11 results about "Phosphonomycin" patented technology

The utility model discloses a raw material particle mixing device, and particularly relates to the technical field of fosfomycin tromethamine production mixing, the raw material particle mixing device comprises a mixing cylinder, the top end of the mixing cylinder is fixedly provided with a fixing ring, the surface of the fixing ring is detachably provided with a sealing plate through a plurality of bolts, the sealing plate is provided with a driving motor, and the driving motor is connected with the fixing ring. A stirring shaft is arranged at the output end of the driving motor, a plurality of telescopic stirring blade structures are fixedly arranged on the outer wall of the stirring shaft, each telescopic stirring blade structure comprises an outer pipe, one end of each outer pipe is fixedly mounted on the outer wall of the stirring shaft, an inner rod is slidably arranged in each outer pipe, and a concave block is fixedly arranged at one end of each inner rod. According to the utility model, the mixing range of raw materials in the mixing barrel can be enlarged, so that the mixing effect is improved, the caked raw materials and attachments on the inner wall of the mixing barrel can be beaten, uniform mixing of particles is promoted, residues on the wall of the barrel can be vibrated off after discharging, and the use effect is improved.

The application relates to the technical field of compound preparation, and discloses a synthesis method of fosfomycin intermediate levofosfoxacin salt, which comprises the following steps: taking propynol as raw material, performing esterification reaction, adding Pt / C, Cu (II) EDTA and hydrogen into the obtained reaction solution to prepare a cis-propenyl dichloro oxygen phosphorus solution, adjusting the pH of the reaction solution by using ammonia gas after hydrolysis, and performing salt reaction and epoxidation by using R- (+) -alpha-phenylethylamine to obtain the product after post-treatment. The propynol is not hydrolyzed after esterification, so that the impurity propadienyl phosphate is reduced; the later hydrogenation can obtain higher-purity cis-propenyl phosphate; the step of hydrolysis after esterification is reduced, a large amount of water does not need to be distilled and concentrated, and energy consumption is reduced; the reaction temperature and hydrogen pressure in the hydrogenation step are both low, and the reaction safety is high; R- (+) -alpha-phenylethylamine is used in the epoxidation stage, so that the splitting operation is not needed, and the process is simplified; the solvents can be recycled and reused, and the method is environment-friendly.

This invention discloses a method for detecting genotoxic impurities in fosfomycin calcium. The method involves preparing a test solution and a reference solution using hydrochloric acid as a solvent, and then detecting the test solution and reference solution using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS) to obtain the content of genotoxic impurities in fosfomycin calcium. The genotoxic impurities are: 1,2-epoxypropyl diethyl phosphate, (2-propenyl)-diethyl phosphate, allyl diethyl phosphate, and propyl diethyl phosphate. This invention develops an analytical method capable of simultaneously detecting four diethyl phosphonate genotoxic impurities in fosfomycin calcium. This method exhibits good specificity, injection precision, linear range, limit of quantitation, limit of detection, accuracy, repeatability, intermediate precision, and robustness. It can be used for the detection and monitoring of diethyl phosphonate impurities in fosfomycin calcium raw materials, ensuring product quality and improving the safety of clinical medication.

The invention relates to the field of medicines, and also relates to a fosfomycin-containing preparation intermediate and a use method thereof. According to the preparation intermediate obtained by the invention, the brittleness of the material can be reduced, the plasticity of the material can be improved, a product with uniform particle size distribution of the material is obtained, and samples with different particle size distribution ranges can be obtained by adjusting spray drying parameters or pulverizer parameters according to requirements. Meanwhile, in research, unexpected discovery shows that the impurity level of the sample prepared by the technical scheme provided by the invention is lower, and particularly, the impurity level is basically not increased in a long-time crushing treatment process by adopting a crusher.

The invention relates to a method for synthesizing cis-propenylphosphonic acid through a continuous flow hydrogenation reaction catalyzed by porous organic polymer supported palladium, and belongs to the technical field of synthesis of medical intermediates. According to the method, allene phosphonic acid is taken as a raw material, porous organic polymer supported palladium is taken as a catalyst, cis-propenylphosphonic acid is synthesized through continuous hydrogenation reaction in a micropacked bed reactor, the reaction temperature is 10-70 DEG C, the hydrogen pressure is 0.1-0.5 MPa, the reaction conversion rate can reach 99%, the reaction selectivity can reach 88%, and the activity of the catalyst is not obviously reduced after continuous reaction for 300 hours. According to the synthesis method provided by the invention, by virtue of the micro-packed bed reactor, the reaction speed is high, the safety is high, the reaction selectivity is good, continuous production of cis-propenylphosphonic acid can be realized, and the production cost of fosfomycin is reduced.

