46 results about "Avibactam" patented technology

The invention relates to a method for synthesizing a beta-lactamase inhibitor Avibactam and belongs to the technical field of preparation of beta-lactamase inhibitors. The method disclosed by the invention comprises the following steps: (1) taking a compound 2 as a raw material, and reacting with R<1>NH2 so as to produce a compound 3; (2) enabling the compound 3 and a biocatalyst to produce a compound 4 in an organic solvent in the presence of glucose or sucrose; (3) enabling the compound 4 to react with trifluoroacetic anhydride so as to obtain a compound 5; (4) enabling the compound 5 to react with R<2>ONH2 so as to produce a compound 6; (5) hydrolyzing the compound 6 under alkaline conditions so as to produce a compound 7; (6) enabling the compound 7 to react with triphosgene so as to produce a compound 8; (7) enabling the compound 8 to react with ammonium formate in the presence of a catalyst so as to produce a compound 9 in the organic solvent, wherein the catalyst is a Pd/C system; and (8) enabling the compound 9 to react with a sulfonating agent, thereby obtaining the product 1. The method disclosed by the invention is stable in process, high in yield, simple and safe in operation and low in production cost.

The invention belongs to the technical field of medicines, relates to an antibiotic combination containing Avibactam and an application of the antibiotic combination, provides an application of Avibactam or pharmaceutically acceptable salt and carbapenems antibiotics to preparation of medicines for treating or preventing bacterial infection, particularly an application of the Avibactam to preparation of medicines for treating infection caused by escherichia coli, pseudomonas aeruginosa, klebsiella pneumoniae, baumanii and enterobacter aerogenes so as to solve the problem of drug resistance of the carbapenems antibiotics.

The invention provides a simple and convenient production method of avibactam. The simple and convenient production method of the avibactam comprises the steps of using piperidyl-5-keto-2S-formate IIas a raw material, making the piperidyl-5-keto-2S-formate II and O-protecting group hydroxylamine hydrochloride subjected to condensation reaction, and then obtaining 5R-substituted oxyaminopiperidyl-2S-formic acid V through reduction, chiral resolution and hydrolysis under an alkaline condition; and then making the 5R-substituted oxyamino piperidyl-2S-formic acid V and phosgene or triphosgene ordiphosgene subjected to cyclic urea reaction reaction, acylating chlorination reaction and amidation reaction through a one-pot method, obtaining {[(2S,5R)-2-formamyl-7-oxo-1,6-diazetidine[3.2.1]octane-6-yl]oxy}sulfonyl tetra-n-butylammonium salt VII through protecting group take-off, sulphating and tetrabutyl amination salification, and producing the avibactam I finally through ion exchange. Thesimple and convenient production method of the avibactam is simple and convenient in production route, easy to operate, low in raw material price, low in cost, small in three waste discharge, high inatom utilization rate, economical and environmentally friendly, and the yields of the various steps are high, so that the simple and convenient production method of the avibactam benefits industrial production of the avibactam.

The invention discloses a method for preparing amorphous avibactam sodium by spray-drying. According to the invention, solution of sodium iso-octoate is dropwise added into solution of avibactam tetrabutylammonium salt, after dropwise adding is completed, the reaction is performed for 3 to 4h, and purified water is added for extraction; after a water phase is subjected to spray-drying, the amorphous avibactam sodium is obtained. The method disclosed by the invention is simple in step and easy for industrial production, the purity of a product is greater than or equal to 98.0%, and yield is greater than or equal to 90.0%.

The invention discloses an avibactam and beta-lactam antibiotic compound synergistic composition which comprises avibactam and beta-lactam antibiotics, and the mass ratio of the avibactam to the beta-lactam antibiotics is 1: 80-40: 1. The avibactam and beta-lactam antibiotic compound composition disclosed by the invention has an obvious synergistic effect, overcomes and delays rapid degradation ofbetalactam antibiotics in plants, reduces the application dosage and frequency, and obviously improves the prevention and treatment effect on citrus yellow shoot.

The invention belongs to the technical field of medicines. The invention relates to an antibacterial composition containing avibactam and meropenem and application thereof. Particularly, the inventionprovides application of avibactam or a pharmaceutically acceptable salt thereof and meropenem in preparation of a medicine for treating or preventing bacterial infection, in particular to applicationin preparation of medicines for treating infection caused by escherichia coli, pseudomonas aeruginosa, klebsiella pneumoniae, acinetobacter baumannii and enterobacter aerogenes, and aims to solve theproblem of drug resistance of carbapenem antibiotics.

