403 results about "Beta-lactamase" patented technology

This invention discloses and claims methods for inhibiting bacterial β-lactamases and treating bacterial infections by inhibiting bacterial β-lactamases in man or an animal comprising administering a therapeutically effective amount to said man or said animal of a compound, or pharmaceutically acceptable salt thereof, of formula (I) either alone or in combination with a β-lactamine antibiotic wherein said combination can be administered separately, together or spaced out over time. Pharmaceutical compositions comprising a compound of formula (I), or a combination of a compound of formula (I) and a therapeutically effective amount of a β-lactamine antibiotic, and a pharmaceutically acceptable carrier are also disclosed and claimed.

Described herein are compounds and compositions that modulate the activity of beta-lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.

Disclosed herein are α-aminoboronic acids and their derivatives which act as inhibitors of beta-lactamases. Also disclosed herein are pharmaceutical compositions comprising α-aminoboronic acids and methods of use thereof.

Disclosed herein are α-aminoboronic acids and their derivatives which act as inhibitors of beta-lactamases. Also disclosed herein are pharmaceutical compositions comprising α-aminoboronic acids and methods of use thereof.

A pharmaceutically composition, comprising a combination of an antibiotically active compound of the formula (I): with a β-lactamase inhibitor of one of the formulae (II) to (XIII) are active against Gram-negative bacteria, in particular such bacteria which have become resistant against antibiotics such as aztreonam, carumonam and tigemonam. Optionally the compositions may comprise another β-lactamase inhibitor of one of the formulae (II) to (XIII), particularly of formula (V) or formula (VI).

Substituted bicyclic beta-lactams of Formula I: (I), are β-lactamase inhibitors, wherein a, X, R1 and R2 are defined herein. The compounds and pharmaceutically acceptable salts thereof are useful in the treatment of bacterial infections in combination with β-lactam antibiotics. In particular, the compounds can be employed with a β-lactam antibiotics (e.g., imipenem, piperacillin, or ceftazidime) against microorganisms resistant to β-lactam antibiotics due to the presence of the β-lactamases.

Class A beta-lactamase may be used for reducing side-effects in the intestine associated with antibiotic therapy with a combination of beta-lactam antibiotic and beta-lactamase inhibitor.

β-Lactamase inhibitor compounds (BLIs) are disclosed, including compounds that have activity against class A, class C or class D β-lactamases. Methods of manufacturing the BLIs, and uses of the compounds in the preparation of pharmaceutical compositions and antibacterial applications are also disclosed.

A process for the preparation of alkyl esters of N-protected oxo-azacycloalkylcarboxylic acids of Formula III: comprises contacting a ketosulfoxonium ylide of Formula II: with an iridium catalyst to obtain Compound III, wherein PG1 is an amine protective group; k is 0, 1, or 2; and RU, R1, R2, and R3 are defined herein. An embodiment of the process further com rises contacting a compound of Formula I: with a sulfoxonium halide of formula (RU)3S(O)Z, wherein Z is halide, in the presence of a strong base to obtain Compound II. Additional embodiments add a series of process steps leading to the synthesis of 7-oxo-1,6-diazabicyclo[3.2.1]octanes suitable for use as β-lactamase inhibitors.

The invention relates to targeted post translational modifi-cation of metallo-beta-lactamase by truncation and inser-tion of a dipeptide at the amino terminal end to reduce amino terminal heterogeneity in a recombinant DNA pro-duction system. A protein K-T-E-ΔBL is expressed, and modified by host proteases to E-ΔBL. Appropriate nucleotide molecules, vectors and hosts are also de-scribed. E-ΔBL is useful in a pharmaceutical composition for treating antibiotic induced adverse effects in the intes-tine of patients treated with beta-lactam antibiotics.

A compound anti-beta-lactamase antibiotic is prepared from cefuroxime or its salt, sulbactam or its salt, and tazobactan or its salt. Its advantages are broad spectrum and high antibacterial effect.

The invention discloses a construction method of a penicillin-producing recombined strain of streptomyces virginiae IBL14. The method involves sequence properties of a beta-lactamase gene containing hydrolysis penicillin and gene clusters producing penicillin, and the whole process of a construction method of the penicillin-producing recombined strain constructed on this basis. Related genes are compiled through the penicillin-producing gene and the CRISPR-Cas I-B gene of streptomyces virginiae IBL14, and therefore the aim of increasing the penicillin yield is achieved. A new route and method are provided for increasing the types of biological medicine, improving the production level and improving the product quality.

A lateral flow chromatographic assay format for the performance of rapid enzyme-driven assays is described. A combination of components necessary to elicit a specific enzyme reaction, which are either absent from the intended sample or insufficiently present therein to permit completion of the desired reaction, are predeposited as substrate in dry form together with ingredients necessary to produce a desired color upon occurrence of the desired reaction. The strip is equipped with a sample pad placed ahead of the substrate deposit in the flowstream, to which liquid sample is applied. The sample flows from the sample pad into the substrate zone where it immediately reconstitutes the dried ingredients while also intimately mixing with them and reacting with them at the fluid front. The fluid front moves rapidly into the final “read zone” wherein the color developed is read against predetermined color standards for the desired reaction. Pretreatment pads for the sample, as needed, (e.g. a lysing pad for lysing red blood cells in whole blood) are placed in front of the sample pad in the flow path as appropriate. The assay in the format of the invention is faster and easier to perform than analogous wet chemistry assays.Specific assays for glucose-6-phosphate dehydrogenase (“G-6PD”), total serum cholesterol, β-lactamase activity and peroxidase activity are disclosed.

