97 results about "Beta lactam antibiotic" patented technology

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 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.

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.

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.

The invention discloses a novel broad-spectrum beta-lactamase inhibitor. The structure of the compound is shown in the formula I, by means of research on activity of six beta-lactamases in four types with the compound, it is found that the compound can inhibit activity of multiple beta-lactamases, when the compound is combined with beta-lactam antibiotics, the combination has powerful growth inhibiting activity on bacteria generating beta-lactamase, it can be expected that a drug which can recover antibacterial activity of the beta-lactam antibiotics to treat and prevent infection caused by bacteria of animals including human can be developed, and the novel broad-spectrum beta-lactamase inhibitor has great social and economic benefits.

Broad spectrum beta-lactamase inhibitors. Certain inhibitors also exhibit potent antibiotic activity in addition to beta-lactamase inhibition. Compounds of the invention are designed such that on cleavage of the beta-lactam ring reactive moieties are generated which can inactivate beta-lactamase. Also provided are methods of making beta-lactamase inhibitors and beta-lactam antibiotics exhibiting such inhibition. Additionally provided are pharmaceutical compositions for treatment or prevention of bacterial infections and methods of treatment of such infections.

The invention discloses a method, a special kit and test paper strips for detecting beta-lactam antibiotics based on penicillin-binding protein. The receptor kit used for detecting beta-lactam antibiotics comprises: protein represented by SEQ ID NO: 1, enzyme labeled ampicillin and a standard substance solution, wherein the standard substance is penicillin G. The kit and colloidal gold test paper strips provided by the invention have advantages of high sensitivity, high accuracy, high precision, low cost, simple operation, short detection period, simple storage, and long shelf-life. The kit and colloidal gold test paper strips are suitable for various work units. With the kit and colloidal gold test paper strips, simultaneous and rapid detections of large batches of samples can be realized, and on-site high flux rapid detections can be realized. Therefore, the kit, the colloidal gold test paper strips and the method provided by the invention play an important role in the detections of beta-lactam antibiotics.

The invention discloses a kit test method of beta-lactam antibiotics residue in milk, comprising the following steps: performing once activation to bacillus stearothermophilus, then culturing the activated bacillus stearothermophilus in a production culture medium at 50-65 DEG C for 24-36h while stirring in a rotation speed of 100-150rpm, centrifugalizing to collect bacteria mire, adding agarose bromcresol purple solution, mixing evenly to ensure the number of spore in each kit reach 1.00*10<7>-2.50*10<8>cfu, subpackaging the spore in porous reaction vessels at 60-70 DEG C, covering aluminum-plastic film, placing upside down, sealing, placing the vessels in aluminum-plastic packages and storing in dark place while keeping from wet. The kit has the advantage of easy operation, high sensibility, good repeatability, low cost and high throughput, can be stored at 4-8 DEG C for 12-18 months and can be used to test beta-lactam antibiotics residue in milk.

The invention provides a hapten comprising a 6-[D-alpha-aminoacetamido]penicillin derivative crosslinked at the alpha-amino group with a substituted or unsubstituted phenyldicarbaldehyde. In addition, the invention provides an immunogen comprising the aforementioned hapten coupled to an antigenicity-conferring carrier material, a conjugate comprising the aforementioned hapten coupled to a labelling agent, as well as, antibodies raised against the aforementioned immunogen and capable of binding with at least one structural epitope of an intact beta-lactam ring. The invention further provides a method and a kit for detecting, or determining the quantity of, beta-lactam antibiotics, as well as, use of the aforementioned conjugate with the aforementioned antibodies for detecting, or determining the quantity of, beta-lactam antibiotics. The present invention has broad specificity across the main first generation beta-lactams and can be used to test milk and meat and the like for the presence of residual beta-lactam antibiotics.

The invention relates to synergistic dihydroarteannuin oxyethylimidazole derivatives and application thereof. The dihydroarteannuin oxyethylimidazole derivatives have the structure disclosed as one of Formulae I-III, and can be used for preparing an antimicrobial synergist for antibiotics. The dihydroarteannuin derivatives can inhibit growth of multidrug-resistant Escherichia coli when being used independently or combined with beta-lactam antibiotics, reverse the drug resistance of the antibacterial drug to bacteria, and enhance the antimicrobial efficacy of antibiotics.

