48 results about "Gentamicin C1a" patented technology

The invention provides a preparation method for gentamicin C1a. The preparation method comprises the following steps: performing the microwave mutagenesis and chemical mutagenesis to gentamicin B producing bacteria, selecting a new bacterial strain in which the gentamicin C1a is the main component, performing the microwave mutagenesis firstly and performing the chemical mutagenesis secondly to obtain the producing bacteria of the gentamicin C1a, performing the fermenting cultivation, separating the obtained fermentation liquor through a micro-filtration membrane, an ultra-filtration membrane and a nano-filtration membrane so as to obtain a crude product of the gentamicin C1a. The yield of the gentamicin C1a is very stable through the continuous passage of the producing bacteria of the obtained gentamicin C1a, the production cost is lower, and the preparation method is suitable for the industrialization application.

The invention relates to a synthesis method of 6''-N-ethyl gentamicin C1a. The synthesis method of the 6''-N-ethyl gentamicin C1a comprises the following steps that (1) a compound 1 gentamicin C1a isdissolved in a solvent for cooling, BOC-ON is added and stirred, and water and ethyl acetate are added to be subjected to liquid separating, water phase taking, and condensing to obtain a compound 2;(2) a concentrated solution is dissolved by methanol, triethylamine is added for cooling, and acetic anhydride is added, stirred and condensed to remove a solvent; (3) hydrochloric acid is added to aconcentrated solution, and stirred at the room temperature, pH is adjusted by a sodium hydroxide solution for concentration, and a compound 3, namely 1,3,2''-N,N,N-triacetyl gentamicin C1a is obtainedby purification and separation through a silica gel column; and (4) after the 1,3,2''-N,N,N-tracetyl gentamicin C1a, glycol dimethyl ether, hexamethyldisilazane and a concentrated sulfuric acid are mixed and heated until refluxing and dissolving, stirring and concentrating continue to be conducted to remove the solvent so as to obtain a compound 4, dichloromethane is added for cooling, acetaldehyde is added to be stirred, potassium borohydride is added to be stirred, a borate buffer solution is added to be stirred, sodium hydroxide is added for condensing and removing the dichloromethane, thesodium hydroxide is added for heating and refluxing, and macroporous resin is subjected to desalination and separation to obtain a compound 5, namely 6''-N- ethyl gentamicin C1a.

The invention discloses a method for detecting gentamicin C1a, wherein the method comprises the following steps: mixing a to-be-detected sample containing gentamicin C1a with a derivatization reagent evenly and carrying out a derivatization reaction, and then detecting by using a liquid chromatography or liquid chromatography-mass spectrometry detection method. The derivatization reagent contains several components of a solvent, 1,2-phthalic dicarboxaldehyde, mercaptoacetic acid and a buffer solution; the molar ratio of 1,2-phthalic dicarboxaldehyde to mercaptoacetic acid in the derivatization reagent is 1:3.8-1:0.5; the pH of the derivatization reagent is 10-11; the ratio of the molar amount of 1,2-phthalic dicarboxaldehyde in the derivatization reagent to the molar amount of gentamicin C1a detected in the to-be-detected sample in a single detection result is greater than or equal to 3.59. The method for detecting gentamicin C1a has the advantages of simple operation, and relatively high accuracy and wide linear range in detection of the gentamicin C1a concentration in production samples.

The invention discloses a synthetic method of etimicin sulfate. The synthetic method comprises the following steps: carrying out a reaction on gentamicin C1a, zinc acetate and acetic anhydride to obtain 3, 2', 6'-tri(N-acetyl) gentamicin C1a; after separating and purifying the 3, 2', 6-tri(N-acetyl) gentamicin C1a, carrying out a reaction with iodoethane to obtain 3, 2', 6'-tri(N-acetyl)-1-ethyl gentamicin C1a; hydrolyzing the 3, 2', 6'-tri(N-acetyl)-1-ethyl gentamicin C1a by sodium hydroxide to obtain an aqueous solution of etimicin sulfate; and carrying out HZD-2 macroporous resin adsorption, separation and purification, concentration, sulfate formation, decarburization and drying on the aqueous solution of etimicin sulfate to obtain an etimicin sulfate finished product. The method disclosed by the invention is high in yield which is 55%, and satisfies the requirements of Chinese pharmacopoeia (Edition 2010).

The invention relates to a continuous separation and purification technology of gentamycin C1a. Efficient separation of a gentamycin C1a recovered liquid is realized through using a continuous chromatographic separation technology. The technology comprises the following steps: allowing recovered gentamycin C1a to enter a continuous chromatographic system, adsorbing, washing out impurities, eluting, collecting the obtained eluate, regenerating a chromatographic column, and concentrating the collected eluate to obtain gentamycin C1a. The gentamycin C1a separated in through the technology has the advantages of high yield and high purity, so the technology has the advantages of low cost, environmental protection and suitableness for industrial production.