The invention provides a fosfomycin sodium composition and a preparation method thereof, and particularly relates to the field of medicines. Comprising freeze-dried powder prepared from fosfomycin sodium and metronidazole lipid microspheres, the mass of the freeze-dried powder containing fosfomycin sodium is 0.09-1.01 g, the mass of the metronidazole lipid microspheres is 145-155 mg, the mass of metronidazole contained in the metronidazole lipid microspheres is 50 mg, and the pH value of the freeze-dried powder dissolved in 5 ml of water at the temperature of 25-35 DEG C is 6.0-6.5. Different from traditional single-variety drug combination, metronidazole is lipid microspheres, so that the bioavailability of metronidazole can be improved; the medicine and fosfomycin sodium are jointly filled into the same penicillin bottle, so that clinical medication is facilitated.

The utility model provides a reaction device for preparing fosfomycin tromethamine, and particularly relates to the technical field of pharmaceutical production, the reaction device comprises a tank body, a feed port and a discharge port are respectively arranged at the upper end and the lower end of the tank body, an interlayer is arranged outside the tank body, a plurality of partition plates are vertically arranged in the interlayer, and the partition plates divide the interlayer into a plurality of cavities; a first outlet and a second outlet are respectively formed in the lower sides of two adjacent cavities; a first inlet and a second inlet are respectively formed in the upper sides of the two cavities adjacent to the first outlet and the second outlet; in the anticlockwise direction of the first inlet, each cavity is provided with a plurality of first flow guide pipes at intervals, and every two spaced partition plates are connected through the corresponding first flow guide pipe; in the clockwise direction of the second inlet, each cavity is provided with a plurality of second flow guide pipes at intervals, and every two spaced partition plates are connected in a penetrating mode through the corresponding second flow guide pipes. According to the utility model, the heating efficiency can be improved, and the heating uniformity can be improved.

This invention discloses a low-cost method for preparing fosfomycin levophosphoric acid salt, an intermediate of fosfomycin, comprising the following steps: (1) dissolving propylene phosphoric acid in a polar solvent; (2) adding a catalyst to the solution obtained in step (1); (3) adding alkali to the reaction solution obtained in step (2) to adjust the pH value, and then introducing hydrogen gas to carry out a hydrogenation reaction, reducing the terminal olefin to obtain cis-propylene phosphoric acid; (4) directly using the cis-propylene phosphoric acid solution obtained in step (3) for the epoxidation reaction in step (5) or performing the epoxidation reaction in step (5) after solvent replacement; (5) adding (R)-(+)-1-phenylethylamine to the cis-propylene phosphoric acid solution to adjust the pH, adding sodium tungstate and ethylenediaminetetraacetic acid, heating, adding hydrogen peroxide dropwise, maintaining the temperature after the dropwise addition to carry out the epoxidation reaction, cooling after the reaction, stirring, and filtering to obtain fosfomycin levophosphoric acid salt. This invention reduces costs and improves yield.

This invention discloses a lyophilized formulation of fosfomycin sodium for injection and its preparation method. The lyophilized formulation comprises fosfomycin sodium, L-histidine, trehalose dihydrate, glycine, and disodium edetate, wherein L-histidine serves as a buffer component, trehalose dihydrate serves as an amorphous matrix protectant, glycine serves as a crystalline framework agent, and disodium edetate serves as a metal ion chelating agent. The preparation method includes solution preparation, pH adjustment and fine filtration, pre-freezing and annealing, primary drying, secondary drying, and nitrogen sealing. This invention, through the synergistic combination of quaternary excipients, specifically solves multiple technical problems in the fosfomycin sodium system, such as epoxy hydrolysis degradation, difficulties in lyophilization due to high sodium content, and extreme hygroscopicity. The resulting lyophilized formulation exhibits intact appearance, rapid reconstitution, and good stability.

The utility model provides a stirring device for preparing fosfomycin tromethamine, and particularly relates to the technical field of pharmaceutical production, a motor for driving is arranged at the upper end of a tank body, a stirring shaft is arranged in the tank body, the upper end of the stirring shaft is connected with a driving shaft of the motor, and the stirring shaft is formed by combining a first rotating shaft, a second rotating shaft, a third rotating shaft and a fourth rotating shaft; the upper end of the first rotating shaft is connected with a driving shaft of the motor; guide grooves are formed in the upper ends of the second rotating shaft, the third rotating shaft and the fourth rotating shaft; guide shafts are arranged at the lower ends of the second rotating shaft, the third rotating shaft and the fourth rotating shaft; the cross sections of the guide groove and the guide shaft are regular triangles or regular quadrangles or regular hexagons, the guide shaft is embedded into the guide groove, and the first rotating shaft, the second rotating shaft, the third rotating shaft and the fourth rotating shaft are sequentially connected end to end; and connecting gaps among the first rotating shaft, the second rotating shaft, the third rotating shaft and the fourth rotating shaft are enclosed by the hoop. The stirring device is convenient to adjust to meet different types of stirring requirements.

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.