34 results about "Cefbuperazone" patented technology

The invention relates to a medicinal composition of cefoperazone sodium and tazobactam sodium. The medicinal composition comprises the following components in part by weight: 4 to 8 parts of cefoperazone sodium and 1 part of tazobactam sodium, wherein the tazobactam sodium is measured by a powder X-ray diffraction measuring method, and characteristic diffraction peaks are shown at the positions of 6.9 degrees, 10.5 degrees, 11.4 degrees, 16.6 degrees, 19.2 degrees, 22.7 degrees, 27.0 degrees, 29.7 degrees and 33.5 degrees in an X-ray powder diffraction map expressed by a diffraction angle of between 2 theta+/-0.2 degree. The medicinal composition has the advantages of high stability, low relevant substance content, controllable quality and the like, and the administration safety of patients is improved. The invention also relates to a method for preparing the tazobactam sodium with the technical characteristics of the characteristic diffraction peaks.

The invention relates to a synthesis method of cefbuperazone, and the synthesis method comprises the following steps: (1) protecting 7beta-amino-7alpha-methoxy-3-[(1-methyl-1H-tetrazol-5-yl)S-methyl]-3-cephalosporin-en-4-carboxylic acid diphenyl methyl ester (7-MAC) with an amino group protective agent to obtain 7-MAC silane; (2) reacting cefbuperazone lateral chain with a halide to obtain cefbuperazone lateral chain acyl halide; (3) reacting 7-MAC silane with cefbuperazone lateral chain acyl halide to obtain an intermediate product, namely cefbuperazone diphenyl methyl ester; and (4) removing the protective group from cefbuperazone diphenyl methyl ester to obtain cefbuperazone, wherein the amino group protective group is hexamethyl disilylamine, trimethyl chlorosilane, N,O-bis(trimethylsilyl) acetamide or N,N-bis(trimethylsilyl)-2,2,2-trifluoroacetamide. The synthesis method is easy for realization and has the advantages of simple and reasonable synthesis route design, mild reaction conditions, simple, safe and controllable reaction process and high yield of cefbuperazone, and the intermediate product is easy to separate and purify.

The invention discloses a composite pharmaceutical composition of cefoperazone sodium and tazobactam sodium. The composite pharmaceutical composition is an injection, and is prepared from the following components in parts by weight: 3.5-4.5 parts of cefoperazone sodium, 1 part of tazobactam sodium, 0.5-1 part of ambroxol hydrochloride, 0-6 parts of excipient, 0-10 parts of isotonic agent, 0-1 part of antioxidant, a proper amount of citric acid-sodium citrate and 20 parts of injection water. The composite preparation of the cefoperazone sodium and the tazobactam sodium disclosed by the invention is stable in quality and significant in curative effect, not only can three active ingredients be evenly mixed, but also the composite pharmaceutical composition is excellent in stability, good in solubleness and good in clinical use safety.

The invention discloses a cefoperazone sodium compound prepared by using the fluid mechanics principle. Research&Development and Industrialization Project of High-end Medical Product Refinement Crystallization Technologies wins the second prize of national scientific and technological progress in 2015, and the fluid mechanics principle crystallization technology belongs to one of the high-end medical product refinement crystallization technologies. The cefoperazone sodium compound is determined by using X-ray powder diffraction, and the main characteristic peaks represented by the diffraction angle 2 theta in a map are located at 10.25+/-0.2 degrees, 14.40+/-0.2 degrees, 18.51+/-0.2 degrees, 23.14+/-0.2 degrees, 29.10+/-0.2 degrees, 33.25+/-0.2 degrees and 38.45+/-0.2 degrees. Cefoperazone acid reacts with a salt forming agent, and the cefoperazone sodium compound is prepared through secondary crystallization. The operation is simple, reactants are easy to obtain, the reaction condition is mild, and the yield is high. The compound is high in purity, low in impurity content, good in fluidity and good in stability. Meanwhile, the invention further discloses a preparation prepared from cefoperazone sodium, namely, cefoperazone sodium for injection. The preparation process of the preparation is simple, no excipient is needed, and the preparation has better stability and few side effects.