A pharmaceutical composition comprising: at least one aminoglycoside antibiotic and (a) at least one ion chelating agent used for inhibiting particulate formation, or (b) at least one buffer, or (c) at least one ion chelating agents and at least one buffer simultaneously. The composition for use in controlling microbial infection can be formulated into a solution, or combined with at least one beta-lactam antibiotic, or combined with at least one of beta-lactam antibiotic and at least one beta-lactamase inhibitor into a solution in a container.

The invention provides a stable-content drug compound containing Beta-lactamases inhibitors and piperacillin sodium and the preparation method thereof. The drug compound consists of piperacillin sodium, Beta-lactamases inhibitors and pH-value regulators with the weight proportion of 1 to 100:1:0.001 to 2. Diluted and delivered in any proportion with conventional clinical transfusions, the drug compound can have a stable piperacillin sodium content, dissolve rapidly, generate no crystallization or degradation products and receive no effect from the temperature. The preparation method of the stable-content drug compound containing Beta-lactamases inhibitors and piperacillin sodium has simple preparing method and high efficiency and is fit for a large-scale industrial production.

Disclosed herein are α-aminoboronic acids and their derivatives which act as inhibitors of beta-lactamases. Also disclosed herein are pharmaceutical compositions comprising α-aminoboronic acids and methods of use thereof.

The present invention provides a method in which cDNAs that encode signal sequences for secreted or membrane-associated proteins are isolated using a fusion protein that directs secretion of a molecule that provides antibiotic resistance, e.g., .beta.-lactamase. The present method allows the isolation of signal peptide-associated proteins that may be difficult to isolate with other techniques. Moreover, the present method is amenable to throughput screening techniques and automation, and especially in validating the presence of the signal sequence via expression of the protein in both prokaryotic and eukaryotic cells. This invention provides a powerful and approach to the large scale isolation of novel secreted proteins.

Described herein are compounds and compositions that modulate the activity of beta-lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.

A new antibacterially active agent has been isolated from Streptomyces clavuligerus. This new compound which is designated clavulanic acid has the formula (I):In addition to being a broad spectrum antibiotic of medium potency, clavulanic acid and its salts and esters have the ability to enhance the effectiveness of beta lactam antibiotics against many beta-lactamase producing bacteria.

Disclosed herein are α-aminoboronic acids and their derivatives which act as inhibitors of beta-lactamases. Also disclosed herein are pharmaceutical compositions comprising α-aminoboronic acids and methods of use thereof.

The present invention relates to pharmaceuticals and modified beta-lactamases. Specifically, the invention relates to novel recombinant beta-lactamases and pharmaceutical compositions comprising the beta-lactamases. Also, the present invention relates to methods for modifying a beta-lactamase, producing the beta-lactamase and treating or preventing beta-lactam antibiotic induced adverse effects. Furthermore, the present invention relates to the beta-lactamase for use as a medicament and to the use of the beta-lactamase in the manufacture of a medicament for treating or preventing beta-lactam antibiotics induced adverse effects.Still further, the invention relates to a polynucleotide and a host cell comprising the polynucleotide.

Described herein are compounds and compositions that modulate the activity of beta-lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.

Compounds of formula I: See Formula I in Figures Section wherein R1, R2, R3, R4 and n have any of the values defined in the specification, and their pharmaceutically acceptable salts, are useful for inhibiting simultaneously serine and metallo-β-lactamase enzymes, for enhancing the activity of β-lactam antibiotics, and for treating β-lactam resistant bacterial infections in a mammal. The invention also provides pharmaceutical compositions, processes for preparing compounds of formula I, and novel intermediates useful for the synthesis of compounds of formula I.

Fragment pairs of a Class A beta-lactamase (TEM-1 of E. coli) are disclosed that depend for their functional reassembly into the parent protein on the interaction of heterologous polypeptides or other molecules which have been genetically or chemically conjugated to the break-point termini of the fragment pairs. In addition, methods are provided for identifying fragment pairs that will optimally reassemble into a functional parent protein. Fragment pairs that comprise molecular interaction-dependent enzymes find use in (1) homogeneous assays and biosensors for any analyte having two or more independent binding sites, (2) tissue-localized activation of therapeutic and imaging reagents in vivo for early detection and treatment of cancer, chronic inflammation, atherosclerosis, amyloidosis, infection, transplant rejection, and other pathologies, (3 cell-based sensors for activation or inhibition of metabolic or signal transduction pathways for high-efficiency, high-throughput screening for agonists / antagonists of the target pathway, (4) high-throughput mapping of pair-wise protein-protein interactions within and between the proteomes of cells, tissues, and pathogenic organisms, (5) rapid selection of antibody fragments or other binding proteins which bind specifically to polypeptides of interest, (6) rapid antigen identification for anti-cell and anti-tissue antibodies, (7) rapid epitope identification for antibodies, (10) cell-based screens for high-throughput selection of inhibitors of any protein-protein interaction.

Described herein are compounds and compositions that modulate the activity of beta-lactamases and methods thereof. In some embodiments, the compounds described herein are biologically hydrolyzed to a beta-lactamase inhibitor. In certain embodiments, the compounds described herein are useful for the treatment of bacterial infections.