The invention discloses an etimicin sulfate preparation method. The etimicin sulfate preparation method includes the steps of protecting amino groups at 3, 2', 6' and 3' of gentamicin C1a with Fmoc-Cl and performing purification and evaporation to dryness to obtain quadrifluorenyl methoxycarbonyl gentamicin C1a; adding N-ethyl of an acetaldehyde aqueous solution under acidic conditions and performing reduction with sodium triacetoxyborohydride; finally adding a piperidine / DMSO (dimethylsulfoxide) solution for deprotection; performing secondary purification on an reaction solution with weakly acidic cation adsorption resin after performing primary purification on the reaction solution with a macroporous adsorption resin column and adding sulfuric acid to a purified product to obtain etimicin sulfate through reaction. The etimicin sulfate preparation method is high in selectivity and less in side reaction in group protecting, mild in reaction conditions, simple in operation and easy to perform industrial production during the whole reaction process and high in purity and yield of the product. (An equation as shown in the description).

The invention discloses a method for preparing 3,2',6'-tri-N-acetyl gentamicin C1a, which comprises the following steps of: (1) performing coordination reaction on gentamicin C1a and zinc acetate in a methanol solvent at the temperature of between 15 and 25 DEG C to prepare a gentamicin C1a-Zn complex; (2) reducing the temperature of the system of the step (1) to between 0 and 10 DEG C, dropwise adding mixed liquid consisting of acetic anhydride, triethylamine and tetrahydrofuran with stirring for acylation reaction to prepare 3,2',6'-tri-N-acetyl gentamicin C1a-Zn complex, after dropwise adding, continuously stirring and reacting for 1 to 2 hours, and adding water and distilling under reduce pressure to prepare concentrated solution containing the 3,2',6'-tri-N-acetyl gentamicin C1a-Zn complex; and (3) performing after treatment on the concentrated solution prepared by the step (2) to prepare a 3,2',6'-tri-N-acetyl gentamicin C1a finished product. The method has the advantage of higher yield.

The invention discloses a preparation method of 1-N-ethyl gentamicin C1a sulfate. The method comprises the following steps of: carrying out a complexation reaction on gentamicin C1a and zinc acetate in a methanol solvent; then, dropping a mixed solution of acetic anhydride, triethylamine and tetrahydrofuran to carry out an acylation reaction and obtaining 3,2',6'-3-N-acetyl-gentamicin C1a by post-treatment; then, carrying out a silylation reaction with hexamethyl disilazane in a chloroform solvent; carrying out an N-alkylation reaction with acetaldehyde in a carrene solvent; then, carrying out a reduction reaction with potassium borohydride; hydrolyzing with an NaOH solution; obtaining 1-N-ethyl gentamicin C1a by post-treatment; adding the 1-N-ethyl gentamicin C1a to anhydrous ethanol or anhydrous methanol for stirring or dissolving; then, dropping concentrated sulfuric acid; and obtaining 1-N-ethyl gentamicin C1a sulfate by post-treatment. The method of the invention has higher yield.

The invention discloses a preparation method of 1-N-ethyl gentamicin Cla, which comprises the following steps of: reacting 3,2',6'-tri-N-acetyl gentamicin Cla with hexamethyldisilazane in a trichloromethane solvent under the catalysis of concentrated sulfuric acid to generate 3,2',6'-tri-N-acetyl-5,2'',4''-tri(trimethylsilyl) gentamicin Cla; carrying out N-alkylation reaction on the 3,2',6'-tri-N-acetyl-5,2'',4''-tri(trimethylsilyl) gentamicin Cla and acetaldehyde in a dichloromethane solvent at a temperature of 8-12 DEG C; carrying out reduction reaction with potassium borohydride; then hydrolyzing with an NaOH solution to obtain hydrolyzate of the 1-N-ethyl gentamicin Cla; and post-processing the hydrolyzate to obtain a finished product of the 1-N-ethyl gentamicin Cla. The method has the advantage of higher yield of the1-N-ethyl gentamicin Cla.

The invention relates to a preparation method of 1-N-ethyl gentamicin C1a. The method comprises the following steps: under the condition of 18-20 DEG C, slowly adding sodium borohydride into three flasks with trichloromethane and glacial acetic acid, dissolving 3,2',6'-tri-N-gentamicin C1a into trichloromethane, slowly adding the mixture into the flasks through a constant pressure dropping funnel, keeping the temperature to 40-50 DEG C, vigorously stirring for reaction 20 hours, cooling and adding a saturated sodium hydroxide aqueous solution to neutralize the system, diluting with ethyl alcohol, extracting with trichloromethane, performing vacuum concentration to obtain the oily matter, and adding a 1N sodium hydroxide aqueous solution for circulation reflux for 24 hours; diluting with salt-free water, performing column chromatography isolation, collecting effective constituents, concentrating and freeze-drying to obtain 1-N-ethyl gentamicin C1a.