The invention provides a preparation method for injection cefoperazone sodium tazobactam sodium composition. The preparation method comprises the following steps of: crushing the cefoperazone sodium and the tazobactam sodium; and mixing the cefoperazone sodium and the tazobactam sodium in a weight ratio of 4:1; and separately packaging, pressing and capping the mixture. The preparation method is characterized in that the fineness of pulverization of the cefoperazone sodium and the tazobactam sodium is 50-120 meshes.

The invention discloses a method for preparing 4-ethyl-2,3-dioxypiperazine-1-formate. In the method, 1-ethyl-2,3-dioxypiperazine and chloro-formate are used as raw materials and reacted in an organic solvent system in the presence of an acid binding agent to form 4-ethyl-2,3-dioxypiperazine-1-formate, wherein the molar ratio of the 1-ethyl-2,3-dioxypiperazine to the acid binding agent to the chloro-formate is 1:1.0-3.0:1.0-2.0; the chloro-formate is methyl chloroformate or ethyl chloroformate; and the 4-ethyl-2,3-dioxypiperazine-1-formate is 4-ethyl-2,3-dioxypiperazine-1-methyl formate or 4-ethyl-2,3-dioxypiperazine-1-ethyl formate. The method greatly reduces cost, simplifies process, reduces byproducts, improves product purity and reduces solvent separation processes; and the prepared product can be used as an intermediate for piperacillin and cefoperazone and is suitable for industrial production.

The invention provides a cefoperazone sodium and sulbactam sodium composition, which comprises the following raw materials in parts by weight: 9-10 parts of cefoperazone sodium, 1 part of sulbactam sodium and 0.05-0.07 part of glutathione. The glutathione is added to the composition, so that the composition has relatively good antibacterial effect. Furthermore, a little of sulbactam sodium is utilized, so that accumulation of the sulbactam sodium in a body is reduced; and the production cost is reduced. In addition, by a novel sulbactam sodium crystal, the composition provided by the invention has relatively good stability.

The invention relates to a method for synthesizing 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride, which comprises the following steps: using 4-ethyl-2, 3-dioxopiperazine as a starting raw material, di-(trichloromethyl) carbonate as a formyl chloridizing reagent, trimethyl chlorosilane as an activator and a prptectant, triethylamine as an acid-binding agent and a catalyst which are reacted with each other to prepare the 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride; and adding crystallizing agents such as n-hexane, petroleum ether, hexamethyl disiloxane, dipropyl ether, cyclohexane into a reaction liquid of the 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride to separate out 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride crystal. The method for synthesizing and crystallizing the 4-ethyl-(2, 3-dioxo)-1-piperazine formyl chloride provides a more appropriate intermediate for producing piperacillin and cefoperazone, and can shorten the synthesizing process and improve the quality thereof.

The invention discloses a preparation method of cefoperazone acid, and belongs to the field of preparation of medicinal intermediates. The preparation method comprises the following steps: a precipitating agent is added to a solution of cefoperazone sodium used as a raw material in order to decolorize the solution, a dispersant is added to the decolorized solution, and crystallization is carried out to obtain the cefoperazone acid. The method allows the cefoperazone sodium which does not meet quality standards to be fully recycled, the prepared cefoperazone acid has the advantages of high content, few impurities and good stability, and the preparation method has the advantages of simplicity, energy saving and environmental protection, and is suitable for large-scale industrial production.

The invention provides a preparation method for cefbuperazone. The preparation method comprises the steps of performing an acylchloriration reaction on D-alpha-(4-ethyl-2 ,3-dioxo-piperazine-carboxamido)-beta-(S) hydroxybutyric acid and oxalyl chloride in the presence of copper toluenesulfonate at a temperature of 5 DEG C; then distilling a reaction product under a reduced pressure after the acylchloriration reaction; adding methylene dichloride; and distilling again under the reduced pressure. The preparation method for the cefbuperazone can increase a conversion rate of intermediate products and improve purity of a final product of the cefbuperazone.

