion effect, and is suitable for treating a wound infected by drug-resistant pseudomonas aeruginosa. Experimental results show that the hydrogel disclosed by the invention has good mechanical properties, degradability and adhesion, and shows remarkable antibacterial and healing-promoting effects in vitro and in mouse models.

The invention belongs to the technical field of biology, and relates to application of a composition of caerin1.1 / 1.9, caerin1.1 / 1.9 and polymyxin B in treatment of drug-resistant acinetobacter baumannii infection. In the caerin1.1 / 1.9, the mass ratio of the caerin1.1 to the caerin1.9 is 1 to (1 to 3). In the composition, the mass ratio of the caerin1.1 / 1.9 to the polymyxin B is 1: (0.2-3). The amino acid sequences of the caerin1.9 of the caerin1.1 are as shown in SEQ ID No. 1 and SEQ ID No. 2 of the caerin1.1. The composition of the caerin1.1 / 1.9, the caerin1.1 / 1.9 and the polymyxin B plays a role in resisting carbapenem acinetobacter baumannii by reducing the biological membrane of the acinetobacter baumannii, down-regulating the expression of efflux pump genes adeA, adeB and adeC or increasing the pore number of a cell membrane.

The invention relates to application of cacumen biotae alcohol for reversing drug resistance of polymyxin. The application is realized through the function of the platycladol for inhibiting the MCR-1 enzyme, specifically, the combination of the platycladol and the polymyxin B can recover the bactericidal effect of the polymyxin B on the MCR-1 positive enterobacter, and the bactericidal effect is a synergistic effect. According to the combined medication scheme, host cells can be protected in a cell infection model, the death rate can be remarkably reduced in a mouse peritonitis infection model, and no obvious toxicity is observed in the treatment dosage of platycladi alcohol. The invention provides a therapeutic scheme for solving the problem of drug resistance of clinical polymyxin B mediated by MCR-1.

The invention belongs to the technical field of biological medicine, and particularly relates to an antibacterial composition for treating escherichia coli infection and a preparation method and application thereof. The antibacterial composition is prepared from TBP-TA and polymyxin B, wherein the TBP-TA and the polymyxin B have aggregation-induced emission characteristics; wherein the mass ratio of the polymyxin B to the TBP-TA is 1 to (1 to 32). The antibacterial composition provided by the invention can be used for treating gram-negative bacterium infection, and the antibacterial activity of PMB on gram-negative bacteria can be effectively improved.

The invention relates to the field of microorganisms, and discloses application of bacillus polymyxa and L-gamma-diaminobutyric acid in production of polymyxin B and a method for producing the polymyxin B. According to the method, through the synergistic effect of the bacillus polymyxa and the L-gamma-diaminobutyric acid, the yield of the polymyxin B is remarkably increased, non-target byproducts are reduced, and the large-scale production of the high-purity polymyxin B in medicine and animal husbandry is met.

The invention discloses a tobramycin polymyxin conjugated compound as well as a preparation method and application thereof. The tobramycin and polymyxin conjugated compound comprises tobramycin and polymyxin which are connected through a chemical bond, and specifically, the tobramycin and the polymyxin are connected through an amido bond or triazole. The tobramycin polymyxin conjugated compound disclosed by the invention can be used for efficiently killing persistent bacteria under the condition of independently using the tobramycin polymyxin conjugated compound; particularly, the modified tobramycin and polymyxin B are connected through an amido bond to obtain the compound AKPB1, high-retention-level mutant strains of escherichia coli can be efficiently killed under the condition of independent medication, the dosage is small, and the compound AKPB1 obviously has potential important application value in the aspect of clinical antibacterial infection treatment and has a broad application prospect. The compound is expected to be used for treating bacterial infection diseases including but not limited to pneumonia, blood flow infection, urinary tract infection, respiratory tract infection, intestinal infection and the like, and is expected to be used for treating bacterial infection of animals.

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.

The invention provides X-ray excited nano-particles with lipidosome coated with an organic photosensitizer. The nano-particles comprise polymyxin B, a lipidosome carrier, an X-ray sensitizer and the organic photosensitizer. The invention also provides a preparation method and application of the nanoparticles. The nano photosensitizer provided by the invention realizes efficient resistance to drug-resistant bacteria under low-dose irradiation, and can be used for deep tissue drug-resistant bacteria infection treatment.

This invention discloses an antimicrobial peptide, its composition, and its applications, belonging to the field of polypeptide pharmaceuticals. This antimicrobial peptide, by introducing groups containing fluorinated phenyl, chlorophenyl, and diaminobutyric acid to form an amphiphilic molecular conformation, possesses advantages such as good biocompatibility, high stability, low synthesis cost, and low likelihood of inducing drug resistance. Experiments show that the minimum inhibitory concentration (MIC) of this antimicrobial peptide against various Gram-negative bacteria is significantly lower than that of the traditional antibiotic polymyxin B and the control peptide D65. Furthermore, in a neutropenic mouse infection model, it can significantly reduce bacterial load, demonstrating superior antimicrobial activity. Simultaneously, the antimicrobial peptide exhibits lower toxicity to human renal proximal tubular epithelial cells compared to the traditional antibiotic polymyxin B and the control peptide D65. In summary, this antimicrobial peptide holds promise as a replacement for polymyxin B in the treatment of multidrug-resistant Gram-negative bacterial infections, and is suitable for the prevention and control of various infections of the respiratory system, urinary system, and skin and soft tissues.

The invention discloses a fermentation method for increasing the yield of polymyxin B. The fermentation method comprises the following steps that 1, bacillus polymyxa is inoculated into an initial culture medium containing Mg < 2 + > and Mn < 2 + > for fermentation, the concentration of Mg < 2 + > in the culture medium is 0.5-10 mM, and the concentration of Mn < 2 + > in the culture medium is 5-100 mu M; and step 2, sampling the fermentation liquor at set intervals, measuring the concentration of Mg < 2 + > / Mn < 2 + >, and supplementing a concentrated solution containing Mg < 2 + > and / or Mn < 2 + > into the fermentation liquor when the concentration of Mg < 2 + > is lower than a first threshold value and / or the concentration of Mn < 2 + > is lower than a second threshold value, so that the concentration of Mg < 2 + > in the fermentation liquor is maintained at 0.5-10mM, and the concentration of Mn < 2 + > is maintained at 5-100mu M. In the fermentation process of paenibacillus polymyxa, the concentration, the proportion and the adding time sequence of Mg < 2 + > and Mn < 2 + > ions in the culture medium are accurately controlled and optimized, the maximum catalytic efficiency of an NRPS enzyme system is met, and therefore synthesis of polymyxin B is efficiently driven.

The invention relates to the technical field of biomedicine, and provides application of combination of bacteriophage and antibiotic in preparation of a drug-resistant bacterial infection drug, the bacteriophage is acinetobacter baumannii or mycobacterium tuberculosis bacteriophage, and the antibiotic comprises one or more of amikacin, fosfomycin and polymyxin B. The invention provides the application of the combination of the bacteriophage and the antibiotic in the aspect of preparing the drug-resistant bacterial infection drug, the synergistic interaction can be realized, the drug resistance is reduced, the bacteriocidal spectrum is expanded, and the support is provided for the early intervention, accurate effect generation and prognosis improvement of the drug-resistant bacterial infection.