76 results about "Aminopenicillanic acid" patented technology

The invention relates to the field of pharmacy, and provides an improved method for preparing amoxicillin by an enzymic method, and a product obtained by the improved method for preparing amoxicillin by the enzymic method. The method comprises the following steps of: 1) dissolving 6-aminopenicillanic acid (6-APA) at the temperature of between 10 and 20 DEG C by using water or/and aqueous solution of ammonia which has the pH value of 7.0 to 8.0, and adding D-p-Hydroxyphenylglycine methyl ester hydrochlorid and penicillin G acyltransferase; 2) adjusting the pH value of a solution obtained in the step 1) to be 6.0 to 6.5, and reacting at the temperature of between 21 and 30 DEG C until the content of 6-APA is less than 5mg/ml to obtain a solution of an amoxicillin product; and 3) separating the penicillin G acyltransferase from the solution of the amoxicillin product, adjusting by using hydrochloric acid until the solution of the amoxicillin product is clarified, adding the aqueous solution of ammonia, adjusting the pH value to be 5.5 to 6.5, and crystallizing at the temperature of between 0 and 5 DEG C to obtain amoxicillin. By the improved method for preparing amoxicillin by the enzymic method, the quality of the amoxicillin product is greatly improved, and the medication safety of the amoxicillin product is further improved.

The invention discloses a process for preparing straight-through 6-aminopenicillanic acid, which comprises the following steps: a, filtering and acidizing penicillin fermentation solution, extracting the penicillin fermentation solution by using butanol, and concentrating and decoloring the extract to obtain butyl ester extracting solution of penicillin; b, back extracting the butyl ester extracting solution of the penicillin by using alkali solution to obtain brine solution of penicillin (heavy phase or RB for short); c, continuously injecting the brine solution of the penicillin into a degreasing tower in a vacuum pressure reduction state to convert the butyl ester into a gas phase from the brine solution of the penicillin, discharging the degreased brine solution of the penicillin out of a pressure reduction system from the bottom of the tower to a storage tank with a cooling device, and cooling the degreased brine solution of the penicillin for later use; and d, performing enzymatic conversion on the degreased brine solution of the penicillin, then adding 6-APA crystal seeds into the solution, growing the crystals, crystallizing the solution, and drying the crystals.

The invention discloses a process for preparing 6-aminopenicillanic acid, which comprises the following steps: (1) filtering the penicillin fermentation liquid, acidifying, extracting and concentrating with butanol, decoloring to obtain butyl extract of penicillin, (2) subjecting butyl extract of penicillin to back extraction with alkaline solvent, obtaining aqueous solution of penicillin salts, (3) degreasing the aqueous solution of penicillin salts, (4) loading the degreased aqueous solution of penicillin salts into penicillin acylated enzyme retort for enzyme conversion, charging 6-APA seeds, cultivating quartz, crystallizing and drying.

The invention discloses a synthesizing method of sulbactam acid. The method comprises the steps that: (1) under the existence of a strong acid, 6-aminopenicillanic acid, a diazotization reagent, and bromine or bromide are subjected to an insulation reaction in an organic solvent; excessive bromine is reduced; and a reaction product is extracted to a water layer; (2) an oxidant is dropped into the water-layer reaction product, and an insulation reaction is carried out; when the reaction is finished, a pH value is regulated; excessive potassium permanganate is reduced; an organic solvent is added, such that a reaction product is extracted to an organic solvent layer; (3) a catalyst is added into the organic-solvent layer product, such that hydrogenation bromine-removing is carried out; a reaction product is extracted to an organic-solvent layer; and distillation and crystallization are carried out. The organic solvent is ethyl acetate. According to the invention, ethyl acetate is adopted as the organic solvent in a four-step reaction, such that solvent consumption of the whole reaction is greatly reduced, and product total yield is effectively improved. With the method provided by the invention, by-product in the reaction can be comprehensively utilized, and advantages such as high yield, low cost, clean production, and the like are provided.

The invention relates to a method for recovering phenylacetic acid from waste liquid in preparation of 6-aminopenicillanic acid by an enzymic method. The method comprises the following steps: 1) using toluene to extract phenylacetic acid; 2) preparing a sodium phenylacetate aqueous solution with little impurity; and 3) using macroreticular resin for recovering phenylacetic acid from a water phase containing low-concentration phenylacetic acid. According to the invention, toluene is extracted from waste liquid in preparation of 6-aminopenicillanic acid by the enzymic method, a toluene phase containing phenylacetic acid and a water phase containing low-concentration phenylacetic acid are obtained; the toluene phase containing phenylacetic acid is extracted through alkali lye to obtain the sodium phenylacetate aqueous solution with high quality, the sodium phenylacetate aqueous solution can be directly used for producing penicillin through fermentation; the water phase containing low-concentration phenylacetic acid is pretreated for recovering sodium sulfate, macroreticular resin is used for absorbing phenylacetic acid for recovery, the low concentration water after adsorption can be directly discharged, zero discharge of phenylacetic acid can be almost realized, win-win of economy and environmental protection can be achieved, the by-product sodium sulfate can be used for fermentation, and also has economic benefit.

A process for recovering residual amounts of 6-APA, on the order of 10 g/L or less, from a predominantly aqueous liquor containing phenoxyacetic acid and less than about 2% organic solvents.