Broad spectrum beta-lactamase inhibitors. Certain inhibitors also exhibit potent antibiotic activity in addition to beta-lactamase inhibition. Compounds of the invention are designed such that on cleavage of the beta-lactam ring reactive moieties are generated which can inactivate beta-lactamase. Also provided are methods of making beta-lactamase inhibitors and beta-lactam antibiotics exhibiting such inhibition. Additionally provided are pharmaceutical compositions for treatment or prevention of bacterial infections and methods of treatment of such infections.

The invention discloses a preparation method for ZCHH tablets and a method for reversing the drug tolerance of MRSA (Methicillin-Resistant Staphylococcus Aureus) by using ZCHH and an antibiotic together. The preparation method comprises the following steps: thoroughly mixing ZCHH with lactose according to the weight ratio of the ZCHH to the lactose of 40 to 9; preparing wet granules with starch slurry of 10%; treating the wet granules with a 16-mesh sieve; drying at 60-70 DEG C; after granule straightening, adding magnesium stearate of which the weight is 1% of that the granules to the granules; compressing to form the ZCHH tablets. The method for reversing the drug-tolerance of the MRSA by using the ZCHH and the antibiotic together comprises the following steps: MRSA strains are isolated clinically; only ZCHH as well as both ZCHH and a beta-lactam antibiotic are applied to in vitro bacteriostasis; only ZCHH as well as both ZCHH and a beta-lactam antibiotic are applied to in vivo bacteriostasis; the structural hierarchies of the cell walls and cell membranes of the MRSA bodies are observed; statistical analysis is performed on the in vivo and in vitro antibiosis effects of the ZCHH and the beta-lactam antibiotics which are used together. According to the invention, the dead zone of action mechanism that the drug tolerance of the MRSA is reversed through drug combination is filled up, and an important theoretical basis is provided for clinical medication.

The invention discloses an animal bifidobacterium and a composition thereof, and belongs to the technical field of microbe application. The preservation number of the animal bifidobacterium provided by the invention is CGMCC No.4521 and is preserved in General Microbiology Center of Chinese Culture Collection Committee in Beijing on December 29, 2010. The animal bifidobacterium provided by the invention has a symplastic growth effect on lactobacillus casei, streptococcus faecium and bacillus cereus and has tolerance on carbostyril, aminoglycoside and monocyclic beta-lactam antibiotics, and the animal bifidobacterium is suitable for use in food, drugs and / or health care products.

The invention discloses macrolactone compounds or salts of the macrolactone compounds, as well as a synthesis method, a pharmaceutical composition and application of the macrolactone compounds or salts. The invention provides a macrolactone compound 1, a macrolactone compound 1' or salts of the macrolactone compound 1 and the macrolactone compound 1', a pharmaceutical composition containing the macrolactone compound 1, the macrolactone compound 1' or the salts of the macrolactone compound 1 and the macrolactone compound 1' and application of the pharmaceutical composition in preparing a drug for inhibiting methicillin-resistant staphylococcus aureus. When one or more of the macrolactone compound 1, the macrolactone compound 1', the salt of the macrolactone compound 1 and the salt of the macrolactone compound 1' are jointly used in combination with beta-lactam antibiotics, the inhibiting effect of the beta-lactam antibiotics on the methicillin-resistant staphylococcus aureus can be obviously increased. The macrolactone compounds and the salts thereof are novel synergists having good in-vitro synergistic effect, can alleviate the drug resistance of the methicillin-resistant staphylococcus aureus to the beta-lactam antibiotic and are drug having good market development prospects.

The invention relates to a penicillin G acylase mutant constructed by genetic engineering. In comparison with wild type penicillin G acylase from achromobacter (Achromobacter sp.CCM 4824), the synthesis performance of the penicillin G acylase mutant is improved substantially, the maximum synthetic product / hydrolysate value S / H reaches 22.3 and is 3.9 times that of wild type enzyme, and various beta-lactam antibiotics can be efficiently synthesized catalytically. When the ratio of side chains to mother nucleus is 1.05:1, the conversion rate of the mother nucleus 6-APA, 7-ADCA, 7-ACCA and 7-APRA reaches 99.0% or above, and the penicillin G acylase mutant has wide industrial application prospects.

The present invention relates to pharmaceutical compositions of carbocephem antibiotics with β-lactamase inhibitors useful for the treatment of bacterial infections, in particular infections caused by bacteria that express β-lactamases as a mechanism of resistance to β-lactam antibiotics.