The invention belongs to the field of anti-infective medicines, and specifically discloses a cefepime and avibactam compound component for injection. The compound component is a mixture of cefepime and avibactam in a mass ratio of 8-1:1-8. The compound component has a good synergistic effect after mixing according to the above ratio, and the synergy rate of the cefepime and the avibactam is up to100%, which is better than other combinations; the sensitivity to drug-resistant bacteria can be significantly improved, MIC50 (>512 mcg/Ml) and MIC90 (>512 mcg/ml) of CRKP to the cefepime are reducedto MIC50 (4 mcg/ml) and MIC90 (32 mcg/ml), the activity is increased by 103 times and 16 times respectively, and the compound component greatly improves the effectiveness of drugs. Meanwhile, at least three molecules in the cefepime have tetravalent nitrogen atoms which can form zwitterions, the tissue distribution (especially brain tissues) is good, and the penetrating ability to an enterobacterium membrane is better than the same type of cephalosporin.

The invention provides a synthesis method of an avibactam intermediate (I). According to the method, an enamine substrate is subjected to asymmetric hydrogenation in an organic solvent in a hydrogen environment under the catalysis of a rhodium complex formed by a rhodium metal catalyst and a chiral diphosphine ligand to prepare the avibactam intermediate (I). The method has the advantages of mild reaction conditions, excellent enantioselectivity and diastereoselectivity, high chemical yield and potential industrial application value.

The invention discloses a preparation method of an avibactam intermediate. The method comprises the following step: performing a reaction on a compound I and trimethylsulfoxonium iodide in the presence of a base to prepare a compound II, wherein the structures of the compound I and the compound II are shown in the specification, R is one selected from the group consisting of methyl, ethyl, benzyl,tert-butyl and allyl, and the base is one or more selected from the group consisting of magnesium hydroxide, lithium hydroxide and calcium hydroxide. According to the preparation method of the avibactam intermediate, the method uses pyroglutamate with double protection as a raw material, the pyroglutamate reacts with the trimethylsulfoxonium iodide in the presence of the base to obtain the avibactam intermediate, and the method provided by the invention avoids the defects of potential safety hazard of a strong base, severe reaction condition requirements and strict process control requirements in the prior art, and has the advantages of mild reaction conditions, simple operation, high safety, and less reaction impurities.

The invention discloses a synthesis method of avibactam sodium. (2S,5R)-benzyloxyamino piperidine-2-ethyl formate oxalate (I) is used as an initial raw material; and the method comprises the followingsteps: reacting the raw material with a protecting group, carrying out carbonylation cyclization, carrying out hydrolysis of ester, ammoniating, sulfonating with a sulfur trioxide complex, salifyingwith an ammonium ion source, and salifying with a sodium salt to obtain avibactam sodium, and has the advantages of simple operation, easily controlled conditions, easy industrial production and wideapplication prospect.

The invention relates to a method for synthesizing an avibactam intermediate compound. The specific synthetic route of the method is as described in the specification. According to a technical schemeof the invention, no precious metal catalyst is used, and no heavy metal pollution is produced; high yield and low cost are realized; and the method is mild in reaction condition and friendly to environment, and can realize industrial production.

The present invention relates to avibactam free acid, a method for preparing avibactam free acid and a method for preparing avibactam sodium by further reacting avibactam free acid. The invention further refers to a pharmaceutical composition comprising avibactam free acid, one or more alkaline sodium salt(s) and one or more beta-lactam antibiotic(s). The pharmaceutical composition of the present invention can be used as medicament, in particular for treatment and/or prevention of bacterial infections.

The invention discloses a method for detecting the drug concentration of avibactam and ceftazidime in blood plasma, and belongs to the technical field of drug analysis. The method specifically comprises the following steps: taking pretreated blood plasma, separating a to-be-detected substance from a blood plasma matrix by utilizing ultra-high performance liquid chromatography, obtaining a mass-to-charge ratio of the to-be-detected substance to a corresponding isotope internal standard substance by virtue of mass spectrometry, and calculating the contents of avibactam and ceftazidime by utilizing an isotope internal standard quantification method according to an established calibration curve. The isotope internal standard substances are avibactam-13C5 and ceftazidime-d5. The method disclosed by the invention is high in sensitivity, strong in specificity, accurate and simple in pretreatment process; separation and detection of avibactam and ceftazidime drugs in blood plasma are completedwithin 5.0 min, the method can be used for quantitative analysis of avibactam and ceftazidime in blood plasma clinically, and the simple and rapid detection method is provided for concentration monitoring of avibactam and ceftazidime clinically.

The invention relates to an avibactam and cefmenoxime compound powder injection for injection and a preparation method thereof. The compound powder injection is prepared by well mixing cefmenoxime hydrochloride and avibactam sodium, tabletting and crushing. The powder injection disclosed by the invention is easy to disperse and dissolve when being prepared into an injection, is convenient to use, cannot easily generate beta-lactamase bacterial drug resistance while ensuring the content of cefmenoxime, and has a good market application prospect.