The invention discloses a method for preparing sulbactam and belongs to the technical field of pharmaceuticals. The method is characterized in that a 'one-pot' method is adopted, starting from 6-aminopenicillanic acid (6-APA), under the action of sodium nitrite and hydrobromic acid, a reaction solution which contains product 6 alpha-penicillanic acid is obtained through bromination reaction, and then, solid sulbactam is obtained through further oxidation and reduction reaction. The solid sulbactam is directly prepared during the reaction preparation process without separation, thus the method is simple to operate and easy for industrial production; the method adopts single-bromination reaction to substitute double-bromination reaction; moreover, bromine which has greater pollution is not used as a raw material, but hydrobromic acid is taken as a raw material, and the method is simple to operate and is low in cost; and the sulbactam solid which is prepared through the method is high in yield and good in quality.

The invention discloses a synthetic method of salbactam acid. The synthetic method comprises the following steps: carrying out diazotized bromination reaction on 6-aminopenicillanic acid to form bromopenicillanic acid; and then, carrying out oxidation reaction and reduction reaction to obtain salbactam acid, wherein in the diazotized bromination reaction, 6-aminopenicillanic acid is continuously added in form of an acidic solution, the acidic solution of 6-aminopenicillanic acid is 5-8% sulfuric acid aqueous solution, 13-15% hydrobromic acid aqueous solution or 5-8% hydrochloric acid aqueous solution. 6-aminopenicillanic acid is dropwise added in form of the acidic solution, so that dust pollution is avoided and the work environment of field personnel is improved. Meanwhile, 6-aminopenicillanic acid exists in form of stable salt, decomposition reaction is avoided, and the reaction quality is improved. The three-step yield of the method is over 70%, the HPCL purity is over 99.7%, the individual impurity content is less than 0.1% and the total impurity content is less than 0.5%.

Synthesis of cloxacillin benxethine is carried out by: dissolving 6-aminopenicillanic acid in aqueous organic solvent to form a sodium salt, condensing with o-chlorbenzylisoxazoleacyl cyanide to obtain cloxacillin benxethine solution directly, and having metathesis with N,N-dibenzyl quadol diacetate. It is simple and costs low.

The invention discloses a penicillin fermentation broth treating technology, which comprises the following steps of: cooling an original penicillin fermentation broth, filtering the cooled penicillin fermentation broth by a closed ceramic-membrane cross-flow filtration system, and collecting high-titer ceramic-membrane filtrate; during filtration, when the wet solid content in the penicillin fermentation broth is enhanced to 1.8-2 times that of the original fermentation broth, adding water with weight accounting for 2 times that of the original fermentation broth for dialyzing to obtain and collect low-titer ceramic-membrane filtrate, and then nano-filtering, concentrating and dewatering the low-titer ceramic-membrane filtrate for later use; continuing to add water with weight accounting for 2 times that of the original fermentation broth for dialyzing to obtain and collect ultra-low-titer ceramic-membrane filtrate; stopping filtration until the titer of penicillin in the penicillin fermentation broth is low to 500-800U; collecting bacterium dregs intercepted by the ceramic-membrane filtration system; putting the high-titer ceramic-membrane filtrate in 6APA (6-aminopenicillanic acid) for conversion or oxidization, ring enlargement and cracking, thus preparing 7-ADCA (7-aminodeacetoxy cephalosporanic acid); and collecting the obtained bacterium dregs and adding engineering bacteria for decomposing the bacterium dregs.

The invention provides a preparing method for D(-)-sulbenicillin disodium. The preparing method includes the concrete operation steps that D(-)-sulfophenylacetic acid, dichloroethane and a catalyst dimethylformamide are added into a reaction container, a BTC/C2H4Cl2 solution serves as an acylating chlorination agent, and a dichloroethane solution of D(-)-sulfophenylacetyl chloride is obtained through preparation; D(-)-sulfophenylacetyl chloride and 6-aminopenicillanic acid are prepared into D(-)-sulbenicillin disodium through condensation and refining. The BTC/C2H4Cl2 solution is adopted as the acylating chlorination agent, reaction efficiency is high, the number of side reactions is small, sulfur dioxide pollution is avoided, and the preparing method is of significance in environment-friendly production; acetone and 75% ethyl alcohol are adopted as solvent in the condensation reaction, the pH value is controlled to be seven through trimethylamine, the condensation reaction is carried out at about 10 DEG C, reaction conditions are moderate, the process is simple and easy to operate, the purity and the yield of the obtained D(-)-sulbenicillin disodium are high, and the preparing method is suitable for industrial production.

The invention relates to the field of medicine synthesis and provides a synthesis method of sulbactam acid, aiming at the problem of low yield of a traditional synthesis manner. The synthesis method comprises the following steps: S1, carrying out diazotization and bromination reaction: adding bromine, a dilute sulfuric acid solution and a sodium nitrite solid into 6-aminopenicillanic acid, whereinthe concentration of the dilute sulfuric acid solution is 20 to 25 percent; reacting to obtain a first intermediate; S2, carrying out oxidization reaction: dropwise adding potassium permanganate andthe dilute sulfuric acid solution into the first intermediate, wherein the concentration of the dilute sulfuric acid solution is 20 to 25 percent; S3, carrying out hydrogenation reaction: dropwise adding zinc powder and the dilute sulfuric acid solution into a second intermediate and reacting to obtain the sulbactam acid. The dilute sulfuric acid solution with the concentration of 20 to 25 percentis used for reacting, which facilitates the improvement of the activity of the diazotization and bromination reaction and the oxidization reaction, and reactants are enabled to react more completely,so that the improvement of the yield of the diazotization and bromination reaction and the oxidization reaction is facilitated, and the total yield of the reaction is further improved.