The invention belongs to the field of food detection and in particular relates to a kit for quantitatively detecting beta-lactamase residue in milk. The kit for quantitatively detecting beta-lactamase residue in milk is characterized in that the kit comprises an elisa plate enveloped with penicillin-binding proteins, marker coupled beta-lactam antibiotics, a skim milk powder freeze dried product of which the substrate reference 1 is beta-lactam antibiotics and which has the concentration of 0ppb, a skim milk powder freeze dried product of which the substrate reference 2 is beta-lactam antibiotics containing calibration concentration, and a beta-lactam antibiotic standard substance. The kit has high specificity and sensitivity, beta-lactam with the concentration of about 0.5U / ml can be detected, and the linear detection range is 1-16 U / ml; intra-batch CV percent of the kit is less than 10 percent, the inter-batch CV percent is less than 20 percent, and high precision is reflected; the detection steps are simple, the time consumption is low, and the cost is low; according to the kit, the beta-lactamase residue can be accurately, quantitatively and rapidly detected at high throughput, and the requirements of enterprises and detection mechanisms are met.

The invention discloses a PBP-1A affinity beta-lactam antibiotic electrochemical biological sensor, and a making method and an application thereof. The electrochemical biological sensor is characterized in that the surface of a glassy carbon electrode is commonly modified by graphene, penicillin G and nafion. The making method comprises the steps of bare electrode polishing, cleaning and activating, and concretely comprises: sequentially adding graphene and penicillin G to the surface of the glassy carbon electrode in a dropwise manner, well mixing, carrying out blow drying at 37DEG C, adding nafion in a dropwise manner, naturally air-drying the surface, immersing the electrode in 5wt% bovine serum albumin, placing the immersed electrode in an oven, drying at 37DEG C for 30min, taking out the electrode, washing the electrode with a PBS solution to obtain a glassy carbon electrode with the surface modified by graphene-penicillin G-nafion as a work electrode, placing the work electrode in a system solution, carrying out DPV detection, and determining the concentration of beta-lactam antibiotics in a sample to be detected according to a standard curve. The electrochemical biological sensor has the advantages of high sensitivity, fast detection speed, low detection limit, high efficiency and cheapness.

The invention relates to the field of medicaments and provides a detection method for beta-lactamase. The detection method comprises the following steps of: culturing a sample which may contain microorganisms for 2 to 24 hours; and performing beta-lactamase detection on the sample by a chromogenic cephalosporin method. The invention also provides a method for detecting substrate characteristics of the beta-lactamase based on a substrate advantage combination principle. The method of the invention can not only judge whether the sample contains bacteria for producing the beta-lactamase rapidly,but also judge the medicament resistance of the bacteria to beta-lactam antibiotics. The invention also provides detection test paper for the beta-lactamase and a kit comprising the test paper. Compared with the prior art, the detection method and the detection test paper of the invention have the advantages that: the operation is simple and convenient, the detection speed is high, the response is sensitive and the result is stable; therefore, the detection method and the detection test have an extensive clinical application prospect.

The invention relates to the filed of drug detection, and particularly relates to a method and system for detecting drug resistance of beta-lactam antibiotics and application of beta-lactam antibiotics. The method comprises steps of mixing turbid liquid of microorganism to be tested with standard liquid of beta-lactam antibiotics, then removing the microorganism to be tested so as to obtain the liquid to be tested; obtaining liquid chromatogram of the liquid to be tested; judging the tolerance of the microorganism to be tested to the beta-lactam antibiotic according to the liquid chromatogram. The detection is not affected by concentration and purity of the microorganism and operation technique of an operator, so that the method has the advantages of high sensitivity, high accuracy, high detection speed and short detection time, and can be implemented within two hours. The detection method uses fewer microorganisms, does not need subculture for many times, greatly shortens the time of the whole experiment, provides prompt basis for rapid and early clinical drug use, especially for seriously infected patients; and since the detection time is greatly shortened, the consumable cost is low.

The invention provides a high-affinity penicillin binding protein. The invention is characterized in that the high-affinity penicillin binding protein is obtained by respectively transforming isoleucine 526 and glutamine 547 in a streptococcus agalactiae penicillin binding protein (PBP 1b) into lysine and arginine, so that the affinity of beta-lactam antibiotics is improved. The invention furtherprovides a quick detection test strip produced based on the protein, which can be used for quickly detecting beta-lactam antibiotic residues in agricultural and sideline products.