The invention relates to a preparation method of a cefbuperazone side chain; and the cefbuperazone side chain is obtained by synthesizing two raw materials of D-threonine and DEPT through two-step reaction. According to the invention, reaction steps comprise cefbuperazone side chain synthesis and reaction liquid after treatment. According to the invention, in the after treatment process, crystallization of an extracting liquor uses a pH value controlling crystallization method, so that a concentrating link is omitted; and the invention is to provide a cefbuperazone immediate, which is prepared by simple technical steps and is suitable for industrial production.

The invention discloses a synthetic method of a cefbuperazone intermediate, belonging to the technical field of chemical synthesis. The cefbuperazone intermediate is prepared by virtue of direct reaction of D-threonine and N-ethyl-2,3-dioxopiperazinyl formyl chloride in an alkali solvent at the room temperature. The synthetic method has the beneficial effects that the synthesis can be finished only through one step, has low reaction requirements and can be carried out at the room temperature; optimally, a reaction solvent is dichloromethane and can be taken as a later-period purification solvent, so that the cost is saved; the yield is high, and the product purity can reach 99.8%; and the operation is simple, the preparation is convenient, the cost is low, and the synthetic method is applicable to large-scale industrial production.

The invention relates to a refining method to prepare cefbuperazone intermediate compound with formulaI, aiming at providing a method to replace current column chromatography method to prepare cefbuperazone intermediate compound for economic and large-scale production. Cefbuperazone intermediate compound with formulaI is refined in isopropanol and highly pure product is obtained after separation process. Sodium salt of cefbuperazone is an antibiotic for cephamycins.

The invention relates to a preparation method of cefoperazone acid. The preparation method comprises the following steps: (1) in a dichloromethane system, allowing 7-TMCA to react with a silanizationreagent at 20-70 DEG C, and carrying out silanization protection on the amino group and the carboxyl group; (2) in a dichloromethane body and a DMA system, allowing HO-EPCP salt to react with ethyl chloroformate at the reaction temperature of 20-70 DEG C under the action of a catalyst to prepare mixed anhydride; (3) adding the 7-TMCA after silanization protection into the mixed anhydride, reactingat 20-70 DEG C to obtain a reaction solution; (4) hydrolyzing the reaction solution, adding alkali to adjust the pH to be 5.5-7.5, layering, adding solvent into the water phase, adding acid to adjustthe pH to be 1.5-2.5, crystalizing and filtering to obtain cefoperazone acid. The method disclosed by the invention has the advantages that the product yield can be improved, S-isomer can be reduced,the residual solvent is reduced, the solvent is easy to recycle, the wastewater does not contain phosphorus and is easy to process.

The invention provides a cefoperazone sodium composition freeze-dried powder for injection, and belongs to the field of medicine and medicine preparation technology. The cefoperazone sodium composition freeze-dried powder comprises following raw material ingredients, by weight, 7.26 to 9.17 parts of cefoperazone sodium, 4.36 to 5.50 parts of chitosan nanoparticle, and 84.38 to 89.10 parts of injection water. Advantages of the cefoperazone sodium composition freeze-dried powder are that: 1) antibacterial activity of the cefoperazone sodium composition is increased significantly; 2) antibacterial spectrum is widened, and drug tolerance is reduced greatly; 3) improvement of activity is capable of shortening medication cycle of patients, and reducing occurrence likelihood of adverse reaction caused by accumulation of cefoperazone sodium; and 4) the chitosan nanoparticle can be used as a freeze-dried skeleton agent of the freeze-dried powder injection instead of mannitol, so that active effects of mannitol on human bodies are avoided.

A cefbuperazone pharmaceutical composition has the advantages of high uniformity, strong anti-layering performance, fast dissolving rate and good fluidity. A product obtained by packaging is accord with pharmacopeia index requirements about powder injection bottle weight difference, solution clarity and the like.

The invention discloses a stable compound preparation of cefoperazone-piperacillin clavulanate drug, which is comprised by cefoperazone acid, piperacillin clavulanate and latent solvent, which weight ratio is 16~1:1:8.8~0.06. The latent solvent is preferred selected from sodium carbonate and sodium bicarbonate. Related substances content of the compound preparation, labelled content of the cefoperazone acid and the piperacillin clavulanate in the invention do not change much in influencing factor test, long-term sample tests and accelerated test in 40 DEG C. which accord with the standard of pharmacopoeia with stable product quality.