Broad spectrum beta-lactamase inhibitors. Certain inhibitors also exhibit potent antibiotic activity in addition to beta-lactamase inhibition. Compounds of the invention are designed such that on cleavage of the beta-lactam ring reactive moieties are generated which can inactivate beta-lactamase. Compounds of the invention include those of formula:and pharmacologically acceptable salts thereof where variables Z, Y, M, y, n, R, R4, R5, R1 and R2 are as defined in the specification. M most generally represents a chemical moiety which is in conjugation with the nitrogen of the core beta-lactam ring system of the compound, such that one or more reactive species, e.g., electrophilic or nucleophilic sites are generated on modification of M which is initiated by cleavage of the beta-lactam ring. Also provided are methods of making beta-lactamase inhibitors and beta-lactam antibiotics exhibiting such inhibition. Additionally provided are pharmaceutical compositions containing compounds of the invention for treatment or prevention of bacterial infections and methods of treatment of such infections employing such compounds.

The invention discloses a biomarker for forecasting severe drug-induced cutaneous adverse reaction of a child patient and an application. The biomarker is capable of forecasting the risk of severe cutaneous adverse reaction of the child patient using beta-lactam antibiotics such as penicillin, cephalosporin, carbamazepine, lamotrigine, oxcarbazepine, phenytoin, allopurinol, nevirapine, abacavir, methazolamide and dapsone.

A pharmaceutical composition for controlled drug delivery comprising a beta-lactam antibiotic or its pharmaceutically acceptable hydrates, salts or esters, and one or more carbomers. The above beta-lactam antibiotics formulation avoids the limitations of known beta-lactam controlled release form which are found to be either complex and / or cost-extensive to obtain requiring multiphase and / or selective coatings or fail to achieve the desired controlled release for once daily dosage form. Importantly, in the beta-lactam antibiotic form of the above the rate-controlling polymer wherein the Cmax of the formulation is substantially the same as that of a single dose of the immediate release formulation. Also advantageously the formulation achieves a rate controlling polymer wherein the T>MIC for the formulation is more than 17 hours when the MIC is 0.25 mcg / ml and more than 10 hours when the MIC is 2 mcg / ml. The above beta-lactam antibiotic form is thus directed to serve as the much desired simple and cost-effective controlled release form suitable for once daily administration.

The invention discloses a medical composite for treating livestock and poultry intestinal canal diseases and a preparation method and an application thereof, aiming at providing a medical composite and the preparation method and the application thereof, which can fast and effectively prevent and cure intestinal canal diseases. The composite comprises the following components in weight percent, 2%to 5% of pirquinozol antibiotics, 3% to 10% of beta-lactam antibiotics, 0.6% to 2% of beta-lactam inhibitor, 3% to 10% of aminoglycoside antibiotics and the balance auxiliary material acceptable in pharmacy. The pirquinozol antibiotics, such as norfloxacin lactate, is broad-spectrum antibiotics; the beta-lactam inhibitor has the functions of inhibiting enzyme and strengthening the effect; and thebeta-lactam antibiotics can destroy bacterial cell walls, which is favorable for aminoglycoside antibiotics to enter cells to take effect, increases the antibacterial effect and simultaneously enlarges the antibacterial spectrum. The composite of the invention can effectively cure canal diseases caused by Gram negative bacteria or anaerobe and the mixed infection of the Gram negative bacteria andthe anaerobe.

The present invention discloses isolation of Penicillin Acylase (PA) from Achromobacter sp CCM 4824 expressed in recombinant strain E. coli BL21 CCM 7394 bearing the recombinant plasmid pKXIP1 and processing of PA into biocatalyst useful for the industrial synthesis of antibiotics. More particularly the invention discloses a synthesis of semi-synthetic [beta]-lactam antibiotics in the reaction mixture consisting of activated acyl-donor (D-p-hydroxyphenylglycine methyl ester or amide for Amoxicillin and Cefadroxil; D-phenylglycine methyl ester or amide for Ampicillin and Cephalexin) and nucleophile (6-APA or 7-ADCA) catalyzed by PA obtained from recombinant E. coli BL21 CCM 7394 as the biocatalyst.

Broad spectrum beta-lactamase inhibitors. Certain inhibitors also exhibit potent antibiotic activity in addition to beta-lactamase inhibition. Compounds of the invention are designed such that on cleavage of the beta-lactam ring reactive moieties are generated which can inactivate beta-lactamase. Also provided are methods of making betalactamase inhibitors and beta-lactam antibiotics exhibiting such inhibition. Additionally provided are pharmaceutical compositions for treatment or prevention of bacterial infections and methods of treatment of such infections.

This invention relates to the crystallization of compounds, specifically involving beta-lactam antibiotics faropenem Na crystallization and its preparation method.